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Introduction. Cognitive impairments are important components of the clinical picture of many neuropsychiatric disorders, and are in dire need of evidence-based pharmacotherapeutic approaches.The objective was to test a model of delayed cognitive impairments due to neonatal administration of NMDA receptor antagonists (7th, 9 th, and 11 th days of life).Methods and materials. Male Wistar rats were administered with phencyclidine, 10 mg/kg (Experiment 1), or (+)MK-801, 1 mg/kg (Experiment 2); then «2-choice serial reaction time task», or «reinforcement learning task based on response patterning under interval schedules of reinforcement» in the same adult rats were performed.Results. Experiment 1: rats after neonatal NMDA-blockade performed operant tasks more accurately and made fewer missed attempts as compared to control. Experiment 2: switching to another schedule of reinforcement increased the pause after reinforced responses in both groups; in the experimental group, the duration of the post-reinforcement pause was shorter.Conclusion. Neonatal NMDA receptor blockade affects inhibitory control and attention to sensory stimuli, which manifests, respectively, as increased impulsivity and hyperfocusing in limited-choice conditions.

Background and purpose: Wound is a complication that is highly prevalent. The aim of this study was to investigate the effect of a lipogel formulation containing Rhamnus cathartica L., a native Iranian plant, on wound healing in Wistar rats. Materials and methods: In this experimental study, to find the best lipogel formula, several formulations with different ratios of paraffin, polyethylene and extract were examined. Twenty rats were divided into four groups (n=5), including normal saline, lipogel base, extract lipogel, and active water. Full-thickness wound of 2*2 cm was induced in the ​​ dorsal area. Wound size evaluation and histopathological study were done at days 3, 5, 7, and 12. Results: The formulation containing 95% paraffin and 5% polyethylene was selected due to better skin coverage, good consistency, and better uniformity. Total phenolic content and total flavonoid content of R. cathartica were 4.5 mg/g and 23.415mg/g, respectively. In vivo results indicated significant differences in wound size between the treatment group and other groups (P≤0.05). Histopathology studies showed that the R. cathartica extract had a better effect on collagen deposition, necrosis, fibroblast maturation, and epidermis formation compared with other groups (P≤0.05). Conclusion: This study showed that lipogel containing the R. cathartica extract was effective in full-thickness wound healing.

ObjectiveTo establish a rat model of collagen-induced arthritis (CIA), a rat model of rheumatoid arthritis, and to study the protective effect of dexamethasone (DEX) on cartilage in CIA rats.MethodsThirty Wistar rats were randomly divided into three groups: normal, model, and DEX groups. The CIA model was established by intradermal injection of a white emulsion mixed with 0.1 mL bovine type II collagen and Freund's incomplete adjuvant in equal proportions into the distal part of the rat tail. The dates of the two injections were recorded as days 0 and 7, respectively. After the establishment of the CIA model, DEX (1 mg/kg) was intraperitoneally injected in the treatment group 3 times a week for 4 weeks. After the administration, the rats were euthanized, and the knee cartilages of 10 rats in each group were divided into three parts. The first part was fixed, decalcified, and stained with Alcian blue to observe the pathological changes in the cartilage layer. The second part was used for detection of mRNA expression of matrix metalloproteinase (MMP)-9 and MMP-13, and a disintegrin-like and metalloproteinase with thrombo-spondin motifs (ADAMTS)-4 and ADAMTS-5 by using real-time quantitative PCR analysis in the femoral head cartilage. The third part was used for detection of the expression levels of MMP-9, MMP-13, and ADAMTS-5 using immunohistochemistry in the cartilage layer of knee joint.ResultsCompared with the model group, the decrease of cartilage area, cartilage thickness, and cartilage cell numbers were significantly inhibited after DEX treatment (P

Introduction: Ficus capensis has been used in traditional medicine to treat anaemia, tuberculosis, convulsion, pains, wounds, respiratory disorders, and other health challenges. This study investigated the effect of F. capensis ethanolic leaf extract in phenylhydrazine (PHZ)-induced anaemia in Wistar rats. Methods: Induction of anaemia was done by intraperitoneal administration of PHZ (40 mg/kg for 48 hours). A normal group and an anaemic group were treated daily with a single dose of 20 mL/kg of distilled water and considered as control and anaemic (non-treated) groups. Then, the remaining groups were treated with 100, 200, and 400 mg/kg of ethanol extract of F. capensis leaves for 21 days, respectively. Blood samples from the rats were run in three batches of baseline, post anaemia induction, and post-treatment. Phytochemical screening and acute toxicity tests of the extract were also carried out following standard procedures. Results: The results showed a consistent significant increase in haematological parameters among various experimental groups. Haemoglobin (Hb), red blood cell (RBC) count, mean corpuscular volume (MCV), packed cell volume (PCV), mean cell haemoglobin (MCH) and Mean cell haemoglobin concentration (MCHC) values of treated rats were significantly increased compared to the anaemic control. The secondary metabolites of leaf extract were alkaloids, saponins, tannins, steroids, flavonoids, phenols, and reducing sugar, while the acute toxicity test was found to be non-toxic at 5000 mg/kg in rats. Conclusion: The ethanol leaf extract of F. capensis might provide an alternative cure for anaemia and boosts blood count.

Abstract Background Pyrazinamide (PZA) is efficient antituberculosis drug. However, PZA-induced hepatotoxicity mediated by oxidative damage is documented. Naringenin (NGN) is a common flavanone with antioxidative properties. Thus, the present work aimed to elucidate the protective role of NGN against PZA-induced toxicity in rats. Eighty adult male Wister rats were randomly divided into four groups: control, PZA, NGN and NGN+PZA. Rats were orally administered 155 mgPZA/kg or 50 mgNGN/kg or NGN 1 h before PZA daily. After 1, 2, 3 and 4 weeks, blood and liver were collected for hematological, biochemical, and histopathological investigations. Results Administering PZA alone caused remarkable declines in the white and red blood cell counts, hemoglobin content, packed cell volume, and serum levels of albumin, albumin/globulin ratio, high-density lipoprotein cholesterol, and hepatic activities of superoxide dismutase, and glutathione reductase and glutathione level. Serum levels of total cholesterol, low-density lipoprotein cholesterols, triglycerides, globulin, glucose, total and indirect bilirubin, malondialdehyde, and aminotransferases activities were markedly elevated. Additionally, the liver of PZA group exhibited considerable histopathological alterations. Inversely, in the NGN+PZA group, all the aforesaid disturbances in the studied parameters were ameliorated. Conclusions The current study revealed that NGN can be successfully utilized during treatment with PZA to prevent its side actions.

Context: Interruptins A and B derivatives from edible fern Cyclosorus terminans have been reported properties including anti-bacterial, anti-cancer, anti-oxidation, anti-inflammatory, and antidiabetic activities. Unfortunately, studies on its safety are still scarce. Aims: To evaluate the acute oral toxicity of interruptin-rich extract (IRE) from C. terminans in Wistar rats and examine the antidiabetic potential of IRE in vitro. Methods: IRE was evaluated cytotoxicity by MTT assay and potency of glucose consumption in hepatocyte and skeletal muscle cells. IRE was evaluated for acute toxicity in Wistar rats by following OECD 420 guidelines. Wistar rats were single oral administrated of 2000 mg/kg IRE and further observed for 14 days. LCMS was assessed for verifying IRE absorption into the bloodstream. Hematological, biochemical parameters and microscopic examination of heart, liver and kidney were evaluated. Results: IRE demonstrated no cytotoxicity toward hepatocytes and skeletal muscle cells and facilitated glucose consumption into cells. In the acute toxicity study, on day 14, after a single oral administration of 2000 mg/kg IRE, no mortality and behavioral alterations. There was no change in metabolic parameters. Histopathology of heart, liver and kidney showed normal architecture. Conclusions: Thus, LD50 of IRE was considered superior to 2000 mg/kg. Hence the extract can be utilized safely and could provide a capability for diabetic control.

