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Purpose: Non-alcoholic steatohepatitis (NASH) is an inflammatory disorder and an aggressive form of fatty liver disease. Certain microRNAs, including miR-122, 21, 34a, and 451, are involved in the transition from steatosis to NASH. This study examined how trans-chalcone (the core of chalcone derivatives) affects NAFLD progression by regulating miRNAs. Methods: Male rats were divided into three groups (n = 7/group) as follows: control, rats were gavaged with 10% tween 80 (for two weeks); NASH, rats were gavaged with a high-fat liquid diet (HFD; for six weeks) and 10% tween 80 (for two weeks); NASH + Chal, rats were gavaged with the HFD (for six weeks) and trans-chalcone (for two weeks). Hepatic expression levels of miR-122, 21, 34a, and 451 were determined. Results: trans-Chalcone reversed histological abnormalities, reduced liver injury markers, and attenuated insulin resistance in HFD-fed rats. In the liver, HFD-induced NASH increased the expression level of miR-34a and decreased expression levels of miR-122, 21, and 451. However, trans-chalcone inhibited HFD-induced changes in expression levels of these miRNAs. Conclusion: trans-Chalcone could inhibit the transition from steatosis to NASH through the modulation of miR-122, 21, 34a, and 451 expression levels in the liver.

Background: Learning and memory may decline due to Alzheimer’s disease (AD) in older adults. A reduction in cyclic guanosine monophosphate concentration and an increase in phosphodiesterase activity have been reported in the process of aging. Although phosphodiesterase (PDE) type 5 inhibitor, Tadalafil is used to treat erectile dysfunction; PDE inhibitors possibly prevent cognition impairment in aging. This study was designed to investigate the effects of tadalafil on memory in middle-aged and young healthy and AD rats. Methods: Memory impairment was induced by intracerebroventricular (ICV) administration of streptozotocin (STZ; 3 mg/kg) in AD rats. Male Wistar rats (middle-aged and young) were distributed into six groups as follows: two control, two AD, and two AD+tadalafil (1 mg/kg) groups. Saline or tadalafil was administered once a day orally for 40 consecutive days. Animals were tested using novel object recognition (NOR), passive avoidance learning (PAL), and Morris water maze (MWM) tests. Results: Aged AD rats exhibited a significant impairment in cognition in the NOR test and impaired learning and memory in PAL and MWM tests compared with the control aged rats. Tadalafil treatment in aged AD rats significantly improved the discrimination index in the NOR test, decreased the time spent in the dark compartment in the PAL test, and increased time spent in the target quadrant in MWM tests compared with aged AD rats. In young AD rats, treatment with tadalafil significantly enhanced cognition, learning, and memory in the NOR, PAL, and MWM tests compared with young AD rats treated with saline. Conclusion: Tadalafil treatment in aged rats improves cognition and memory after STZ-induced (ICV) memory impairment. It can be concluded that chronic treatment with tadalafil is protective against cognitive, learning, and memory impairment in both young and aged subjects.

Traumatic brain injury (TBI) causes acute and lasting impacts on the brain, driving pathology along anatomical, cellular, and behavioral dimensions. Rodent models offer an opportunity to study the temporal progression of disease from injury to recovery. Transcriptomic and epigenomic analysis were applied to evaluate gene expression in ipsilateral hippocampus at 1 and 14 days after sham (n = 2 and 4, respectively per time point) and moderate lateral fluid percussion injury (n = 4 per time point). This enabled the identification of dynamic changes and differential gene expression (differentially expressed genes; DEGs) modules linked to underlying epigenetic response. We observed acute signatures associated with cell death, astrocytosis, and neurotransmission that largely recovered by 2 weeks. Inflammation and immune signatures segregated into upregulated modules with distinct expression trajectories and functions. Whereas most down-regulated genes recovered by 14 days, two modules with delayed and persistent changes were associated with cholesterol metabolism, amyloid beta clearance, and neurodegeneration. Differential expression was paralleled by changes in histone H3 lysine residue 4 trimethylation at the promoters of DEGs at 1 day post-TBI, with the strongest changes observed for inflammation and immune response genes. These results demonstrate how integrated genomics analysis in the pre-clinical setting has the potential to identify stage-specific biomarkers for injury and/or recovery. Though limited in scope here, our general strategy has the potential to capture pathological signatures over time and evaluate treatment efficacy at the systems level.

Developing mammals are exposed to progesterone through several sources; however, the role of progesterone in early development is not well understood. Males express more progestin receptors (PRs) than females within several brain regions during early postnatal life, suggesting that PRs may be important for the organization of the sex differences in the brain and behavior. Indeed, previous studies showed cognitive impairments in male rats treated neonatally with a PR antagonist. In the present study, we examined the role of PRs in organizing juvenile behaviors. Social play behavior and social discrimination were examined in juvenile male and female rats that had been treated with CDB, a PR antagonist, during the first week of postnatal life. Interestingly, neonatal PR antagonism altered different juvenile behaviors in males and females. A transient disruption in PR signaling during development had no effect on social discrimination but increased play initiation and pins in females. These data suggest that PRs play an important role in the organization of sex differences in some social behaviors.

Neurotoxicity is a principal concern in nonclinical drug development. However, standardized and universally accepted fluid biomarkers for evaluating neurotoxicity are lacking. Increasing clinical evidence supports the potential use of neurofilament light (NfL) chain as a biomarker of several neurodegenerative diseases; therefore, we investigated changes in the cerebrospinal fluid (CSF) and serum levels of NfL in Sprague Dawley rats treated with central nervous system (CNS) toxicants (trimethyltin [TMT, 10 mg/kg po, single dose], kainic acid [KA, 12 mg/kg sc, single dose], MK-801 [1 mg/kg sc, single dose]), and a peripheral nervous system (PNS) toxicant (pyridoxine, 1200 mg/kg/day for 3 days). Animals were euthanized 1 (day 2), 3 (day 4), or 7 days after administration (day 8). Increased serum NfL was observed in TMT- and KA-treated animals, which indicated neuronal cell death in the brain on days 2, 4, and/or 8. MK-801-treated animals exhibited no changes in the serum and CSF levels of NfL and no histopathological changes in the brain at any time point. Pyridoxine-induced chromatolysis of the dorsal root ganglion on day 2 and degeneration of peripheral nerve fiber on day 4; additionally, serum NfL was increased. A strong correlation was observed between the serum and CSF levels of NfL and brain lesions caused by TMT and KA, indicating that NfL could be a useful biomarker for detecting CNS toxicity. Additionally, PNS changes were correlated with serum NfL levels. Therefore, serum NfL could serve as a useful peripheral biomarker for detecting both CNS and PNS toxicity in rats.

Background/aim In this study, we aimed to investigate the effects of antioxidant iloprost (ILO) and ß3 adrenergic receptor agonist (BRL) on transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential canonical 1 (TRPC1) ion channels on an experimental ischemia and reperfusion injury model in 30 male Wistar albino rats aged 8–10 weeks. Materials and methods Wistar Albino rats aged were divided into 5 equal groups. Group I Sham operation, Group II IR (ischemia-reperfusion) procedure, Group III IR + intravenous ILO administration, Group IV IR + intraperitoneal BRL administration, and Group V IR + intravenous ILO + intraperitoneal BRL administration group. Two ng/kg/min ILO intravenous infusion was applied to the ILO group. A single dose of 5 mcg/kg BRL intraperitoneal was applied to BRL group. TOS (total oxidant status), TRPA1, and TRPC1 levels were measured with ELISA (enzyme linked immunosorbent assay) in serum, immunohistochemical staining in musculus quadriceps femoris tissue. Results Compared with the sham group, the IR group had a statistically significant increase in serum levels of TOS (p = 0.004), TRPA1 (p = 0.002), and TRPC1 (p = 0.008) along with TRPA1- and TRPC1-immunoreactivity (p = 0.005, each) in the tissue. When compared with the IR group in terms of serum levels of TRPA1 and tissue TRPA1-immunoreactivity, although there was no statistically significant difference in the IR+Ilo (p = 0.257 and p = 0.429, respectively), IR+Brl (p = 0.024 and p = 0.177, respectively), and IR+Ilo+Brl (p = 0.024 and p = 0.329, respectively) groups, serum levels of TOS and TRPC1 along with tissue TRPC1-immunoreactivity were statistically significantly reduced in the IR+Ilo (p = 0.002, p = 0.008, and p = 0.004, respectively), IR+Brl (p = 0.004, p = 0.008, and p = 0.004, respectively), and IR+Ilo+Brl groups (p = 0.002, p = 0.008, and p = 0.004, respectively). Conclusion In IR group serum TOS, TRPA1 and TRPC1 levels ,and tissue TRPA1 and TRPC1 immunoreactivity were statistically significant increase when compared to the sham group. In IR+ILO, IR+BRL and IR+ILO+BRL groups serum TRPA1 and tissue TRPA1 immunoreactivity did not change when compared to IR group. Serum TOS and TRPC1 levels, tissue TRPC1 immunoreactivty were statistically significant decreased when compared to IR group. More detailed and expanded population studies are needed to discuss our results.