Objective: The current study was designed to investigate the protective effects of curcuma caplet against titanium dioxide nanoparticles (nTiO2)-induced damage in liver and kidney of male Wistar rats.Materials and Methods: Thirty adult (7-8 week old) male rats (200 g) were randomly divided into 5 groups of 6 each. The first and second groups received olive oil and nTiO2 (300 mg/kg body weight) as control and nTiO2 groups, respectively. The third, fourth, and fifth groups received Curcuma at concentrations of 100, 200, and 300 mg/kg body weight in addition to 300 mg/kg body weight of nTiO2, respectively. The treatment was performed through gavage for 3 weeks. Rats' blood was examined for total antioxidant capacity (TAC), total oxidant status (TOS), and malondialdehyde (MDA) levels as well as antioxidant enzymes superoxide dismutase (SOD), and glutathione peroxidase (GPx), and activity of liver enzymes alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and renal factors (urea, uric acid, and creatinine). Histological analyses were also performed to estimate the extent of hepatic and renal injury.Results: nTiO2-induced liver and kidney damage by decreased serum SOD, GPx, and TAC (p

Background: This study examined the use of solid lipid nanoparticles (SLNs) to administer Dacarbazine (DTIC) to skin melanoma cells with minimal adverse effects. Melanoma is a tricky skin cancer to cure, and standard chemotherapy has many negative effects. Encapsulating DTIC in SLNs may allow the drug to target melanoma cells without harming healthy cells. The study developed and tested DTIC-loaded SLNs for skin melanoma treatment. Methods: This study encapsulated Dacarbazine (DTIC) in solid lipid nanoparticles (SLNs). SLNs with reversed micelles were produced utilizing specified ratios of the surfactant Kolliphor® P188 and phosphatidylcholine. To track SLN drug localisation, gold nanoparticles were conjugated to the DTIC. Nanoparticle size and form were examined using DLS and TEM. These approaches ensured SLNs had the correct size and shape for drug delivery. Significant findings: In the study, various parameters of the developed solid lipid nanoparticles (SLNs) were evaluated, including particle size, zeta potential, polydispersity index (PDI), entrapment efficacy, and cumulative drug permeation. The values for these parameters varied across the different formulations, with particle size ranging from 146 ± 4.71 nm to 715 ± 7.36 nm, zeta potential from -12.45 ± 2.78 mV to -30.78 ± 2.83 mV, PDI from 0.17 ± 0.013 to 0.51 ± 0.023, entrapment efficacy from 37.78 ± 2.78% to 87.45 ± 4.78%, and cumulative drug permeation from 117 ± 4.77 mg/cm2 to 275 ± 5.67 mg/cm2. To determine the optimal anti-cancer formulation, the DTIC-SLNs-8 nanoparticles were mixed with an optimized concentration of Gellan gum (0.01% w/v) and applied to DMBA-induced skin tumors in rats for six weeks, twice daily. Histopathology demonstrated that DTIC-SLNs-8-treated rats had less keratosis, inflammatory responses, and angiogenesis than free DTIC-treated rats. The development of SLNs may be a promising approach for melanoma treatment due to their improved drug retention over the skin. The optimised anticancer formulation DTIC-SLNs-8 showed improved efficacy with minimal side effects as compared to free DTIC. [ABSTRACT FROM AUTHOR]

Aging is associated with muscle atrophy, and erosion and destruction of neuronal pathways in the spinal cord. The study aim was to assess the effect of swimming training (Sw) and L-arginine loaded chitosan nanoparticles (LA-CNPs) on the sensory and motor neuron population, autophagy marker LC3, total oxidant status/total antioxidant capacity, behavioural test, GABA and BDNF-TrkB pathway in the spinal cord of aging rats. The rats were randomized to five groups: young (8-weeks) control (n = 7), old control (n = 7), old Sw (n = 7), old LA-CNPs (n = 7) and old Sw + LA-CNPs (n = 7). Groups under LA-CNPs supplementation received 500 mg/kg/day. Sw groups performed a swimming exercise programme 5 days per week for 6 weeks. Upon the completion of the interventions the rats were euthanized and the spinal cord was fixed and frozen for histological assessment, IHC, and gene expression analysis. The old group had more atrophy in the spinal cord with higher changes in LC3 as an indicator of autophagy in the spinal cord compared to the young group (p < 0.0001). The old Sw + LA-CNPs group increased (improved) spinal cord GABA (p = 0.0187), BDNF (p = 0.0003), TrkB (p < 0.0001) gene expression, decreased autophagy marker LC3 protein (p < 0.0001), nerve atrophy and jumping/licking latency (p < 0.0001), improved sciatic functional index score and total oxidant status/total antioxidant capacity compared to the old group (p < 0.0001). In conclusion, swimming and LA-CNPs seems to ameliorate aging‐induced neuron atrophy, autophagy marker LC3, oxidant-antioxidant status, functional restoration, GABA and BDNF-TrkB pathway in the spinal cord of aging rats. Our study provides experimental evidence for a possible positive role of swimming and L-arginine loaded chitosan nanoparticles to decrease complications of aging. [ABSTRACT FROM AUTHOR]

Influenza virus can infect the vascular endothelium and cause endothelial dysfunction. Persons at higher risk for severe influenza are patients with acute and chronic cardiovascular disorders; however, the mechanism of influenza-induced cardiovascular system alteration remains not fully understood. The aim of the study was to assess the functional activity of mesenteric blood vessels of Wistar rats with premorbid acute cardiomyopathy infected with Influenza A(H1N1)pdm09 virus. For this, we determined (1) the vasomotor activity of mesenteric blood vessels of Wistar rats using wire myography, (2) the level of expression of three endothelial factors: endothelial nitric oxide synthase (eNOS), plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (tPA) in the endothelium of mesenteric blood vessels using immunohistochemistry, and (3) the concentration of PAI-1 and tPA in the blood plasma using ELISA. Acute cardiomyopathy in animals was induced by doxorubicin (DOX) following infection with rat-adapted Influenza A(H1N1)pdm09 virus. The functional activity of mesenteric blood vessels was analyzed at 24 and 96 h post infection (hpi). Thus, the maximal response of mesenteric arteries to both vasoconstrictor and vasodilator at 24 and 96 hpi was significantly decreased compared with control. Expression of eNOS in the mesenteric vascular endothelium was modulated at 24 and 96 hpi. PAI-1 expression increased 3.47-fold at 96 hpi, while the concentration of PAI-1 in the blood plasma increased 6.43-fold at 24 hpi compared with control. The tPA concentration in plasma was also modulated at 24 hpi and 96 hpi. The obtained data indicate that influenza A(H1N1)pdm09 virus aggravates the course of premorbid acute cardiomyopathy in Wistar rats, causing pronounced dysregulation of endothelial factor expression and vasomotor activity impairment of mesenteric arteries. [ABSTRACT FROM AUTHOR]

A dopamine derivative, 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, known as salsolinol (SAL), has increasingly gained attention since its first detection in the urine of Parkinson's disease patients treated with levodopa, and has been proposed as a possible neurotoxic contributor to the disease. Yet, so far, the neurobiological role of SAL remains unclear. Thus, the main aims of our study were to compare the neurotoxic potential of SAL with MPP+ (1-methyl-4-phenylpyridinium ion) in vitro, and to examine intestinal and metabolic alterations following intraperitoneal SAL administration in vivo. In vitro, SH-SY5Y neuroblastoma cell line was monitored following MPP+ and SAL treatment. In vivo, Wistar rats were subjected to SAL administration by either osmotic intraperitoneal mini-pumps or a single intraperitoneal injection, and after two weeks, biochemical and morphological parameters were assessed. SH-SY5Y cells treated with MPP+ (1000 μM) and SAL (50 µM) showed increase in cell viability and fluorescence intensity in comparison with the cells treated with MPP+ alone. In vivo, we predominantly observed decreased collagen content in the submucosal layer, decreased neuronal density with comparable ganglionic area in the jejunal myenteric plexus, and increased glial S100 expression in both enteric plexuses, yet with no obvious signs of inflammation. Besides, glucose and triglycerides levels were lower after single SAL-treatment (200 mg/kg), and low- to high-density lipoprotein (LDL/HDL) ratio and aspartate to alanine aminotransferases (AST/ALT) ratio levels were higher after continuous SAL-treatment (200 mg/kg in total over 2 weeks). Low doses of SAL were non-toxic and exhibited pronounced neuroprotective properties against MPP+ in SH-SY5Y cell line, which supports the use of SAL as a reference compound for in vitro studies. In vivo results give insight into our understanding of gastrointestinal remodeling following intraperitoneal SAL administration, and might represent morphological correlates of a microglial-related enteric neurodegeneration and dopaminergic dysregulation. [ABSTRACT FROM AUTHOR]