Made available in DSpace on 2022-04-28T17:22:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-10-20 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) We evaluated the influence of the hyperglycemic intrauterine environment and postweaning consumption of a high-fat diet (HFD) on the glycemia, insulin, lipid, and immunological profile of rat offspring in adulthood. Female rats received citrate buffer (Control-C) or Streptozotocin (a beta cell-cytotoxic drug to induce diabetes-D) on postnatal day 5. In adulthood, these rats were mated to obtain female offspring, who were fed a standard diet (SD) or HFD from weaning to adulthood (n = 10 rats/group). OC/SD and OC/HFD represent female offspring of control mothers and received SD or HFD, respectively; OD/SD and OD/HFD represent female offspring of diabetic mothers and received SD or HFD, respectively. At adulthood, the oral glucose tolerance test (OGTT) was performed and, next, the rats were anesthetized and euthanized. Pancreas was collected and analyzed, and adipose tissue was weighted. Blood samples were collected to determine biochemical and immunological profiles. The food intake was lower in HFD-fed rats and visceral fat weight was increased in the OD/HFD group. OC/HFD, OD/SD, and OD/HFD groups presented glucose intolerance and lower insulin secretion during OGTT. An impaired pancreatic beta-cell function was shown in the adult offspring of diabetic rats, regardless of diet. Interleukin (IL)-6 and IL-10 concentrations were lower in the OD/HFD group and associated to a low-grade inflammatory condition. The fetal programming was responsible for impaired beta cell function in experimental animals. The association of maternal diabetes and postweaning HFD are responsible for greater glucose intolerance, impaired insulin secretion and immunological change. Summary sentence Summary Sentence The association of maternal diabetes and postweaning HFD causes glucose intolerance due to beta-cell disarrangement and impaired insulin secretion, and immunological changes in adult offspring. SJo Paulo State Univ UNESP, Botucatu Med Sch, Lab Expt Res Gynecol & Obstet, Tocogynecol Postgrad Course, Botucatu, SP, Brazil Fed Univ Mato Grosso UFMT, Inst Biol & Hlth Sci, Lab Syst Physiol & Reprod Toxicol, Barra Do Garcas, MT, Brazil Fed Univ Maranhao UFMA, Dept Physiol Sci, Lab Expt Physiol, Sao Luis, MA, Brazil Univ Estadual Paulista UNESP, Botucatu Med Sch, Res Support Off, Botucatu, SP, Brazil SJo Paulo State Univ UNESP, Botucatu Med Sch, Lab Expt Res Gynecol & Obstet, Tocogynecol Postgrad Course, Botucatu, SP, Brazil Univ Estadual Paulista UNESP, Botucatu Med Sch, Res Support Off, Botucatu, SP, Brazil FAPESP: 2016/25207-5

We aimed to assess the effects of dexmedetomidine (DEX) on postoperative cognitive function of sleep deprivation (SD) rats based on changes in inflammatory response. Male rats were randomly divided into blank control (C), SD, DEX, and SD+DEX groups. The SD model was established through intraperitoneal injection of DEX. The escape latency was detected through Morris water maze test daily, and the mechanical withdrawal threshold and thermal withdrawal latency were detected for 8 d. The content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) in hippocampus homogenate were determined, and the morphological changes in neurons were detected through Nissl staining. The concentration of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6 in the hippocampus was detected by enzyme-linked immunosorbent assay, and the Rac1/protein kinase B (AKT)/nuclear factor-κB (NF-κB) expressions were detected by Western blotting. The changes in immunofluorescence localization of NF-κB were observed by confocal microscopy. Compared with SD group, the escape latency was shortened, original platform-crossing times increased, MDA content declined, SOD activity rose, neurons were arranged orderly and number of Nissl bodies increased in the hippocampal CA1 region, levels of IL-1β, TNF-α, and IL-6 in the hippocampus decreased, Rac1/AKT/NF-κB expressions were down-regulated, and proportion of NF-κB entering the nucleus declined in SD+DEX group (P

Trichosomoides crassicauda (T. crassicauda) is a parasite commonly localized in the urinary bladder (UB) of laboratory and wild rats. The presence of these helminths can influence the prediction of pathological changes in the UB. Therefore, the purpose of this research was to make a comprehensive study of the features of the morphological changes in the UB wall of white laboratory rats as a result of T. crassicauda infestation. The study was performed on male rats using histological (Hematoxyline-Eosin and Alcian Blue staining) and immunohistochemical (Ki-67, Hsp70, Hsp90α, CD3 and CD20) methods. T. crassicauda was detected in both urine and UB samples. Morphological changes were observed as disruption in urothelial cell stratification and insignificant proliferative and immune responses in the UB. Increased heat shock protein levels were observed which may suggest a natural body’s resistance to this parasite.

Background and aims: The abnormal increase in blood cholesterol can cause many problems. Statins have a cholesterol-lowering effect, but they also have adverse effects. Garlic prevents the formation of cholesterol due to its antibiotic properties. This study aimed to investigate the comparative effect of garlic powder and atorvastatin on hypercholesterolemia-induced reproductive failure in female rats. Methods: In the present experimental study, 48 adult female Wistar rats were divided into eight groups (n=6), including control, atorvastatin (10 mg/kg/d; orally), atorvastatin (20 mg/kg/d; orally), garlic powder (100 mg/kg/d; orally), hypercholesterolemia (1.5 mg/kg/d of cholesterol; orally), hypercholesterolemia + atorvastatin (10 mg/kg/d), hypercholesterolemia + atorvastatin (20 mg/kg/d), and hypercholesterolemia + garlic powder. After 30 days, rats were euthanized and blood samples were obtained from their heart for serological assessments. The right ovary was transferred to 10% formalin for histological analyses, and the left ovary was transferred to a −80°C freezer for evaluation of oxidative stress markers. Data were statistically analyzed by ANOVA and Tukey’s test using SPSS version 24.0 (P

Purpose The aim of this study was to investigate the effect of clozapine use on bone tissue by applying computerized tomography, dual-energy X-ray absorptiometry, and histological and biomechanical analyses in an experimental rat model. Methods Sixteen female Wistar Albino rats were included in this study. These animals were divided into two groups: the control group and the clozapine group. The animals in the clozapine group received 10 mg/kg clozapine, and the animals in the control group received tap water by oral gavage daily for 28 days. After sacrification, the femurs of the rats were used for radiologic, histologic, dual-energy X-ray absorptiometry, and biomechanical evaluations. Results Although the mean values of the clozapine group were higher in terms of histological, bone mineral density, and biomechanical evaluations, the statistical analyses were not significantly different. Conclusion Clozapine use did not affect bone density in the rats. Clozapine can be the preferred treatment for patients with schizophrenia to avoid osteoporosis. It will be necessary to conduct further long-term follow-up and controlled studies in animals and humans to confirm these findings.

Outward remodeling of the maternal uterine circulation during pregnancy is essential for normal uteroplacental perfusion and pregnancy outcome. The physiological mechanism by which this process is regulated is unknown; we hypothesized that it involved the normalization of wall shear stress (WSS). Pregnant Sprague–Dawley rats underwent unilateral ligation of the main uterine artery and vein at the cervical end of the uterus on gestational day 10, thus restricting inflow/outflow of blood into that uterine horn to a single point at the ovarian end; the contralateral sham‐operated side provided an internal control. This procedure alters uterine hemodynamics by increasing WSS, since the entire uterine horn is supplied by one rather than two vessels. Arterial diameter and blood flow velocity values were measured by intravital ultrasonographic pulse‐wave Doppler on gestational day 20 and used to calculate WSS. Although both ovarian artery lumen diameter and blood velocity increased, WSS was similar in both horns. These data support the concept that increased WSS secondary to hemochorial placentation is the primary physiological stimulus for uterine vascular remodeling and that its normalization may be the primary mechanism that regulates the extent of arterial circumferential growth required to maintain placental perfusion. We further hypothesize that shallow spiral artery invasion, such as occurs in preeclampsia, limits the increase in upstream shear stress and results in attenuated remodeling and placental under‐perfusion.

Background Endometriosis can lead to infertility. Since there is no definitive treatment for endometriosis, animal modelling seems necessary to examine the possible treatments. Mouse endometrium cannot be separated for endometriosis induction. In addition, transplantation of uterus into the abdominal viscera to induce endometriosis causes organ damage. In this study, we defined a new model of endometriosis leading to separability of endometrium and a safe anatomical region for transplantation. Methods Forty female mice were allocated to 5 groups: 1, sham; 2, allograft uterus transplantation of mice to anterior abdominal wall of mice; 3, allograft uterus transplantation of mice to mesentery of mice; 4, xenograft endometrial transplantation of rat to anterior abdominal wall of mice; 5, xenograft endometrial transplantation of rat to mesentery of mice. Adult female rats with a previous pregnancy experience were selected and placed in the vicinity of male rats for 2 weeks to induce estrogen secretion and increase endometrial thickness. Results In the 4th group of animals, compared to sham, the peritoneal concentrations of VEGF‐A, TNF‐α, NO, MDA, and serum levels of CA‐125 and IL‐37 were increased and total body weight was decreased, while weight and size of endometrial lesions were increased significantly (P, In this new model of animal endometriosis, the rat uterus was dissected and grafted to the anterior abdominal wall of mice. The general principles of this method were hormonal and estrous synchronization in transplanted rats and recipient mice, which led to high levels of estrogen secretion in both donor and recipient species. Thus, the thickened endometrial layer in rats was dissected easily and successfully was transplanted and implanted recipient mice. 4 weeks later, all histological, genetic and biochemical factors associated with endometriosis were expressed in transplant recipients.

Objective: To determine the effect of noise stress on Thyroid Stimulating Hormone in adult rats. Study Design: Laboratory-based experimental study. Place and Duration of Study: Department of Anatomy Army Medical College, Rawalpindi in collaboration with National Institute of Health, Islamabad, from Jan to Dec 2020. Methodology: A total of 30 adult Sprague Dawley rats were distributed into three groups as ten rats/group. Group A served as the control group, rats in group B were exposed to 100 dB noise for continuous 4 hours/day for four months, and the rats in group C were exposed to 100 dB noise for continuous 6 hours/day for four months. At the end of the study, serum samples were collected from the rats’ tail veins. Thyroid-stimulating hormone levels were compared among the groups. Results: At the start of the study, mean serum thyroid stimulating hormone level of control group A rats was 0.34 ± 0.15 µIU/ml. Mean serum thyroid stimulating hormone level of experimental groups B and C rats at the start of the study was 0.46 ± 0.18 µIU/ml and 0.41 ± 0.14 µIU/ml, respectively Mean serum thyroid stimulating hormone of rats did not differ statistically significantly between the group p=0.26, By the end of study mean serum thyroid stimulating hormone level of control group. A rats was 0.6 ± 0.2 µIU/ml. Mean serum thyroid stimulating hormone levels of experimental groups B and C rats at the end of the study were 1.32 ± 0.35 µIU/ml and 1.86 ± 0.67 µIU/ml, respectively.......

Objective: Hypertension is a major risk factor for cardiovascular disease, kidney disease, and premature death. Increased levels of creatine kinase are associated with development of hypertension. However, it is unknown if creatine, a substrate of CK, is associated with the development of hypertension. We therefore, aimed to investigate the association between plasma creatine concentration and incident hypertension. Methods: We measured fasting plasma creatine concentrations by nuclear magnetic resonance spectroscopy in participants of the population-based PREVEND study. The study outcome was incident hypertension, defined as either a SBP of at least 140mmHg, a DBP of at least 90mmHg, or the new usage of antihypertensive drugs. Participants with hypertension at baseline were excluded. Results: We included 3135 participants (46% men) aged 49=10years. Mean plasma creatine concentrations were 36.2=17.5mmol/l, with higher concentrations in women than in men (42.2=17.6 versus 29.2=17.6mmol/l; P, Journal of Hypertension, 40 (2)

SUMMARY: Anti-Müllerian hormone (AMH) and Inhibin B (INHB) in the glycoprotein structure are members of the transforming growth factor β family and expressed by granulosa cells from puberty. AMH is a factor that increases the life span of small developing follicles. For this reason, it is widely used to determine the ovarian reserve and age. Inhibin-B secreted from granulosa cells plays a role in regulation of the Follicle Stimulating Factor (FSH) and determination of the follicle diameter. There are few studies on the effect of these two age-related hormones on ovarian histology in rats. In this study, AMH and INHB expression in ovarian tissues of female rats of different age groups, their relationship with ovarian structure and folliculogenesis were examined histologically and biochemically. Wistar Albino rats were used in the study and a total of 3 groups were formed. The ovaries of rats in the pre-oestrous period were collected, and follicle count was performed on tissue sections in batches. Expression of AMH in the follicles was identified immunohistochemically. In serum, AMH and INHB levels were assessed by ELISA method and their significance was evaluated statistically. Results from light microscopic examination determined that AMH was expressed from the granulosa cells of developing follicles. INHB expression during the prepubertal period and AMH had a protective effect on the ovarian reserve and the number of developing follicles, respectively.

Spontaneous recovery of lost motor functions is relative fast in rodent models after inducing a very mild/moderate spinal cord injury (SCI), and this may complicate a reliable evaluation of the effectiveness of potential therapy. Therefore, a severe graded (30 g, 40 g and 50 g) weight-compression SCI at the Th9 spinal segment, involving an acute mechanical impact followed by 15 min of persistent compression, was studied in adult female Wistar rats. Functional parameters, such as spontaneous recovery of motor hind limb and bladder emptying function, and the presence of hematuria were evaluated within 28 days of the post-traumatic period. The disruption of the blood-spinal cord barrier, measured by extravasated Evans Blue dye, was examined 24 h after the SCI, when maximum permeability occurs. At the end of the survival period, the degradation of gray and white matter associated with the formation of cystic cavities, and quantitative changes of glial structural proteins, such as GFAP, and integral components of axonal architecture, such as neurofilaments and myelin basic protein, were evaluated in the lesioned area of the spinal cord. Based on these functional and histological parameters, and taking the animal’s welfare into account, the 40 g weight can be considered as an upper limit for severe traumatic injury in this compression model.

Ivasivka Khrystyna. Dynamics of changes in the structural components of the mucosa and cartilage of the larynx of rats at the end of 42 days of experimental opioid exposure and after 56 days with opioid withdrawal. Journal of Education, Health and Sport. 2021;11(07): 201-218. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2021.11.07.019 https://apcz.umk.pl/czasopisma/index.php/JEHS/article/view/JEHS.2021.11.07.019 https://zenodo.org/record/5156375 The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019. © The Authors 2021; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 25.06.2021. Revised: 12.07.2021. Accepted: 29.07.2021. UDC: 611. 321 - 018.3⁄. 73: 615.214.24.035.8] .08 Dynamics of changes in the structural components of the mucosa and cartilage of the larynx of rats at the end of 42 days of experimental opioid exposure and after 56 days with opioid withdrawal Khrystyna Ivasivka Danylo Halytsky Lviv National Medical University Applicant of the Department of Normal Anatomy https://orcid.org/0000-0003-4372-225х Abstract In our work we aimed to study the pathomorphological manifestations among the structural components of the laryngeal mucosa and cartilage in the later stages of the experimental opioid effect. This goal was achieved through the use of histological techniques to visualize the structural components of the laryngeal mucosa and cartilage. Histological sections with a thickness of 5 -7 mm were made. Histological specimens were prepared according to conventional methods using the dye hematoxylin, eosin, azan according to the method of Heidenhain, PAS-reaction according to Mc-Manus and Alcian blue according to Steedman. Microscopic examinations and photographing of the preparations were performed using an MBI-1 microscope and a Nicon D 3100 digital camera. At the end of 42 days of experimental exposure, the epithelial layer of the epiglottis was inhomogeneously thickened, with excessive accumulation on its pharyngeal and apical part of the stratum corneum. Individual epitheliocytes of the pharyngeal part of the epiglottis underwent necrotic changes, the horny substance loosened in places. On the pharyngeal surface of the mucous membrane found a small amount of mucus with impurities of erythrocytes. Dyscirculatory processes were also registered in the animals of the experimental group. In particular, dilatation and overflow of erythrocytes of vessels of own plate of a mucous membrane of an epiglottis, and also polymorphonuclear infiltration of own plate of a mucous membrane were observed. Key words: opioid; laryngeal mucosa; laryngeal cartilage; rat; early terms

The present study aimed to investigate the protective role of capsaicin in a rat model of 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD)-induced toxicity. Exposure to TCDD which is an environmental toxicant causes severe toxic effects in the animal and human tissues. Therefore, the potential protective effect of capsaicin in TCDD-induced organ damage was investigated in rats by measuring thiobarbituric acid reactive substances (TBARS) level, superoxide dismutase (SOD) activity, and glutathione (GSH) level in the heart, liver, and kidney tissues for oxidant/antioxidant balance. Thirty-two healthy adults (250-300 g weight and 3-4 months old) male Wistar albino rats were randomly distributed into four equal groups (n = 8): Control, CAP, TCDD, TCDD + CAP. A dose of 2 mu g/kg TCDD or a dose of 25 mg/kg capsaicin were dissolved in corn oil and orally administered to the rats for 30 days. The results indicated that TCDD-induced oxidative stress by increasing the level of TBARS and by decreasing the levels of GSH, and SOD activity in the tissues of rats. However, capsaicin treatment was significantly decreased TBARS levels and was significantly increased GSH level and SOD activity (p < 0.05). In addition, capsaicin (25 mg/kg) significantly attenuated TCDD-induced histopathological alteration associated with oxidative stress in the heart, liver, and kidney tissues (p < 0.05). As capsaicin regulates oxidative imbalance and attenuates histopathological alterations in the rat tissues, it may be preventing agents in TCDD toxicity.

A 130-week-old male Royal College of Surgeons rat kept as a non-treated animal in a long-term animal study presented with a mass in the hepatic portal region that adhered to a dilated common bile duct and the duodenum. Histopathologically, the solitary mass showed expansive growth with no apparent compression and continued to dilate the common bile duct, which had a hyperplastic epithelium with intestinal metaplasia. The mass mainly consisted of small to large dilated and/or tortuous ducts with abundant dense connective tissue and many inflammatory cells. The single-layer lining epithelium of the duct changed from cuboidal to columnar. Immunohistochemically, the lining cells were positive for cytokeratin 7, cytokeratin 19, and OV-6, which are bile duct markers. Based on the pathological characteristics, the rat was diagnosed as spontaneous cholangiofibrosis adjacent to a dilated common bile duct with intestinal metaplasia.