This study aimed to analyze the biochemical, histological, and gene expression alterations produced in a hepatocarcinogenesis model induced by the chronic administration of diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) in Wistar rats. Thirteen rats weighing 180 to 200 g were divided into two groups: control and treated. Rats in the treated group were administered an intraperitoneal (i.p.) injection of DEN (50 mg/kg/week) and an intragastric (i.g.) dose of 2-AAF (25 mg/kg/week) for 18 weeks. The treated group had significant increases in their total cholesterol, HDL-C, AST, ALT, ALKP, and GGT levels. Furthermore, a histological analysis showed the loss of normal liver architecture with nuclear pleomorphism in the hepatocytes, atypical mitosis, and fibrous septa that were distributed between the portal triads and collagen fibers through the hepatic sinusoids. The gene expressions of 24 genes related to fibrosis, inflammation, apoptosis, cell growth, angiogenesis, lipid metabolism, and alpha-fetoprotein (AFP) were analyzed; only TGFβ, COL1α1, CYP2E1, CAT, SOD, IL6, TNF-α, and ALB showed significant differences when both groups were compared. Additionally, lung histopathological alterations were found in the treated group, suggesting metastasis. In this model, the chronic administration of DEN+2-AAF induces characteristic alterations of hepatocellular carcinoma in Wistar rats without AFP gene expression changes, highlighting different signatures in hepatocellular carcinoma heterogeneity. [ABSTRACT FROM AUTHOR]

Species of the genus Acanthamoeba are free-living protozoans that occasionally act as parasites, causing a severe, progressive corneal infection termed Acanthamoeba keratitis (AK). The variable pathogenic potential among Acanthamoeba lineages has been shown by in vitro assays, but little is known about the behavior of different strains in animal models of AK. This work aimed to evaluate the infectivity of Acanthamoeba from distinct morphological groups and genotypes in a rat model of AK and apply an immunohistochemical technique for histological characterization of the lesions. Only a strain classified as group I/genotype T17, isolated from a soil source, caused ulcerated corneal lesions in two Wistar rats (n = 9) subjected to intrastromal inoculation. Two strains derived from AK human cases (group II/genotype T4 and group III/genotype T5) did not induce corneal lesions in the rats. A previous association of group II/genotype T4 trophozoites with lethally irradiated Escherichia coli did not influence the infectivity. A hyperimmune serum produced in Wistar rats was validated by an immunocytochemical technique using the three distinct strains and then applied for immunohistochemistry. The abundance of antigenic residues was observed in both corneas with keratitis, suggesting that the infectious process tended to resolve. Despite the low infection rate of the AK Wistar rat model, we produced an immunochemical tool with a potential diagnostic application. We also showed for the first time the ability of Acanthamoeba from T17 genotype to cause AK in experimental conditions. [ABSTRACT FROM AUTHOR]

The pharmacokinetics of succinate was studied in Wistar rats after a single intravenous administration of Mexidol in a dose 100 mg/kg body weight. The concentration of succinate in blood plasma, cytoplasmic and mitochondrial fractions of cells of the cerebral cortex, left-ventricular myocardium, and liver was measured by HPLC-MS/MS. After single intravenous administration of Mexidol, succinate was evenly distributed in organs and tissues and quickly eliminated from the body. The pharmacokinetics of succinate was described by a two-chamber model. An increase in the level of succinate in the cytoplasmic fraction of the liver, myocardium, and cerebral cortex cells and a minor increase in the mitochondrial fraction were observed. The maximum increase in the level of succinate in the cytoplasmic fraction was observed in the liver tissue, a less pronounced elevation was observed in the cerebral cortex and myocardium; no significant differences between the cerebral cortex and myocardium were observed by this parameter. [ABSTRACT FROM AUTHOR]

This study aimed to determine the potential of quercetin and Zingiber officinale (ZO) Roscoe extract to alleviate the renal damage induced by dimethoate (DM) and fluoride (F-) alone and by their combined exposure in rats. A total of 54 adult Wistar rats were randomly allocated to nine groups (n = 6). A sub-lethal dose of DM (1/10th of the median lethal dose) was administered by oral gavage alone and along with F- (4.5 ppm, three-fold the permissible limit) in their drinking water continuously for 28 days. Chromatographical analysis revealed the presence of quercetin, curcumin, and other phytochemicals with strong antioxidant properties in ZO-rhizome extract. Severe changes were observed in the levels of the renal biomarkers and histoarchitecture after co-administration of the toxicants, indicating greater kidney damage. The administration of ZO extract (300 mg/kg) along with either or both toxicants led to a significant restoration of the biochemical markers and renal antioxidant profile and histology. [ABSTRACT FROM AUTHOR]

Starch hyaluronate is used as a new superdisintegrating agent in the development of fastdissolving tablets of poorly soluble drugs because of its improved biocompatibility, and hydrophilicity. The purpose of this study is to assess the acute and subacute toxicity profiles of starch hyaluronate in Wistar rats. The starch hyaluronate was administered to Wistar rats in a single-dose acute study and monitored for seven days. Wistar male and female rats were used in a 28-day sub-acute study that examined the effects of oral doses of 100, 200, and 600 mg/kg body weight/day on body weight, food intake, mortality, biochemical analysis, and histopathological evaluation. An acute study revealed that the synthesized starch hyaluronate minimal oral fatal dose for rats was larger than 2000 mg/kg body weight. The subacute toxicity evaluation found no significant changes when compared to the control group, and there was no change in hematological or biochemical parameters. The weights of the liver, kidneys, and pancreas remained constant. Based on the findings, it was concluded that starch hyaluronate at 600mg/kg body weight/day was neither immunogenic nor sensitizing, and was not a reproductive or developmental toxicant, implying that it is relatively safe when taken orally. [ABSTRACT FROM AUTHOR]

Anthracycline doxorubicin (DOX) is still widely used as a chemotherapeutic drug for some solid tumors. Although DOX is highly effective, its side effects are limiting factors, such as cardio, nephro and hepatotoxicity. As such, approaches used to mitigate these adverse effects are highly encouraged. Omega 3 (ω-3), which is a class of long-chain polyunsaturated fatty acids, has been shown to have anti-inflammatory and antioxidant effects in preclinical bioassays. Thus, we evaluated the protective effects of ω-3 supplementation on hepatotoxicity and nephrotoxicity induced by multiple DOX administrations in rodents. Male Wistar rats (10 rats/group) were treated daily with ω-3 (400 mg/kg/day) by gavage for six weeks. Two weeks after the first ω-3 administration, the rats received DOX (3.5 mg/kg, intraperitoneal, 1×/week) for four weeks. DOX treatment reduced body weight gain increased systemic genotoxicity and caused liver-related (increase in serum ALT levels, thickness of the Glisson's capsule, compensatory proliferation and p65 levels) and kidney-related (increase in serum urea and creatinine levels, and incidence of tubular dilatation) deleterious outcomes. In contrast, ω-3 supplementation was safe and abrogated the DOX-related enhancement of systemic genotoxicity, serum urea and creatinine levels. Furthermore, ω-3 intervention reduced by 50% the incidence of kidney histological lesions while reducing by 40–50% the p65 protein level, and the proliferative response in the liver induced by DOX. Our findings indicate that ω-3 intervention attenuated the DOX-induced deleterious effects in the liver and kidney. Therefore, our findings may inspire future mechanistical investigations and clinical interventions with ω-3 on the reported outcomes. [ABSTRACT FROM AUTHOR]