Background Cannabidiol (CBD), the non-psychotropic compound from Cannabis sativa, shows positive results on controlling several health disturbances; however, comparable data regarding additional chemical from C. sativa, such as cannabidiolic acid (CBDA), is scarce due to its instability. To address this limitation, a stable CBDA analogue, CBDA methyl ester (HU-580), was synthetized and showed CBDA-like effects. Recently, we described that HU-580 increased wakefulness and wake-related neurochemicals. Objective To extend the comprehension of HU-580´s properties on waking, the c-Fos and NeuN expression in a wake-linked brain area, the hypothalamus was evaluated. Methods c-Fos and NeuN expression in hypothalamic sections were analyzed after the injections of HU-580 (0.1 or 100 μg/kg, i.p.). Results Systemic administrations of HU-580 increased c-Fos and neuronal nuclei (NeuN) expression in hypothalamic nuclei, including the dorsomedial hypothalamic nucleus dorsal part, dorsomedial hypothalamic nucleus compact part, and dorsomedial hypothalamic nucleus ventral part. Conclusion HU-580 increased c-Fos and NeuN immunoreactivity in hypothalamus nuclei suggesting that this drug might modulate the sleep–wake cycle by engaging the hypothalamus.

Zymbal's gland neoplasms are induced in rats through the administration of various carcinogens, but spontaneous neoplasia is rare. This report describes a spontaneous Zymbal's gland carcinoma with lung metastasis found in an aged male Fischer 344 rat. Macroscopically, the dome-like tumor nodule, approximately 30 mm in diameter with ulceration, was located near the ear canal of the rat. No healthy tissue or structure of Zymbal's gland was identified on the corresponding side, while the normal salivary glands and a lacrimal gland were observed. Histologically, a large part of the tumor mass was occupied by poorly differentiated neoplastic cells, the shapes of which were oval to polygonal or fusiform. Additionally, clusters of sebaceous-like foamy cells and squamous metaplasia with prominent keratinization were observed. Tumor cells were found to metastasize to the lung; these cells displayed histological similarities, including a sebaceous gland-like pattern, to those in the primary site. The tumor cells were immunohistochemically positive for cytokeratin AE1/AE3 or vimentin but negative for CD68, S100, α-smooth muscle actin, von Willebrand factor, and desmin. Our results indicate that the tumor was a poorly differentiated Zymbal's gland carcinoma with lung metastasis.

The purpose of this study was to examine the potential effect of Chios Mastic Gum (CMG) consumption on bone mineral density (BMD) and strength of ovariectomized rats. CMG is a known resin used from ancient times for its beneficial biological properties. Thirty mature female Wistar rats were randomized into three equal groups: sham-operated (control), ovariectomized (OVX), and ovariectomized and administered CMG per os (OVX+CMG). BMD of the total tibia, proximal tibia, and the 6th lumbar vertebra were measured at baseline and at 3 and 6 months post ovariectomy. Bone strength was assessed with three-point-bending (3pb) of the right femur. At 3 and 6 months, BMD values of the OVX+CMG group were significantly higher for the anatomical cites evaluated than those of the OVX group. Femoral thickness assessed via 3pb had intermediate values in the treated group compared to the other groups. Cytology of vaginal smears and uterine weight of the OVX+CMG group were consistent with estrogen depletion. Gastrocnemius muscle and intraperitoneal fat ratios to body weight (BW) of the OVX+CMG group did not significantly differ from the control group. Daily consumption CMG had a protective effect on BMD of the total and proximal tibia and the 6th lumbar vertebra of the rats, without causing undesirable effects on the vaginal epithelium and uterus. The 3pb results also demonstrated a favorable effect on the thickness of rat femurs. In addition, CMG was beneficial for both the muscular system and the intraperitoneal fat/BW ratio of the rats.

Hypertension is a chronic disease affecting the whole world due to its clinical effects and complications. The reduction in the release and effect of NO is one of the mechanisms of hypertension formation. Hypertension disrupts the balance between oxidant and antioxidant mechanisms. In this study, we aimed to observe biochemical changes in the blood by treatment propolis, caffeic acid phenethyl ester (CAPE) and pollen in hypertensive rats via Nω-Nitro-L-arginine methyl ester (L-NAME). Rats were divided in five groups. Rats were given L-NAME (40 mg/kg, intraperitoneally) for 14 days to make hypertensive. L-NAME and bee products were administered together with rats for 14 days, then L-NAME for 14 days. All administrated ended 28 days. There was a statistically significant (P

In 2017 leptospirosis cases occur in new areas in Bantul where cases have never been previously reported. Cases still occur in 2018 with an interval of two months after the first case. Preventive and curative efforts in the context of controlling cases have been carried out by the local health office, in addition to these control efforts, it is also necessary to know the presence of Leptospira in rats and water bodies in the area as well as the history of patients transmission. This study was conducted to provide epidemiological data, especially the status of Leptospira in rats as reservoir animal and water bodies as well as a history of patient activity as basic data for leptospirosis control in Gilangharjo Village. This cross-sectional study was conducted at the case location in RT 03 Jodog, Gilangharjo Village, Pandak District, Bantul Regency, which was conducted in April 2018. Leptospira infection status was carried out on rats and water bodies by molecular examination, while the history of transmission based on interviews with patients and the result of the examination of Leptospira status. Rat species caught were dominated by R.tanezumi, R. norvegicus and B. indica. Positive rat infected with Leptospira were found in B. indica while in water bodies Leptospira contamination was not found. Infected rat can be a source of transmission for humans and other animals. Most of the patient's activities were carried out in the fields and at home, all of the patients had wounds that were not treated, and had a history of contact with rats that might transmit Leptospira to humans.

Background/aim Hyperthyroidism is associated with results in increased glomerular filtration rate as well as increased renin-angio- tensin-aldosterone activation. The disturbance of Ca2+ homeostasis in the endoplasmic reticulum (ER) is associated with many diseases, including diabetic nephropathy and hyperthyroidism. Transient receptor potential canonical 1 (TRPC1) channel is the first cloned TRPC family protein. Although it is expressed in many places in the kidney, its function is uncertain. TRPC1 is involved in regulating Ca2+ homeostasis, and its upregulation increases ER Ca2+ level, activates the unfolded protein response, which leads to cellular damage in the kidney. This study investigated the role of TRPC1 in the kidneys of hyperthyroid rats in terms of ER stress markers that are gluco- se-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), (protein kinase R (PKR)-like endoplasmic reticulum kinase) (PERK), Inositol-requiring enzyme 1 (IRE1). Materials and methods Twenty male rats were assigned into control and hyperthyroid groups (n = 10). Hyperthyroidism was induced by adding 12 mg/L thyroxine into the drinking water of rats for 4 weeks. The serum-free T3 and T4 (fT3, fT4), TSH, blood urea nitrogen (BUN), and creatinine levels were measured. The histochemical analysis of kidney sections for morphological changes and also im- munohistochemical and western blot analysis of kidney sections were performed for GRP78, ATF6, PERK, IRE1, TRPC1 antibodies. Results TSH, BUN, and creatinine levels decreased while fT3 and fT4 levels increased in the hyperthyroid rat. The morphologic analy- sis resulted in the capillary basal membrane thickening in glomeruli and also western blot, and immunohistochemical results showed an increase in TRPC1, GRP78, and ATF6 in the hyperthyroid rat (p < 0.05). Conclusion In conclusion, in our study, we showed for the first time that the relationship between ER stress and TRPC1, and their increased expression caused renal damage in hyperthyroid rats.

Abdominal adhesion is one of the main and important post-surgical problems and, according to available literature, the probability of their occurrence after surgery is higher than 50%. The present study intended to estimate the effect of Nano n-acetylcysteine on macroscopic and microscopic features post-surgical adhesions in an animal model. Twenty-five adult male Wistar rats, 200-220 gr, were randomly divided into five equal groups and underwent intramuscular anesthesia by injection of ketamine 10% at 50 mg/kg and injection of xylazine 2% at 5 mg/ kg. The treatments included three Nano-NAC groups at different dosages 50, 75 and 150 mg/kg, an NAC group, and a control group. On days 14 and 28 post-surgery, the abdomens of all rats were re-opened for macroscopic and microscopic evaluation of adhesions. Based on the results of macroscopic evaluation, the group receiving Nano-NAC 50 mg/kg had the lowest and the control group the highest mean adhesion scores on days14 and 28 post-operations. Histopathological evaluation also revealed that the group treated with Nano-NAC 50 mg/kg had the lowest level of inflammation and fibrosis score among the five groups on days 14 and 28 post-operation. Considering the results obtained in our experimental model and the increasing use of nanotechnology in the manufacture of biomedical drugs, it seems that use of Nano-NAC at low doses 50 and 75mg/kg after laparotomy can significantly reduce adhesions.