Background and Objective: Understanding the cellular signaling mechanisms involved in muscle hypertrophy is considered a scientific challenge. Mammalian target of rapamycin (mTOR) is one of the regulatory factors in this process that increases protein synthesis in skeletal muscle through phosphorylation. This study aimed to determine the effect of six weeks of highintensity interval training (HIIT) on phosphorylated mTOR protein in the quadriceps muscles of adult male Wistar rats. Methods: In this experimental study, 16 adult male Wistar rats (six weeks old and weighing an average of 190.93±4.97g) were used. The animals were randomly divided into two groups of control and training (n=8). The training group underwent six weeks of HIIT on a treadmill, with five sessions per week. The load was increased during the six weeks from repeating the interval of 30 meters per minute for 30 seconds in the first sessions to eleven repetitions of the interval of 35 meters per minute for 30 seconds at the end of the sixth week, with rest intervals between the intervals at a speed of 13 meters per minute for 60 seconds. The control group did not undergo any training. The mice were anesthetized, and the Vastus lateralis of the quadriceps muscle was extracted. The level of phosphorylated mTOR protein in the quadriceps muscle was measured using the immunohistochemical method. Results: HIIT significantly increased the levels of mTOR phosphorylation protein in male Wistar quadriceps femoris muscle compared to the control group (P<0.05). Conclusion: Interval activity can have a positive effect on muscle hypertrophy through mTOR. [ABSTRACT FROM AUTHOR]

Introduction: in the study of diabetes mellitus it is essential to use experimental models that help to understand the particularities of the disease in humans. Objective: to describe the effects of zinc supplementation on pancreatic islet morphometry in pregnant Wistar rats with moderate diabetes. Methods: a descriptive, cross-sectional, experimental study with quantitative approach was performed from January 2016 to December 2018. Histological slides of pancreas were analyzed from 32 rats randomly distributed in four experimental groups which were induced diabetes mellitus with streptozotocin and treated with zinc sulfate. The ANOVA parametric test was applied and a 95% confidence interval was used. Results: an increase in the mean number of islets was observed in all groups with respect to the control group. The highest mean value for both the largest and smallest islet diameter was in the diabetic-Zn and control-Zn groups, respectively. The highest mean area was in the control-Zn group and the highest circularity was shared by the diabetic and diabetic-Zn groups. Conclusions: during the study there were no significant differences in the number, the largest diameter and the circularity of the pancreatic islets between the study groups. No significant effects of zinc supplementation on any of the morphometric parameters studied were found. [ABSTRACT FROM AUTHOR]

Oral epithelial dysplasia (OED) is the most important stage of change and is called a reversible premalignant lesion. Pegagan (Centella asiatica (Linn.) Urban) is one of the herbal plants widely utilized and has the potential cancer chemoprevention agent. This study aimed to determine the effect of Centella asiatica ethanol extract in inhibiting the progression of buccal mucosal dysplasia lesions in Wistar rats histologically with HE staining. This study is a laboratory experiment with a post-test-only control group design. A total of 28 male Wistar rats were divided into four groups: the control group without treatment and the treatment group were given different doses of Centella asiatica extract (375 mg/kgBW, 750 mg/kgBW, 1500 mg/kgBW) for 61 days. On day 29, all groups of rats had their buccal mucosa induced with 0.5% DMBA three times a week for four weeks. On day 61, all rats were sacrificed, and buccal mucosa samples were examined histopathologically with HE staining. The degree of dysplasia was assessed by scoring based on the WHO 2017 classification. The data were analyzed using the Kruskal-Wallis test and Mann-Whitney test. The results showed that the average score of the highest degree of dysplasia in the control group (1.63 ± 0.51), then sequentially followed by the treatment group doses of 375 mg/kgBW, 750 mg/kgBW and 1500 mg/kgBW. Statistical tests showed significant differences in all groups (p <0.05). There was a significant difference between the 750 mg/kgBW group and the control group (p<0.05) and the 1500 mg/kgBW group with the control group (p<0.05). The administration of high doses of Centella asiatica ethanol extract, namely 750 mg/kgBW and 1500 mg/kgBW, effectively inhibited the progression of buccal mucosal dysplasia lesions in Wistar rats induced with DMBA. In other words, Centella asiatica has the potential as a chemoprevention agent. [ABSTRACT FROM AUTHOR]

Indoxacarb is a novel organophosphate substitute and is considered a "lower risk" pesticide in agriculture. However, in humans and animals, indoxacarb exposure had been linked to substantial health problems. This study was carried out to investigate the acute oral toxicity and histopathological changes of indoxacarb in female Wistar albino rats. The acute oral toxicity of indoxacarb was performed as per the OECD guidelines No. 425, (Acute Oral Toxicity - Up-anddown procedure). The LD50 of indoxacarb was estimated using AOT425StatPgm (version: 1.0) statistical program and found to be 1098 mg/kg. Hence the pesticide is categorized as Type II class of pesticide according to the WHO standards. All the animals dosed at 2000 mg/kg died within 12 h exhibiting clinical signs of intermittent episodes of tremors, incoordination, respiratory distress and open-mouth breathing. Histopathological examination of indoxacarb treated rats at 2000mg/kg degeneration of hepatocytes and necrosis in haematoxylin and eosin staining. [ABSTRACT FROM AUTHOR]

Mehani, a polyherbal formulation (PHF) containing five herbs has been used in the diabetes treatment for more than 20 years in India. Few data are available for its polypharmacological properties in treating interlinked diseases. Hence, the present study investigates the in vitro and in vivo antidiabetic and associated anti-inflammatory activity of Mehani. Glucose uptake activity of aqueous and hydroalcoholic extracts of PHF, individual herbs and sub fractionations (alkaloid, polyphenol) were evaluated in C2C12 mouse skeletal muscle cells. In vitro antidiabetic enzymatic assay, anti glycation activity was assessed for all the extracts. Active compounds were determined using HPLC analysis. Genes involved in glucose uptake and inflammatory pathways at mRNA level, GLUT4 protein expression and translocation were analyzed. Also, In vivo hypoglycemic, hypolipidemic and antioxidant activities were investigated in the best acting extracts in diabetic wistar rats. Aqueous (AQF) and polyphenolic (PPF) extracts showed insulin stimulated glucose uptake of 2.2±0.26 and 2.0±0.13 fold when compared to the untreated control. AQF exerted anti hyperglycemic action on GLUT4 via PI3K-AKT pathway, while PPF via AMPK pathway. Both inhibited the LPS induced activation of TNFα, IL6 and IL10 cytokines at mRNA level. Particularly, AQF showed increased GLUT4 protein expression and translocation. Gallic acid, cinnamic acid derivatives and D-pinitol (new finding) were the major bioactives identified through HPLC analysis. AQF (400 mg/kg b.w) treated diabetic rats showed significant reduction in blood glucose, HbA1c levels after 21 days of treatment. Increased serum cholesterol (67.5± 3.53 mg/dL), TGL (123.5±3.53) levels in diabetic rats were significantly reduced in AQF treated rats. Also, improvement in the antioxidant levels (SOD, CAT, GSH and GST) with reduction in liver enzymes was observed. AQF possessed hepatoprotective and renoprotective activities and efficiently restored the pancreatic beta cell integrity. To conclude, aqueous Mehani extract can be used as a safe, complimentary medicine to treat diabetes and associated diseases. [Display omitted] • The polypharmacological properties of Mehani formulation is investigated here • In vitro study shows that Aqueous (AQF) and polyphenolic (PPF) Mehani extract exerted anti-hyperglycemic action on GLUT4 via PI3K-AKT pathway and AMPK pathway respectively in C2C12 cells. Particularly AQF increased the GLUT4 expression and translocation. • Both inhibited the LPS induced activation of TNFα, IL6 and IL10 cytokines RAW 264.7 cells. • Gallic acid, cinnamic acid derivatives and D-pinitol (new finding) were the major bioactives identified through HPLC analysis • AQF (400 mg/kg b.w) possessed In vivo hypoglycemic, hypolipidemic and antioxidant activities in diabetic wistar rats. [ABSTRACT FROM AUTHOR]

Introduction: changes in dietary/energetic composition during the critical period of development (pregnancy/lactation) or even during mealtimes may contribute to changes in metabolic and behavioral parameters such as feeding behavior. Objective: the study aimed to examine the repercussions of time-restricted feeding on feeding behavior and on some parameters of glycemic and lipemic metabolism of the offspring of adult rats whose mothers were fed a westernized diet during pregnancy and lactation. Methods: initially, 43 male Wistar rats were used. At 60 days of life, the rats were divided into 4 groups: C: control group; RC: control group with time-restricted feeding; W: westernized diet during pregnancy/lactation group; RW: westernized diet group during pregnancy/lactation group with time-restricted feeding. The following parameters were evaluated: behavioral sequence of satiety (BSS), biochemical parameters, and abdominal fat. Results: findings highlighted a high level of abdominal fat in the groups whose mothers were submitted to a westernized diet, as well as hypertriglyceridemia, and clear differences in feed rate and meal length. This study showed that the westernized diet ingested by mothers during pregnancy and lactation induced hyperlipidemia and changes in the feeding behavior of their adult offspring. Conclusions: these changes may be responsible for eating disorders and risk factors for metabolism disturbance-related diseases. [ABSTRACT FROM AUTHOR]

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Background: To investigate the potential anti-obesity properties of an innovative functional formula (called the Mei-Gin formula: MGF) consisting of bainiku-ekisu, Prunus mume (70% ethanol extract), black garlic (water extract), and Mesona procumbens Hemsl. (40% ethanol extract) for reducing lipid accumulation in 3T3-L1 adipocytes in vitro and obese rats in vivo. Material and Methods: The prevention and regression of high-fat diet (HFD)-induced obesity by the intervention of Japan Mei-Gin, MGF-3 and -7, and positive health supplement powder were investigated in male Wistar rats. The anti-obesity effects of MGF-3 and -7 in rats with HFD-induced obesity were examined by analyzing the role of visceral and subcutaneous adipose tissue in the development of obesity. Results: The results indicated that MGF-1-7 significantly suppressed lipid accumulation and cell differentiation through the down-regulation of GPDH activity, as a key regulator in the synthesis of triglycerides. Additionally, MGF-3 and MGF-7 exhibited a greater inhibitory effect on adipogenesis in 3T3-L1 adipocytes. The high-fat diet increased body weight, liver weight, and total body fat (visceral and subcutaneous fat) in obese rats, while these alterations were effectively improved by the administration of MGF-3 and -7, especially MGF-7. Conclusion: This study highlights the role of the Mei-Gin formula, particularly MGF-7, in anti-obesity action, which has the potential to be used as a therapeutic agent for the prevention or treatment of obesity. [ABSTRACT FROM AUTHOR]

Nanoparticles are vastly exploited in today's technology. However, it is realized that exposure to high concentrations of nanoparticles (NPs) may have adverse effects on human health. According to previous reports, zinc oxide (ZnO) NPs cause toxic effects in tissues via inducing apoptosis. The current work was designed to evaluate possible protective activities of vitamins (Vits) A, C, and E against ZnO NPs-induced apoptosis in the liver of rats. To this aim, fifty-four adult male Wistar rats were randomly distributed into nine groups (n = 6 rats for each group), namely, Control1 (water), Control2 (olive oil), Vit A (1000 IU/kg), Vit C (200 mg/kg), Vit E (100 IU/kg), ZnO (200 mg/kg), ZnO + VitA, ZnO + VitC, and ZnO + VitE. To investigate apoptosis, the mRNA and protein expression of Bcl-2-associated X (Bax) and B-cell lymphoma protein 2 (Bcl-2) were examined by qRT-PCR and western blot techniques. The mRNA and protein expression of TNF-α as well as the activity of caspase 3,7 were also measured. The results revealed that ZnO NPs considerably enhance the ratio of Bax to Bcl-2 mRNA and protein expression as well as the activity of caspase 3,7 compared to the control group. Furthermore, the findings implied that the elevated level of TNF-α may link with ZnO NPs-mediated apoptosis in the liver of rats. More importantly, Vits A, C, and E exhibited ameliorative properties against apoptosis-inducing effects of ZnO NPs. Thus, administration of Vits A, C, and E may be effective in preventing liver damage and apoptosis caused by ZnO NPs. [ABSTRACT FROM AUTHOR]

Abstract Biological activity of boron-containing compounds (BCCs) has been well-known. Growing interest and numerous applications for BCCs have been reported. Boron and boron-containing acids show low acute toxicity in mammals but data on halogenated boroxine (HB) - dipotassium-trioxohydroxytetrafluorotriborate, K2(B3O3F4OH) acute toxicity have not been reported before. This compound, characterized as a potential therapeutic for skin changes, exhibits no observable genotoxicity in doses lower that 0.1 mg/ml in vitro and 55 mg/kg in vivo. It has also been confirmed as an antitumour agent both in vitro and in vivo as well as an inhibitor of enzymes involved in antioxidant mechanisms. The aim of this study was to assess the acute toxicity of HB and to determine the maximum tolerated dose as well as a dose free of any signs of toxicity in different test organisms. Acute toxicity of HB was tested in Sprague-Dawley and Wistar rats and BALB/c mice after single parenteral application of different doses. We determined doses free of any sign of toxicity and LD50 after single dose administration. LD50 of HB ranges from 63 to 75 mg/kg in different test models, meaning that HB shows moderate toxicity.

Background: Cardiometabolic disease is becoming a main cause of death worldwide with over ten million fatalities annually. Lithium (Li) has been reported to be one of the major causes of cardiometabolic disorders due to its narrow therapeutic index. Sodium butyrate (NaB) which is a short chain fatty acid is implicated to possess an amazing therapeutic effect against cardiometabolic disorders. As a result, the current study aims to evaluate sodium butyrate impact on lithium-induced cardiometabolic disorders. Methods: Twenty male Wistar rats weighing between 230 and 250 g were used for the experiment. They were grouped into control and treated groups respectively as (CTR; normal chow), Lithium only (Li; 5 mg/kg, po), Sodium butyrate only (NaB) (200 mg/kg, po) and NaB +Lithium (Li; 5 mg/kg +NaB; 200 mg/kg, po) for six weeks, after a week of acclimation; n=5. The animals were anesthetized using sodium pentobarbital at a dose of 50 mg/kg intraperitoneally, blood samples were collected by cardiac puncture and cardiac tissue homogenates were measured for plasma Fasting Blood Sugar (FBS), plasma Insulin, Phosphatidylinositol 3 Kinase (PI3K), Nitric oxide (NO), Glucose-6-phosphate dehydrogenase (G6PDH), Malonyladehyde (MDA), Catalase (CAT), Superoxide Dismutase (SOD), Nicotinamide adenine dinucleotide phosphate (NADPH), Glutathione Peroxidase (GPx), and Adenosine deaminase /Xanthine oxidase /uric acid (ADA/XO/UA) using respective ELISA kits. Results: The results showed that lithium significantly increased fasting blood sugar (FBS), plasma insulin, GPx, CAT, SOD, and MDA while causing a statistical reduction in plasma and cardiac concentration of NADPH, G6PDH, PI3K, endothelial nitric oxide synthase (eNOS), and Nitric Oxide (NO) in comparison with the control. However, butyrate attenuated plasma GPx, CAT, SOD, MDA, FBS, plasma insulin and significantly elevated plasma and cardiac PI3K, eNOS, NO, plasma NADPH and G6PDH levels in relation to control. Also no change was observed in the plasma and cardiac ADA/XO/UA following sodium butyrate. Conclusion: Therefore, butyrate has a remarkable therapeutic potential in ameliorating lithium induced cardiometabolic disorders through glucometabolic control.

Objectives: As a universal cytoprotective protein, Hsp70 is used to monitor the effects of environmental temperature changes, increasing the survival rate of cells exposed to stress, as well as the role of protein in cardiovascular disease, body decay and cell aging. Our research aims to to examine whether changes in serum protein 70 (Hsp70) values due to exposure to water temperature (41 °C and 44 °C) may indicate a mechanism of cardiomyocyte damage due to hyperthermia. Methods: A total of 40 adult albino Wistar rats, of known gender and body weight from 250 g to 300 g were used as material in this research. Rats were housed in polypropylene cages with optimum environmental conditions. Depending on the temperature of the water (WT) to which they were exposed, rats were randomized into the following groups.WT 37 °C (n = 8); WT 41 °C, antemortem (n = 8), WT 41 °C, postmortem (n = 8); WT 44 °C, antemortem (n = 8), WT 44 °C, postmortem (n = 8). Blood samples for determination of Hsp70 were taken before and after the expiration of the given duration of the experiment of 20 min or death. The Hsp70 level was determined by Enzyme-Linked Immunosorbent Assay (ELISA) Results: Hsp70 basal values in serum were significantly different, p = 0.004 pg/ml, and in the groups depending on the duration of exposure to Hsp70, p = 0.002. Serum Hsp70 values after being exposed to water temperature were significantly different according to the group, p = 0.009. Significant lower Hsp70 levels were found in the control group according to G41 p = 0.006 and G44, p = 0.002. Insignificant differences in Hsp70 level were found among theseG41 and G44, p > 0.005. The concentration of Hsp70 in rat serum and ≥ 31.36 ng/ml indicates exposure to temperatures higher than 37 °C (sensitivity 85.71%, specificity 83.33%, PPV 96%, and NPV 55%, p = 0.002). Conclusions: Altered concentration of serum Hsp70 may show exposition to the elevated water temperature.