Objectives Several studies show that severe social stressors, e.g., in the form of exposure to workplace bullying in humans, is associated with negative mental health effects such as depression and anxiety among those targeted. However, the understanding of the underlying biological mechanisms that may explain the relationship between exposure to bullying and such negative health outcomes is scarce. The analyses presented here focus on understanding the role of the β2-adrenergic receptors (ADRB2) on this association. Methods First, a resident-intruder paradigm was used to investigate changes in circulating norepinephrine (NE) in rat serum induced by repeated social defeat and its relationship with subsequent social behavior. Second, the direct effects of the stress-hormones NE and cortisol, i.e., synthetic dexamethasone (DEX), on the ADRB2 expression (qPCR) and monocyte chemoattractant protein-1 (MCP-1) release (immunoassay) was examined in cultured EL-1 cells. Third, in a probability sample of 1052 Norwegian employees, the 9-item short version of the Negative Acts Questionnaire—Revised (S-NAQ) inventory, Hopkins Symptom Checklist and genotyping (SNP TaqMan assay) were used to examine the association between social stress in the form of workplace bullying and anxiety moderated by the ADRB2 genotype (rs1042714) in humans. Results The present study showed a clear association between reduced social interaction and increased level of circulating NE in rats previously exposed to repeated social defeat. Parallel cell culture work, which was performed to examine the direct effects of NE and DEX on ADRB2, demonstrated ADRB2 downregulation and MCP-1 upregulation in cultured EL-1 cells. Genotyping with regard to the ADRB2 genotype; rs1042714 CC vs CG/GG, on human saliva samples, showed that individuals with CC reported more anxiety following exposure to bullying behaviors as compared to the G carriers. Conclusion We conclude that workplace bullying promotes anxiety and threaten well-being through an ADRB2 associated mechanism.

OBJECTIVES Chronic liver disease increases the risk for periodontal disease and osteoporotic fractures, but its impacts on bone regeneration remain unknown. Herein, we studied the impact of liver cirrhosis on peri-implant bone formation. MATERIAL AND METHODS A total of 20 male Wistar rats were randomly divided into two groups: one with the common bile duct ligated (BDL) and the respective sham-treated control group (SHAM). After four weeks of disease induction, titanium mini-screws were inserted into the tibia. Successful induction of liver cirrhosis was confirmed by the presence of clinical symptoms. Another four weeks later, peri-implant bone volume per tissue volume (BV/TV) and bone-to-implant contact (BIC) were determined by histomorphometric analysis. RESULTS Peri-implant bone formation was not significantly different between the SHAM and BDL groups. In the cortical compartment, the median percentage of peri-implant new bone was 10.1% (95% CI of mean 4.0-35.7) and 22.5% (13.8-30.6) in the SHAM and BDL groups, respectively (p��=��.26). Consistently, the new bone in direct contact with the implant was 18.1% (0.4-37.8) and 23.3% (9.2-32.8) in SHAM and BDL groups, respectively (p��=��.38). When measuring the medullary compartment, the new bone area was 7.1% (4.8-10.4) and 10.4% (7.2-13.5) in the SHAM and BDL groups, respectively (p��=��.17). Medullary new bone in direct contact with the implant was 10.0% (1.2-50.4) and 20.6% (16.8-35.3) in SHAM and BDL groups, respectively, and thus comparable between the two groups (p��=��.46). CONCLUSIONS Bile duct ligation has no significant impact on the early stages of peri-implant bone formation.

The present study was performed to investigate the effect of maternal hypothyroidism and puberty onset in female rat pups. To do this, we employed propylthiouracil (PTU) to prepare a hypothyroid rat model. Pregnant rats were treated with PTU (0.025%) in drinking water from gestational day 14 to postnatal day 21 of offspring. Comparison of general indices such as body and tissue weights and puberty indices such as vaginal opening (VO) and tissue histology between control and PTU-treated rats were conducted. There was no significant difference in the date of VO between control and PTU group. The body weights of the PTU group were significantly lower, only 36.8% of the control group (p

Introduction There is a balance between oxidative stress, antioxidant capacity and immune response. Their roles in physiological and behavioural mechanisms are important for the maintenance of the organism’s internal equilibrium. This study aimed to evaluate the antioxidant effects of the exogenous alga Spirulina platensis (Arthrospira platensis) in a stress-induced rat model, and to describe its possible mechanism of action. Material and Methods Thirty-six adult male Sprague Dawley rats were separated into four groups: control (C), stress (S), S. platensis (Sp), and S. platensis + stress (SpS). The rats in groups Sp and SpS were fed with 1,500 mg/kg b.w./day Spirulina platensis for 28 days. All rats were exposed to prolonged light phase conditions (18 h light : 6 h dark) for 14 days. The SpS and S groups were exposed to stress by being kept isolated and in a crowded environment. Blood samples were obtained by puncturing the heart on the 28th day. The effect of stress on serum corticosterone, oxidative stress markers (TOS, TAC, PON1, OSI) and immunological parameters (IL-2, IL-4, IFN-ɣ) were tested. Also, the brain, heart, intestines (duodenum, ileum, and colon), kidney, liver, spleen, and stomach of the rats were weighed. Results Serum corticosterone levels were higher in the S group than in the C group, and significantly lower in the SpS group than in the S group. Mean total antioxidant capacity were lower in the S group than in the C group, and Spirulina reversed this change. Although not significantly different, IL-2 was lower in the S group than in the C group. However, in the SpS group, IL-2 increased due to Spirulina platensis mitigating effects of stress. Conclusion Male rats fed a diet with Spirulina platensis could experience significantly milder physiological changes during stress, although stress patterns may be different. Exogenous antioxidant supplements merit further investigation in animals and humans where the endogenous defence mechanism against stress may not be sufficient.

We aimed to investigate detrusor function in a previously developed rat neurogenic voiding dysfunction model that we have developed previously. We performed sham or bilateral accessory nerve injury (BACNI) surgeries on ten-week-old male Wistar/ST rats. One week after surgery, we evaluated detrusor contractility in the bladder using isometric tension and mRNA expression assays. Cholinergic contraction was attenuated in the injury model, whereas carbachol-evoked contraction was enhanced, and mRNA expression of the cholinergic receptor increased. These findings suggest that there was a reduction in neurotransmitter release causing detrusor underactivity.

Summary Compounds of natural origin are often used for their beneficial effects on the male endocrine system and the synthesis of steroid biomolecules in testicular tissue. One of such compounds is quercetin (QUE), which belongs to the flavonoid family and is found in a wide range of vegetables, fruits and plant products. The purpose of this study is to evaluate the impact of QUE on the endocrine function of rat testicular fragments under in vitro conditions. Testicular fragments from adult Wistar rats (n=9), cultured in the D-MEM medium with different concentrations of QUE (namely 1, 10 and 100 µmol/L) for 24 h at 37°C (5% CO2), were used in the experiment conducted. Following culture, the medium was separated and the levels of cholesterol (CHOL) and male hormones were measured. CHOL values were quantified spectrophotometrically, whereas the concentrations of androstenedione (ANDRO), dehydropeiandrosterone (DHEA) and testosterone (TEST) were quantified using the enzyme-linked immunosorbent assay (ELISA) commercial kit. The results obtained indicate that 10 µmol/L QUE significantly increased (P

Objectives: We aimed to investigate the radiological, biomechanical, histopathological, histomorphometric, and immunohistochemical effects of different doses of vardenafil on fracture healing. Materials and methods: Fifty-one rats were divided into three groups. Group V5 was given 5 mg/kg/day of vardenafil; Group V10 was given 10 mg/kg/day of vardenafil; and the control group was given the same volume of saline. Six rats from each group were sacrificed on Day 14 (early period) and the remaining rats were sacrificed on Day 42 (late period). Callus/femoral volume and bone mineral density were measured using micro- computed tomography. Five femurs from each group in the late period were examined by biomechanical tests. In addition to the histopathological and histomorphometric evaluations, immunohistochemical analyses were performed to examine the levels of inducible nitric oxide synthase (iNOS), transforming growth factor-3 (TGF-β3), and nuclear factor kappa B (NF-κB) proteins. Results: Both doses of vardenafil increased primary bone volume and maximal bone fracture strength in late period, compared to the control group (p^lt;0.05). Histological healing scores of vardenafil groups were significantly higher in early period (p Conclusion: During the first period of fracture healing process in which vasodilation is mostly required with increasing inflammation, vardenafil has ameliorating effects on the bone union and supports fracture healing.

Methionine (MET) rich diets, smoking, coffee and alcohol consumption, low physical activity, and aging are related to high plasma concentrations of homocysteine, which can jeopardize the heart health. Although hyperhomocysteinemia has been considered a recognized risk factor for cardiac dysrhythmia, the structural changes of the conductive system, including Sinoatrial (SA) node of the heart involved in the disorder, have not been completely clarified. Curcumin is the main component of turmeric and has shown some cardioprotective effects. This study aimed to evaluate the effect of curcumin on the structural changes of the SA node in L-MET-treated rats. These alterations were evaluated by means of stereological techniques, namely cavalieri principle for volume estimation and optical disector counting technique for cell counting. Both techniques used two-dimensional images for obtaining three-dimensional parameters. The rats were divided into four groups, including control, MET-treated (1 g/kg/day), curcumin-treated, (100 mg/kg/day), and MET + curcumin. The treatments were performed for 28 days. On the final day, SA nodes were dissected out for stereological investigation. Compared to the control rats, the volume of SA node, total volume of grape-like cell clusters, and number of SA node cells were respectively decreased by 42%, 34%, and 37% in the MET-treated group (p