Background and Objectives: Cadmium (Cd) can induce lipid peroxidation, increase malondialdehyde (MDA), and reduce total oxidative capacity (TAC) in the testis by producing free radicals and, as a result, cause infertility. This study aims to determine the effect of a period of endurance exercise on MDA levels and TAC of testicular tissue in adult male rats with infertility induced by cadmium chloride. Methods: In this experimental study, 32 healthy adult male Wistar rats weighing 250±30 g and aged 12 weeks were used, which were randomly divided into four groups of control (n=8), exercise (n=8), Cd (n=8), and Cd+exercise (n=8). The endurance exercise program was presented at five sessions per week for 5 weeks. Data were analyzed in SPSS software, version 24 using one-way analysis of variance and by the Least Significant Difference post hoc test. The significance level was set at 0.05. Results: The MDA and TAC in the exercise group were increased significantly compared to the control group (P

Background and Objective: Multiple sclerosis (MS) is a common neurological disease that increases oxidative stress and causes immune system disorders. Curcumin is the active component of turmeric with anti-inflammatory properties. This study was conducted to determine the effects of curcumin on cortisol, catalase, and nerve growth factor (NGF) expression in an animal model of MS. Methods: This experimental study was conducted on 30 female Wistar rats. Experimental autoimmune encephalomyelitis (EAE) was chosen as an experimental model of MS. The rats were divided into 3 groups of 10, including a healthy control group, an affected group, and a group treated with curcumin. The disease was induced by immunization of rats with homogenized guinea pig spinal cord and Freund's complete adjuvant. Then, the immunized animals were allocated into two equal groups. Treatment with curcumin (100 mg/kg daily) was started 12 days after the immunization when the rats showed the first symptoms of neurologic disability. The treatment was continued until day 24 post-immunization. Simultaneously, the EAE group received the medicine solvent (distilled water). Finally, the rats' weights as well as cortisol, catalase, and NGF levels were measured in the study groups. Results: Curcumin significantly increased the level of cortisol to a level equal to that of healthy rats (P

Pregnancy-specific beta-1-glycoprotein (PSG) is a protein with pleiotropic biological effects, particularly immunoregulatory and immunosuppressive potential. The use of recombinant PSG may exert therapeutic effects in experimental animals with induced autoimmune diseases. Recently, a search for the biological effects of short linear motifs (SLiMs) has become a new strategy for designing the pharmacological compounds. Tetrapeptide regions have been identified in the primary structure of several PSGs: YQCE, YECE and YACS, these SLiMs exhibit immunomodulatory activity. The aim of our study was to evaluate the prospectives for usage of PSG peptide fragments as pharmacological agents to modulate transplant immunity. We used an original model of host-versus-graft response in male Wistar rats transplanted with bone marrow, without prior conditioning treatment of recipients. We used a cocktail of the PSG peptide fragments administered to Wistar rats in the course of allogeneic bone marrow transplantation (BM) in dynamic manner, evaluating the cytokine profile as an integral index of immune response. Cytokine levels were determined by multiplex method using Bio-Plex ProTM Rat 23-Plex kit. Statistical processing of the data was performed by means of two-way analysis of variance and Tukey’s post hoc test for multiple comparisons. We have found that the levels of pro-inflammatory cytokines (IFNγ, IL-1α, IL-1β, IL-18), as well as the contents of G-CSF, GM-CSF and IL-7 were increased in the animals injected with BM only. In the group of animals injected with BM + PSG peptides, an increase in IFNγ, IL-6, TNFα was observed, which decreased by the end of the experiment. Increased levels of antiinflammatory cytokines IL-4 and IL-13 were detected in blood serum of the animals on day +14. Moreover, administration of PSG peptides also led to increase in IL-2, M-CSF, MCP-1, and RANTES levels on day 14 from the beginning of the experiment, and to a gradual decrease in their levels till the end of the experiment. Meanwhile, control group showed a marked tendency for increase of these and other cytokines. Thus, it was shown that the use of PSG peptides upon development of immune response to BM allograft may promote a return to normal levels for the most cytokines studied, thus presuming the immunopharmacological potential of these peptides. The obtained data can be used to develop a pharmacological preparation of the studied peptides to correct the imbalance of immune system.

This study investigated the effect of high intensity interval training on CTGF and RXFP1 genes expression of heart tissue and SGPT liver enzyme in rats with fatty liver. 48 male Wistar rats (200-250 g) were divided randomly into the following 6 groups: Healthy base group (BH), base Steatosis group (BS), Healthy HIIT group (HIIT), Steatosis HIIT group (SHIIT), Healthy control group (CH), control Steatosis group (CS). Rats in the fatty liver group received oral tetracycline daily for two weeks. Rats in the training groups were also trained for 5 weeks / five days. Both BS and BH groups sacrificed at the end of the 2nd week. CS and training groups sacrificed at the end of 5th week and heart tissue samples were taken to examine CTGF, RXFP1, and SGPT genes expression. The results of the study showed that he amounts of SGPT in BS and CS groups were meaningfully higher than those in the other 4 groups. The level of this enzyme in SHIIT and HIIT groups was significantly lower than that in the fatty liver groups. The RXFP1 gene expression in CS, BS and SHIIT groups were significantly higher than those in the other 3 groups. Thus, it can be claimed that fatty liver increased cardiac fibrosis factors but by reducing these factors HIIT was able to prevent the process of cardiac fibrosis from liver Steatosis; therefore, HITT can be used as a new method to Cardiac rehabilitation of patients.

Objectives. To obtain the most detailed data on the dynamics of the mRNA level of the Tweak/Fn14 signaling pathway genes at morphologically confirmed stages of liver fibrogenesis using the Ishak K.G. semi-quantitative scale. Material and methods. Liver fibrogenesis in Wistar rats was induced with thioacetamide at a dose of 200 mg/kg animal weight twice a week during 17 weeks. Real-time PCR was used to study the level of mRNA of the tweak and fn14 genes. Liver sections were stained with hematoxylin and eosin, as well as by the Mallory method. Fibrosis stage was assessed using the Ishak K.G. semi-quantitative scale. Results. After three weeks of the experiment (the degree of fibrosis according to the Ishak K.G. scale corresponded to F1), a 5 times (p=0.029) increase in mRNA of the fn14 gene and a 2 times (p=0.001) decrease in mRNA of the tweak gene were observed compared with the control point. At the terminal stages of fibrogenesis (the degree of fibrosis F4/F5, the transition of fibrosis to cirrhosis), there was a maximum increase in the level of mRNA of the fn14 gene – about 8 times (p=0.001) compared with the control point. At the same time, at the stage of cirrhosis (F5-F6), the minimum level of mRNA of the tweak gene was observed (20-fold drop, p=0.001) compared to the control point. Conclusions. On the 9th week of the experiment, the transition of fibrosis to cirrhosis was morphologically proved. At this stage, the maximum mRNA level of the fn14 gene was observed, as well as the induction of the tweak mRNA level. A detailed study of the transition point of fibrosis to cirrhosis requires additional attention and further study. Perhaps this point will help reveal new details about the role of the Tweak/Fn14 signaling pathway in the process of chemically induced fibrogenesis. Additional studies are required to obtain even more detailed information, taking into account miRNAs, long non-coding RNAs, and other regulatory elements; epigenetic and metagenomic parameters.

This study aimed to explore the manufacture of high-fat pellets for obesity induction diets in male Wistar rats and determined its effect on lipid profiles and body mass index. It was an experimental laboratory method with a post-test randomized control group. Formulation of high-fat pellets (HFD) and physico-chemical characteristics of pellets were conducted in September 2019. This study used about 28 male Wistar white rats, two months old, and 150-200 g body weight. Rats were acclimatized for seven days, then divided into four groups: 7 rats were given a standard feed of Confeed PARS CP594 (P0), and three groups (P1, P2, P3) were given high-fat feed (HFD FII) 30 g/head/day. The result showed that the mean fat content of Formula II pellets (HFD FII) was higher (25.44% ± 0.16) than Formula I pellet (HFD FI) (22.55% ± 0.16) and standard feed (3%). The mean of body weight and BMI of obesity induction rat groups (P1, P2, P3) were significantly higher than the standard rat group (P0) (p 0.05). Feed consumption in the rat fed with HFD FII pellets was higher than the standard group (P0). It means that rats preferred the HFD FII pellets. The lipid profile of the obesity induction group showed higher total cholesterol, triglycerides, and LDL, while the HDL levels were significantly lower than the standard feed group (P0). LSD post-hoc test results between P1, P2, and P3 showed no difference in the mean lipid profile (p> 0.05). Giving HFD FII pellets, a source of fat from butter, full cream milk powder, and eggs of purebred chickens for eight weeks could make male Wistar rats obese and dyslipidemia

The effect of solvents extracts of G. kola administered to rats at 50, 250 and 500 mg/kg for two weeks was investigated on body weight and serum biochemical parameters using standard analytical-biochemical methods. The extracts at all doses investigated proved that only the 250 mg/kg of the aqueous and methanolroot extracts were able to reduce rat’s body weights. Rats given the methanol extract had no significant differences in the values of AST, total protein, cholesterol, total bilirubin, and urea whereas had significantly increased ALP activity, and albumin content (at all doses used) and direct bilirubin (at 250 mg/ kg), compared to control (p

BackgroundThis study examined the use of solid lipid nanoparticles (SLNs) to administer Dacarbazine (DTIC) to skin melanoma cells with minimal adverse effects. Melanoma is a tricky skin cancer to cure, and standard chemotherapy has many negative effects. Encapsulating DTIC in SLNs may allow the drug to target melanoma cells without harming healthy cells. The study developed and tested DTIC-loaded SLNs for skin melanoma treatment.MethodsThis study encapsulated Dacarbazine (DTIC) in solid lipid nanoparticles (SLNs). SLNs with reversed micelles were produced utilizing specified ratios of the surfactant Kolliphor® P188 and phosphatidylcholine. To track SLN drug localisation, gold nanoparticles were conjugated to the DTIC. Nanoparticle size and form were examined using DLS and TEM. These approaches ensured SLNs had the correct size and shape for drug delivery.Significant findingsIn the study, various parameters of the developed solid lipid nanoparticles (SLNs) were evaluated, including particle size, zeta potential, polydispersity index (PDI), entrapment efficacy, and cumulative drug permeation. The values for these parameters varied across the different formulations, with particle size ranging from 146 ± 4.71 nm to 715 ± 7.36 nm, zeta potential from -12.45 ± 2.78 mV to -30.78 ± 2.83 mV, PDI from 0.17 ± 0.013 to 0.51 ± 0.023, entrapment efficacy from 37.78 ± 2.78% to 87.45 ± 4.78%, and cumulative drug permeation from 117 ± 4.77 μg/cm2 to 275 ± 5.67 μg/cm2. To determine the optimal anti-cancer formulation, the DTIC-SLNs-8 nanoparticles were mixed with an optimized concentration of Gellan gum (0.01% w/v) and applied to DMBA-induced skin tumors in rats for six weeks, twice daily. Histopathology demonstrated that DTIC-SLNs-8-treated rats had less keratosis, inflammatory responses, and angiogenesis than free DTIC-treated rats. The development of SLNs may be a promising approach for melanoma treatment due to their improved drug retention over the skin. The optimised anti-cancer formulation DTIC-SLNs-8 showed improved efficacy with minimal side effects as compared to free DTIC.

Accumulating evidence suggests that maternal overnutrition can result in a higher development risk of obesity and renal disease in the offspring's adulthood. The present study tested different lipid levels in the maternal diet during pregnancy and lactation and its repercussions on the offspring of Wistar rats. Offspring of 1, 7, 30 and 90-d-old were divided into the following groups: Control (CNT) – offspring of dams that consumed a standard chow diet (3.5% of lipids); Experimental 1 (EXP1) – offspring of dams exposed to a high-fat diet (HFD) (28% of lipids); and Experimental 2 (EXP2) – offspring of dams exposed to a HFD (40% of lipids). Regarding maternal data, there was a decrease in the amount of diet ingested by EXP2. Daily caloric intake was higher in EXP1, while protein and carbohydrate intakes were lower in EXP2. While lipid intake was higher in the experimental groups, EXP1 consumed more lipids than EXP2, despite the body weight gain being higher in EXP2. Adult offspring from EXP1 presented higher blood glucose. Regarding morphometric analysis, in both experimental groups, there was an increase in the glomerular tuft and renal corpuscle areas, but an increase in the capsular space area only in EXP1. There was a decrease in the glomerular filtration rate (GFR) in EXP1, in contrast to an increase in GFR of EXP2, along with an increase in urinary protein excretion. In conclusion, the maternal HFDs caused significant kidney damage in offspring, but had different repercussions on the type and magnitude of recorded change. [ABSTRACT FROM AUTHOR]

Background: Urolithiasis is a medical condition that, despite substantial research in the field of urology, has yet to find a cure within the allopathic medical approach. The process of stone development, known as nephrolithiasis, can occur within the kidney or any segment of the urinary tract, encompassing the ureters and bladder. Material and Methods: The seeds of Cassia auriculata (Linn.) were obtained in June 2021 from Mettukadai hamlet, located in the Erode District of Tamilnadu, India. The herbarium of the plant was meticulously assembled, verified, and afterwards deposited as a voucher specimen. The voucher specimen was retained within the college premises for future reference. Results: The current investigation involved conducting a preliminary phytochemical analysis on the ethanolic seed extract of Cassia auriculata Linn. The research revealed the existence of many phytochemical constituents, including Alkaloids, Flavanoids, Carbohydrate, Sterols, Phytosterols, Phenols, Terpenoids, Amino acids, and Anthraquinones. The acute toxicity experiments revealed that rats exhibited tolerance to a maximum dose of 2000 mg/kg body weight, and no discernible alterations in behavior were detected across all experimental groups. Hence, fractions equivalent to one-fourth and one-eighth of the maximum tolerated dose of 200 mg/kg body weight were selected for subsequent investigations. Conclusion: In summary, the findings suggest that the application of an ethanolic seed extract derived from Cassia auriculata Linn effectively decreased the progression of urinary stone formation. Additionally, it appears that the efficacy of the treatment impact surpasses that of its preventative counterpart. [ABSTRACT FROM AUTHOR]

Background: Traditional medicine is gaining traction in Africa. 92.1% of diabetes patients at the University Teaching Hospital in Zambia use herbal medicine. Kigelia africana is a botanical species used in traditional medicine for diabetes due to its phytochemical composition. This study aimed to determine the phytoconstituents, radical scavenging activities, total flavonoid concentration, and total phenolic content of the antidiabetic bioactive Kigelia africana fruit fractions. Methods: Using UV spectrophotometer we determined the total phenolic content (TPC), total flavonoid content (TFC) and free radical scavenging activity. Alloxan-induced diabetes rat models were used to determine the antidiabetic effect in vivo. Phytoconstituent analysis was via gas-chromatography Mass spectrophotometry (GCMS). Results: The ethyl acetate fraction demonstrated superior antidiabetic activity, reducing blood glucose levels from 28.42±2.7 mmol/l to 8.16±4.4 mmol/l. Statistical analysis showed no significant difference between the ethyl acetate fraction and Glibenclamide, (p=0.152). Although the ethyl acetate fraction had a higher reading, there was no statistically significant difference found in Total Phenolic content (TPC) (p=0.3) and Total Flavonoid content (TFC) (p=0.06). IC50 values for DPPH were 0.05330 (chloroform), 0.05352 (ethyl acetate), and 0.4013 (butanol). GC-MS analysis revealed the presence of important fatty acids, methyl furfural, furan carboxylic acid and4-pyran-4-one derivatives. Conclusion: The GC-MS fingerprint of the antidiabetic fractions revealed important fatty acids and phenolic compounds that could be attributed to the observed antidiabetic activity. [ABSTRACT FROM AUTHOR]