Bu çalışma, deneysel olarak kronik florozis oluşturulan ratlarda vitamin C (vit C) ve E (vit E)'nin serum protein fraksiyonları üzerindeki etkilerini araştırmak amacıyla planlandı. Materyal olarak Wistar-Albino ratlar kullanıldı (Her biri 8 rat içeren, 8 grup). Deneme grupları; kontrol grubu, deneysel florozis grubu, koruma grupları (16 hafta boyunca, içme suyu içeren günlük 150 ppm NaF içeren içme suyu/ad-libitum ile birlikte vit C (100 mg / kg), vit E (300 mg / kg) ve vit C + vit E (100 mg/kg + 300 mg/kg)) ve tedavi grupları (16 hafta boyunca 150 ppm NaF içeren içme suyu/ad-libitum verildikten sonra tedavi amacıyla 4 hafta vit C (100 mg/kg), vit E (300 mg / kg) ve vit C + vit E (100 mg/kg + 300 mg/kg)) olarak oluşturuldu. Deneme sonunda kan örnekleri toplandı ve serumlar alındı. Bu örneklerde serum protein fraksiyonları selüloz-asetat elektroforezi ile belirlendi. Deneysel florozis grubunda total protein yüzde gram açısından, alfa-1’in önemli oranda azaldığı ve beta globülinlerin arttığı tespit edildi. Korunma ve tedavi amacıyla vitamin C, vitamin E ve vitamin C+vitamin E birlikte verildiği gruplarda, değişen bu değerlerin kontrol grubuna yaklaştığı görüldü. The aim of the present study was to investigate the effects of vitamins C (vit C) and E (vit E) on the serum protein fractions in rats with experimentally-induced chronic fluorosis. Wistar-Albino rats (male) were used as material (8 groups, each containing 8 rats). The experimental groups were control, protection groups (daily 150 ppm NaF containing drinking water for 16 weeks as ad-libitum, and, on alternate Vit C (100 mg/kg), Vit E (300 mg/kg) and Vit C+ Vit E (100 mg/kg + 300 mg/kg) for 16 weeks) therapy groups (daily 150 ppm NaF containing drinking water for 16 weeks as ad-libitum, then normal drinking water as ad-libitum, Vit C (100 mg/kg), Vit E (300 mg/kg) and Vit C + Vit E (100 mg/kg + 300 mg/kg) on alternate for 4 weeks). The end of experimental period, blood samples were collected and serums were obtained. Serum protein fractions in blood samples were determined with cellulose-acetate electrophoresis. Alpha-1 was significantly decreased and beta globulins increased in the experimental fluorosis group. In the groups in which vitamin C, vitamin E and combine combination of vitamin C and vitamin E were given for prevention and treatment, it was observed that these changing values approach to the control group.

Bile acids (BAs) are signalling molecules that mediate various cellular responses in both physiological and pathological processes. Several studies report that BAs can be detected in the brain1, yet their physiological role in the central nervous system is still largely unknown. Here we show that postprandial BAs can reach the brain and activate a negative-feedback loop controlling satiety in response to physiological feeding via TGR5, a G-protein-coupled receptor activated by multiple conjugated and unconjugated BAs2 and an established regulator of peripheral metabolism3–8. Notably, peripheral or central administration of a BA mix or a TGR5-specific BA mimetic (INT-777) exerted an anorexigenic effect in wild-type mice, while whole-body, neuron-specific or agouti-related peptide neuronal TGR5 deletion caused a significant increase in food intake. Accordingly, orexigenic peptide expression and secretion were reduced after short-term TGR5 activation. In vitro studies demonstrated that activation of the Rho–ROCK–actin-remodelling pathway decreases orexigenic agouti-related peptide/neuropeptide Y (AgRP/NPY) release in a TGR5-dependent manner. Taken together, these data identify a signalling cascade by which BAs exert acute effects at the transition between fasting and feeding and prime the switch towards satiety, unveiling a previously unrecognized role of physiological feedback mediated by BAs in the central nervous system. Bile acids are shown to enter the brain and regulate short-term reductions in food intake after a meal by inhibiting neuropeptide release from agouti-related peptide/neuropeptide Y neurons.

Background and purpose: The specific molecular mediators involved in dyslipidemia in older people are not yet clearly understood. The current study was, thus, an attempt to investigate whether moderate aerobic exercises and curcumin administration alleviates the abnormalities caused by aging in the rats' liver. Experimental approach: Thirty-two eight-year-old young rats were classified into five groups, namely, young control, aged control, aged-curcumin, aged-exercise, and aged-curcumin-exercise co-treatment. The rats in the exercise groups were trained on an animal treadmill for 60 min/day five times per week for eight weeks. Findings/Results: The results revealed a significant increase in FAT/CD36, PTP1B, significantly decreased HNF4α genes expression, increase in LDL and cholesterol in the aged group compared to the young control. Compared to those in the young control group, no significant changes in HDL and TG amounts in the aged control were observed. Moreover, compared to the young control, the aged group showed liver histological changes such as fibrosis and mild or grade 1 steatohepatitis. Moderate aerobic exercise and curcumin alone or in combination completely masked this effect. Conclusion and implications: The findings revealed dyslipidemia and liver steatosis related to aging might be partly associated with changes in hepatic transcriptional factors which can be mitigated via moderate aerobic exercise and curcumin.

Diabetes mellitus (DM) has emerged as a public healthcare problem. Sustained hyperglycemia has been linked with many complications including impaired male fertility. The aim of the study: to evaluate the effect of STZ-induced diabetes mellitus on testicular immunomorphology both in the peripubertal period and adulthood of rats. Material and methods. Peripubertal male rats were injected with STZ (70 mg/kg), adult rats received 60 mg/kg. Immunohistochemical staining was performed to assess cell proliferation (Ki-67), apoptosis (caspase-3), expression of androgen receptors (AR), Wilms Tumor (WT1) protein. Also, the morphology of blood vessels was analyzed on the basis of CD34-immunoreactivity. Taking into consideration the small groups of animals, statistical analysis was made with the Mann–Whitney U test. Results. Fewer rows of proliferating spermatogonia were observed in the experimental animals (P < 0.05) of both age groups. Surprisingly, diabetes resulted in decreased caspase-3 expression (P < 0.05) except for the early period (2 weeks) in the peripubertal group, in which this trend was not observed. The same principles are true in terms of AR expression in seminiferous tubules. Hyperglycemia prevented immature testes from the complete development but thickens the walls of microvessels (P < 0.05). Also, the atrophy of spermatogenic epithelium and Sertoli cells was registered in most tubules of all the experimental groups (P < 0.05). Conclusion. the diabetic injury of testicular tissue is a long time process possessing characteristic feature in the peripubertal period, for example, the later development of AR deficiency. In addition, the high level of apoptosis is characteristic of an immature testis and so is the tendency of caspase-immunoreactivity to persist. Цукровий діабет (ЦД) – суттєва проблема системи охорони здоров’я. Тривала гіперглікемія пов’язана з багатьма ускладненнями, включаючи порушення фертильності чоловіків. Мета роботи – оцінити вплив індукованого стрептозотоцином (STZ) цукрового діабету на імуноморфологію яєчок щурів у перипубертатному періоді та дорослому віці. Матеріали та методи. Перипубертатним самцям щурів уводили STZ у дозі 70 мг/кг, дорослі щури отримували 60 мг/кг. Імуногістохімічні реакції проводили для оцінювання проліферації клітин (Ki-67), апоптозу (caspase-3), експресії рецепторів андрогенів (AR), білка пухлини Вільмса (WT1). Також аналізували морфологію судин на основі CD34-імунореактивності. Враховуючи невеликі групи тварин, статистичний аналіз здійснили за допомогою тесту Манна–Вітні. Результати. В експериментальних тварин (р < 0,05) обох вікових груп спостерігали менше рядків сперматогоній, що мітотично діляться. Дивно, але діабет призвів до зниження експресії каспази-3 (р < 0,05), за винятком раннього періоду (2 тижні) у групі перипубертату, в якій цей тренд не зафіксований. Подібні закономірності виявлені для експресії рецепторів андрогенів. Гіперглікемія запобігла повноцінному розвитку незрілих яєчок, але потовщила стінки мікросудин (p < 0,05). Також зареєстровано атрофію сперматогенного епітелію та клітин Сертолі в більшості канальців у всіх експериментальних групах. Висновки. Діабетичне пошкодження тканин яєчок – тривалий процес, що має характерні особливості в перипубертатному періоді, наприклад пізніший дефіцит AR. Крім того, високий рівень апоптозу характерний для незрілого яєчка, як і тенденція до збереження caspase3-імунореактивності. Сахарный диабет (СД) стал значительной проблемой здравоохранения. Длительная гипергликемия связана со многими осложнениями, включая нарушения фертильности мужчин. Цель работы – оценить влияние индуцированного стрептозотоцином (STZ) сахарного диабета на иммуноморфологию яичек крыс в перипубертатном периоде и взрослом возрасте. Материалы и методы. Перипубертатным самцам крыс вводили STZ в дозе 70 мг/кг, взрослые крысы получали 60 мг/кг. Иммуногистохимические реакции проводили для оценки пролиферации клеток (Ki-67), апоптоза (caspase-3), экспрессии рецепторов андрогенов (AR), белка опухоли Вильмса (WT1). Также анализировали морфологию сосудов на основе CD34-иммунореактивности. Учитывая небольшие группы животных, статистический анализ провели с помощью теста Манна–Уитни. Результаты. У экспериментальных животных обеих возрастных групп отмечено меньше рядов митотически делящихся сперматогоний (р < 0,05). Удивительно, но диабет привел к снижению экспрессии каспазы-3 (р < 0,05) за исключением раннего периода (2 недели) в группе перипубертата, в которой этот тренд не зафиксирован. Подобные закономерности обнаружены для экспрессии рецепторов андрогенов. Гипергликемия предотвратила полноценное развитие незрелых яичек, но стенки микрососудов стали толще (p < 0,05). Также зарегистрировали атрофию сперматогенного эпителия и клеток Сертоли в большинстве канальцев во всех экспериментальных группах. Выводы. Диабетическое повреждение тканей яичек – длительный процесс, имеющий характерные особенности в перипубертатном периоде, например дефицит AR развивается впоследствии. Кроме того, высокий уровень апоптоза характерен для незрелого яичка, как и тенденция к сохранению caspase3-иммунореактивности.

In this study, it was aimed to investigate the protective effect of Resveratrol, which has a strong antioxidant effect on kidney tissues of rats experimentally induced with carbon tetrachloride with nephrotoxicity, by kidney function tests and histopathology. For this purpose, 32 male Wistar Albino rats were used. The subjects were randomly selected, 1stgroup control, 2ndgroup CCl4, 3rdgroup Resveratrol. The 4thgroup was divided into 4 groups as CCl4 + Resveratrol. At the end of the experiment, animals were sacrificed under anesthesia and kidney samples were taken in 10% formalin solution for histopathological analysis. In the histopathological examination, it was found that the rats in the control and Resveratrol groups had normal kidney histological structure. In CCI4group, severe hydropic degeneration in tubules epithelium, mild coagulation necrosis in tubules epithelium and severe hyperemia in the vessels were observed. When kidney tissues of rats were examined in CCI4+ Resveratrol group, mild hydropic degeneration in tubules epithelium and mild hyperemia in vessels were observed. When the kidney tissues of the rats in the Resveratrol group were examined, it was observed that they had a normal histological appearance. As a result, it was determined that Resveratrol has a protective effect on kidney damage caused by CCI4.

Ivasivka K. P., Paltov E. V., Masna Z. Z. Characteristics of changes in the structural components of the mucosa and rat laryngeal cartilage at the end of the third week of experimental opioid exposure. Journal of Education, Health and Sport. 2021;11(04): 58-71. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2021.11.04.007 https://apcz.umk.pl/czasopisma/index.php/JEHS/article/view/JEHS.2021.11.04.007 https://zenodo.org/record/4723875 The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019. © The Authors 2021; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 26.02.2021. Revised: 31.03.2021. Accepted: 27.04.2021. UDK:616.321 – 018.3+616.321- 018.73):615.212.7]-092.9 Characteristics of changes in the structural components of the mucosa and rat laryngeal cartilage at the end of the third week of experimental opioid exposure K. P. Ivasivka, E. V. Paltov, Z. Z. Masna Danylo Halytsky Lviv National Medical University, Lviv, Ukraina Department of Normal Anatomy Ivasivka K. P. https://orcid.org/0000-0003-4372-225X Paltov E. V. https://orcid.org/0000-0002-2622-4753 Masna Z. Z. https://orcid.org/0000-0003-20577061 Abstract In our work we aimed to study the pathomorphological manifestations among the structural components of the laryngeal mucosa and cartilage in the early stages of the experimental opioid effect. This goal was achieved through the use of histological techniques to visualize the structural components of the laryngeal mucosa and cartilage. Histological sections with a thickness of 5 - 7 mm were made. Histological specimens were prepared according to conventional methods using the dye hematoxylin, eosin, azan according to the method of Heidenhain, PAS-reaction according to Mc-Manus and Alcian blue according to Steedman. Microscopic examinations and photographing of the preparations were performed using an MBI-1 microscope and a Nicon D 3100 digital camera. At the microstructural level after 21 days in rats there was an increase in dyscirculatory changes, which were most pronounced in the vessels of the lamina propria of the laryngeal mucosa. The epithelial layer of the epiglottis was inhomogeneously thickened, especially on the pharyngeal surface. Small polymorphonuclear infiltrates were found in the laryngeal mucosa of the epiglottis. The vessels of the laryngeal ventricular mucosa of the larynx were dilated and filled with erythrocytes. The development of perivascular edema was registered. In the areas of transudate accumulation, the main substance of the laryngeal mucosa of the larynx was enlightened. Necrotic changes developed in the epitheliocytes of the laryngeal ventricle. Eosinophilic mass accumulated on the surface of the ventricular mucosa. The results of the study in the future will form a pathomorphological base that can be used for comparative characterization of the dynamics of growth of pathomorphological changes in the structural components of the laryngeal mucosa and cartilage in the early stages and compare these changes with pathomorphological manifestations in the late stages of experimental opioid exposure. Key words: opioid; laryngeal mucosa; laryngeal cartilage; rat; early terms.

Background Many non-union animal models have been developed to explore the problems surrounding fracture healing. However, the existing models are not perfect and cannot satisfy all non-union studies. This study aimed to make a non-union model of the tibia in rats by cauterization of the posterior of 2 mm on both sides of the fracture end after open osteotomy of the tibia and fixing the fractured tibia with a Kirschner wire 0.8 mm in diameter. Methods For this study, 96 female adult Sprague-Dawley (SD) rats were used. The rats underwent surgery to produce a tibial open fracture and were fixed with a 0.8-mm diameter Kirschner wire. In 48 of the rats, the periosteum proximal and distal to the fracture end was cauterized. Results At 2, 4, 6, and 8 weeks after surgery, radiological and histological analysis showed typical physiological healing in the control group, and the healing rate was 100% at 6 weeks. But the non-union group was characterized by resorption of the fracture ends with few callus formations and no bridging callus formation, and the healing rate was 0% at 8 weeks. Conclusions This method represents a reproducible model to create atrophic non-unions. This model provides a new option for studying the basic healing mechanisms and evaluating new therapies for bone regeneration and treatment of non-unions.

Summary: Background: Clinically, osteoarthritis manifests as joint pain with concomitant loss of joint function, which may ultimately result in a substantially reduced quality of life for the patient. Although, a lot is known about the symptom of the disease, the pathophysiology behind the structural changes is complex and poorly understood. By understanding the mechanisms driving joint tissue destruction in osteoarthritis and identifying the key factors involved, new targets for therapy are emerging that will go beyond symptomatic relief to slowing or stopping the progression of osteoarthritis. Aim: Thus, the aim of this study was to evaluate the effect of honey on disease progression, pain perception and inflammation in monosodium iodoacetate (MIA)-induced knee osteoarthritis in female Wistar rats. Methods: Thirty, twelve-month old female Wistar rats, weighing between 200 g & 250 g, were randomly divided into five groups of six animals each. Animals in group one were not induced and served as the control, while animals in groups two to five were injected with monosodium iodoacetate in the right knee. In addition, animals in group two received normal saline (1 ml/kg b.w.), group three received arthocare (glucosamine/chondroitin sulphate 6.67/8.33 mg/kg b.w.), group four received low dose honey (250 mg/kg b.w.) while group five received high dose honey (1,000 mg/kg b.w.) and were treated for twenty one days. All animals were subjected to assessment of tactile allodynia (von Frey test), acute inflammation (knee edema), and serum biomarkers: tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), prostaglandin E2 (PG E2) & cartilage oligomeric matrix protein (COMP) as well as histo-pathological assessment of the right knee joint. Results: Honey (at high and low doses), significantly (p

Neither HFD nor NES-1 changed methylcellulose emptying, but NES-1 delayed saline emptying in cannulated ND-rats. Inhibitory effect of NES-1 on gastric emptying in ND-rats was reversed by all antagonists, and abolished in HFD-rats. In HFD-rats, carbachol-induced contractility was enhanced in gastric, but inhibited in ileal strips. HFD increased body weight, while serum triglycerides, alanine transaminase, aspartate aminotransferase, glucose, and levels of malondialdehyde, glutathione, myeloperoxidase activity, and luminolchemiluminescence in hepatic, ileal, and adipose tissues were similar in ND- and HFD-rats, but only lucigenin-chemiluminescence was Background/Aims Gastrointestinal motility changes contribute to development and maintenance of obesity. Nesfatin-1 (NES-1) is involved in central appetite control. The aim is to elucidate effects of NES-1 and high-fat diet (HFD) on gastrointestinal motility and to explore myenteric neuron expressions of tyrosine hydroxylase (TH), vasoactive intestinal peptide (VIP), and neuronal nitric oxide synthase (nNOS) in HFDinduced oxidative injury. Methods Sprague-Dawley rats were fed with normal diet (ND) or HFD. Gastric emptying rate was measured following NES-1 (5 pmol/rat, intracerebroventricular) preceded by subcutaneous injections of glucagon-like peptide 1 (GLP-1), cholecystokinin 1 (CCK-1), and gastrin/CCK-2 receptor antagonists. In carbachol-contracted gastric and ileal strips, contractile changes were recorded by adding NES1 (0.3 nmol/L), GLP-1, CCK-1, and gastrin/CCK-2 antagonists. Results Neither HFD nor NES-1 changed methylcellulose emptying, but NES-1 delayed saline emptying in cannulated ND-rats. Inhibitory effect of NES-1 on gastric emptying in ND-rats was reversed by all antagonists, and abolished in HFD-rats. In HFD-rats, carbachol-induced contractility was enhanced in gastric, but inhibited in ileal strips. HFD increased body weight, while serum triglycerides, alanine transaminase, aspartate aminotransferase, glucose, and levels of malondialdehyde, glutathione, myeloperoxidase activity, and luminolchemiluminescence in hepatic, ileal, and adipose tissues were similar in ND-and HFD-rats, but only lucigenin-chemiluminescence was increased in HFD-rats. Vasoactive intestinal peptide (VIP) and TH immunoreactivities were depressed and nNOS immunoreactivity was increased in gastric tissues of HFD-rats, while VIP and TH were enhanced, but nNOS was reduced in their intestines. Conclusions HFD caused mild systemic inflammation, disrupted enteric innervation, enhanced gastric contractility, inhibited ileal contractility, and eliminated inhibitory effect of NES-1 on gastric motility. (J Neurogastroenterol Motil 2021;27:265-278)

In this study, the effects of grape seed extract on insulin, adiponectin and resistin levels in diabetic rats were aimed to investigate. Weight of about 300-350g 7-8 weeks 32 female Wistar Albino rats were used. Weight of about 300-350g 7-8 weeks 32 female Wistar Albino rats randomly divided into four groups of eight each: control group (C), group with diabetes (DM), grape seed extract group (GSE), diabetes mellitus and grape seed extract group (DM+GSE). The diabetic group 45 mg/kg single dose of streptozotocin was administered intraperitoneally, and the grape seed extract groups (DM+GSE and GSE) grape seed extract was given orally every day with an intragastric tube for 20 days (0.6 ml/rat). Blood samples were taken from the hearts of rat‘s end of the experiment. The sera obtained were used for insulin, adiponectin and resistin analysis measured via ELISA with commercial kits. The insulin and adiponectin levels of the rats in the diabetes + grape seed extract group were found to be higher than those in the diabetes group. There was no significant change in the resistin level differences between the groups. As a result; It is possible to say that grape seed extract has an increasing effect on insulin level and adiponectin levels of diabetic rats are decreased due to diabetes and it has no significant effect on resistin levels. Detected by the positive effects of grape seed extracts, it may be useful to use for the regulating of the diabetes in human.

The heat shock protein (Hsp70) level was assessed after 14 days of oral gavage-exposure to fumonisin B1 (FB1: 150 µg/animal/day), deoxynivalenol (DON: 30 µg/animal/day) and zearalenone (ZEN: 150 µg/animal/day), alone or in combinations (in additive manner: FD = FB1 + DON, FZ = FB1 + ZEN, DZ = DON + ZEN and FDZ = FB1 + DON + ZEN) in the liver, kidneys and lung of 24 adult male Wistar rats (n = 3/group). The liver was the most responsive tissue, as compared with kidney and lung. Except of DZ-treatment, mycotoxins elevated the Hsp70 levels in livers. The highest Hsp70-levels (≈ twofold) were in the DON, FD, FZ and FDZ treatments (additive effects). In the kidney, alterations (↑ ≈ twofold) were detected in ZEN, FD, FZ and DZ treatments. The least responsive organ was the lung (↑ only in FDZ, antagonistic effect). DON and ZEA exposures have altered the reduced glutathione concentration (↓) and glutathione peroxidase activity (↓) in the blood serum. The serum malondialdehyde level increased only after exposure to FD (synergistic effect), as compared with the DZ group (antagonistic effect). When the blood clinical chemistry was assessed, significant alterations were in alanine aminotransferase (80% increase in FDZ, antagonistic effect) and total protein (↓ ZEN). Results varied according to the organ, toxin type and interactions. Furthermore, oxidative stress was not the only key player behind the Hsp70 increase, in which another mechanism is suggested.

Highlights • Injuries with embedded metal fragments are an increasing medical concern. • Metal pellets implanted in the leg muscles of rats solubilize and release metal. • The solubilized metals pass through the kidney and are excreted in the urine. • Several urinary biomarkers of renal health are affected by the excreted metals., Background Wounds with embedded metal fragments are an unfortunate consequence of armed conflicts. In many cases the exact identity of the metal(s) and their long-term health effects, especially on the kidney, are not known. Aim of study The aim of this study was to quantitate the urinary levels of metals solubilized from surgically implanted metal pellets and to assess the effect of these metals on the kidney using a battery of biomarker assays. Materials and methods Using a rodent model system developed in our Institute to simulate embedded fragment injuries, eight metals considered likely components of an embedded fragment wound were individually implanted into the gastrocnemius muscle of male Sprague-Dawley rats. The rats were followed for 12 months post-implantation with urine collected prior to surgery then at 1-, 3-, 6-, 9-, and 12-months post-implantation to provide a within-subjects cohort for examination. Urinary metal levels were determined using inductively coupled plasma-mass spectrometry and urinary biomarkers assessed using commercially available kits to determine metal-induced kidney effects. Results With few exceptions, most of the implanted metals rapidly solubilized and were found in the urine at significantly higher levels than in control animals as early as 1-month post-implantation. Surprisingly, many of the biomarkers measured were decreased compared to control at 1-month post-implantation before returning to normal at the later time points. However, two metals, iron and depleted uranium, showed increased levels of several markers at later time points, yet these levels also returned to normal as time progressed. Conclusion This study showed that metal pellets surgically implanted into the leg muscle of Sprague-Dawley rats rapidly solubilized with significant levels of the implanted metal found in the urine. Although kidney biomarker results were inconsistent, the changes observed along with the relatively low amounts of metal implanted, suggest that metal-induced renal effects need to be considered when caring for individuals with embedded metal fragment wounds.

Aims Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a new class of antidiabetic drugs, are nephroprotective in case of diabetes, but whether a similar beneficial effect may be detectable also in case of chronic non-diabetic kidney diseases remains still unknown. The aim of this study was to evaluate the effects of empagliflozin, a SGLT-2 inhibitor, on the progression of cyclosporine nephropathy, in the absence of diabetes. Methods Sprague Dawley rats (n = 27) have been fed with low-salt diet starting 10 days before the beginning and finished at the end of the experimental period. Cyclosporine-A (CsA, 15 mg/kg/day, intraperitoneal injection, n = 8) and CsA plus empagliflozin (Empa, 10 mg/kg/day, per os, n = 7) were administered for 4 weeks. The control groups were treated with placebo (Control, n = 7) or empagliflozin (Control + Empa, n = 5). Blood pressure (plethysmographic method) was measured at the beginning and at the end of the experimental period. At the end of the experimental protocol, the kidneys were excised for histomorphometric analysis of renal fibrosis and for immunohistochemical evaluation of inflammatory infiltrates (monocytes/macrophages), type I and type IV collagen expression, and tyrosine hydroxylase expression, used as marker of sympathetic nerve activity. Results CsA-treated rats showed a significant increase (p p p p p p p p p p p Conclusion Empagliflozin administration caused a reduction in blood pressure in CsA-treated rats and showed a protective effect on CsA nephropathy by decreasing renal fibrosis, type I and type IV collagen expression, macrophage infiltration and tyrosine hydroxylase expression. These data suggest that empagliflozin promotes nephroprotection also in non-diabetic kidney disease.

Ethanol is the active ingredient in alcoholic beverages. As ethanol consumption increases from zero to very high, it is still unknown which metabolites are present at different times and which are essential to normal functioning. In this article, we used an intermittent-access 20% ethanol drinking paradigm to make Wistar male rats voluntarily drink large amounts of ethanol for 10, 20, 30, and 50 days, respectively. A hydrogen-1 nuclear magnetic resonance approach was used to investigate the time-dependent neurochemical metabolites spectra in the hippocampus, striatum, nucleus accumbens and prefrontal cortex. Multivariate pattern recognition techniques were used to analyze the hydrogen-1 nuclear magnetic resonance spectra data. Metabolic profiling was obtained, differentiating the ethanol-treated and control rats. The ethanol-affected metabolites disrupted processes associated with neurotransmitters, oxidative stress, energy metabolism and amino acids. Together, our findings demonstrate broad, dynamic, and time-dependent endogenous metabolic alterations in rats treated with ethanol.

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women. Objective: The aim of this study was to investigate the therapeutic effect of hydroalcoholic extract of Nigella sativa (N. sativa) seed as a plant, the consumption of which has been recommended in Islam, on dehydroepiandrosterone (DHEA)-induced PCOS rats. Materials and Methods: This experimental study was carried out on 36 Wistar female rats (3 wk, 60 ± 10 gr). Then rats were divided into 6 groups (n = 6/each): control; PCOSinduced (DHEA 60 mg/kg/sc); PCOS + Metformine (30 mg/kg); and three experimental groups receiving DHEA + hydroalcoholic extract of N. sativa seeds in doses of 50, 100 and 200 mg/kg, respectively. Blood samples were taken for the evaluation of sexual hormones, oxidative stress, glucose, and insulin after 30 days of treatment. Ovarian tissue was used for histopathological study. Results: The serum levels of luteinizing hormone, testosterone, glucose, insulin resistance, malondialdehyde, and insulin (p ≤ 0.001) and estrogen increased while the levels of progesterone (p = 0.01) and antioxidant enzymes in the PCOS group decreased (p ≤ 0.001). Conclusion: The administration of the N. sativa extract to the PCOS rats resulted in remarkable changes in the serumic factors relative to the PCOS group. In addition, the extract improved the structure of the ovarian tissue in the PCOS rat. The histopathological results which are in accordance with biochemical findings imply that N. sativa seed could be useful in the treatment of PCOS, the higher doses of the extract being more effective. Key words: Nigella sativa seed, Oxidative stress, Insulin resistance, Polycystic ovary syndrome, Rat.