The functional characteristics of the thoracic aorta in Wistar rat with experimental arterial hypertension were studied using MRI. The intravital images of the aorta were obtained using a synchronizer of cardiac and respiratory cycles. The pulse-gradient Turbo-spin-echo sequence and the BODY CARDIAC movie 10 mode were used. The unfavorable factor of increased BP initiated structural and functional changes in the thoracic aorta. At the initial stages, they manifested by an increase of the lumen and a decrease in endothelium-dependent vasodilation. Progression of arterial hypertension (3-6 months) was associated with narrowing of the lumen of both ascending and descending parts of the aorta. Deformation of the aortic arch due to increased density of the vascular wall was observed by the sixth month of the development of arterial hypertension. [ABSTRACT FROM AUTHOR]

The study was designed to determine the fluoride distribution after its oral exposure in drinking water and its associated impact on biochemical, antioxidant markers and histology in the liver, kidney, and heart of male Wistar rats. On 100 ppm exposure, the highest accretion of fluoride occurred in the liver followed by the kidney and heart. Fluoride exposure significantly (p˂0.05) increased the plasma levels of dehydrogenase, aminotransferases, kidney injury molecule-1 (KIM-1), and other plasma renal biomarkers but decreased the levels of total plasma proteins and albumin in a dose-dependent manner. Reduction (p˂0.05) in the activities of antioxidant enzymes viz. acetylcholinesterase, arylesterase, superoxide dismutase, catalase, glutathione peroxidase, and reductase with increased levels of protein and lipid peroxidation was recorded in the liver, kidney, and heart of fluoride-administered rats. Fluoride exposure (100 ppm) induced lipid peroxidation was highest in kidney (4.4 times) followed by liver (2.6 times) and heart (2.5 times) and as compared to their respective control. The percent rise in protein oxidation at 30% was almost equal in the kidney and liver but was 21.5% in the heart as compared to control. The histopathological alterations observed included congestion and hemorrhage along with degeneration and necrosis of parenchymal cells in hepato-renal tissues and myocardium, severity of which varied in a dose-dependent manner. Taken together, fluoride distribution in the liver, heart, and kidney after chronic fluoride intake correlated well with fluoride-induced hepatic and cardio-renal toxicity in a concentration-dependent manner. These results draw attention that chronic fluoride intake pose a significant health risk for human and animal residents of fluoride endemic areas. [ABSTRACT FROM AUTHOR]

The variety of stressful conditions in daily human activity requires nutritional support with safe, specialized food products containing functional food ingredients (FFIs) enriched with biologically active plant substances with proven adaptogenic properties. In this in vivo study, by evaluating a set of physiological parameters and biochemical markers, we investigated the effectiveness of the developed FFIs from Chenopodium quinoa grains in stress conditions induced by daily episodes of immobilization for 36 days. The results of the evaluation of the anxiety-like functions, locomotor, and search activity of rats in the "open field" and "elevated plus maze" tests demonstrated the ability of FFIs to reduce stressful behavior induced by immobilization. The improvement in the long-term memory of animals treated with FFIs was noted in the passive avoidance test. Together with the hypolipidemic effect and compensation of transaminase levels, FFIs normalized the excretion of catecholamines in the urine and reduced the levels of malondialdehyde to values of the control group. According to the results of the assessment of FFI acute oral toxicity, the LD50 value exceeded 5000 mg/kg of body weight, which categorizes the FFIs under hazard class 5—substances with low hazard. The conducted experiment demonstrated the effectiveness of nutritional support with FFIs on the selected stress model. The positive safety profile of FFIs makes them reasonable to study on other stress models and to conduct clinical testing as part of specialized food products in various categories of people exposed to chronic stress. [ABSTRACT FROM AUTHOR]

Non-steroidal, anti-inflammatory drugs and statins are two widely prescribed drug classes that affect bone formation. The aim of this study was to elucidate the effect of diclofenac and simvastatin in artificial bone defect healing. One hundred and forty-four male Wistar rats were used, and the specimens were divided into groups, with respect to the route of drug administration and the type of defect healing (with or without collagen membrane), and subgroups, with respect to the study duration (2, 4 or 8 weeks). Diclofenac was intramuscularly administered while simvastatin was administered both systemically and locally. Animals were euthanized and specimens were histomorphometrically analyzed to evaluate the percentage of new bone formation (%). Bone healing that occurred without any intervention developed more steadily than that of all other groups. Diclofenac exerted a clear, direct inhibitory effect on bone healing and its systemic administration should be avoided. The systemic administration of simvastatin was related to severe myopathy, while the solvent for the local administration of simvastatin seemed to play significant role in bone growth, as simvastatin, when it is administered intraperitoneally in a DMSO solution, appeared to promote bone healing. Local administration may have a significant impact on bone healing and it should be further investigated with the type of solvent or carrier that is used, which both may play a significant role in bone repair induction. [ABSTRACT FROM AUTHOR]

The Himatanthus genus presents anti-inflammatory, antioxidant activities, suggesting potential wound-healing properties. This study aimed to develop and analyze the wound-healing properties of a photopolymerizable gelatin-based hydrogel (GelMA) containing an ethanolic extract of Himatanthus bracteatus in a murine model. The extract was obtained under high pressure conditions, incorporated (2%) into the GelMA (GelMA-HB), and physically characterized. The anti-inflammatory activity of the extract was assessed using a carrageenan-induced pleurisy model and the GelMA-HB scarring properties in a wound-healing assay. The extract reduced IL-1β and TNF-α levels (48.5 ± 6.7 and 64.1 ± 4.9 pg/mL) compared to the vehicle (94.4 ± 2.3 pg/mL and 106.3 ± 5.7 pg/mL; p < 0.001). GelMA-HB depicted significantly lower swelling and increased resistance to mechanical compression compared to GelMA (p < 0.05). GelMA-HB accelerated wound closure over the time course of the experiment (p < 0.05) and promoted a significantly greater peak of myofibroblast differentiation (36.1 ± 6.6 cells) and microvascular density (23.1 ± 0.7 microvessels) on day 7 in comparison to GelMA (31.9 ± 5.3 cells and 20.2 ± 0.6 microvessels) and the control (25.8 ± 4.6 cells and 17.5 ± 0.5 microvessels) (p < 0.05). In conclusion, GelMA-HB improved wound healing in rodents, probably by modulating the inflammatory response and myofibroblastic and microvascular differentiation. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a diabetes mellitus (DM) complication that causes visual acuity impairment and loss of sight in the working population, mainly in developed countries. According to the WHO, DR accounts for 5% of the world's 37 million blind people. The prevalence of diabetic retinopathy was highest in Africa, followed by North America and the Caribbean and South and Central America. Hyperglycemia can generate excessive ROS that activates multiple pathways, which can damage the cells. Oxidative stress and inflammatory process are intricate in the DR pathological mechanism. Bilobalide is the main bioactive compound isolated from the Ginkgo biloba, a plant utilized in folklore medicine. Bilobalide, a sesquiterpene trilactone, exhibits excellent antioxidant activity. But the molecular mechanisms associated with such effects, especially the antioxidant-related mechanism, have not been documented. Hence, this investigation explored whether bilobalide may attenuate DR in streptozotocin (STZ)-prompted diabetic rats. The effects of bilobalide on parameters of antioxidant content, oxidative stress, and inflammatory factors in the retinal tissues were evaluated by ELISA, RT-PCR, and immunohistochemistry methods. Bilobalide improved caloric management by reducing food consumption and increasing body weight. Furthermore, the administration of bilobalide decreases the blood glucose level and glycosylated (HbA1c) hemoglobin. The anti-retinopathy activity of bilobalide was established by the increase in the total retina thickness (TRT), inner nuclear layer (INL), and outer nuclear layer (ONL) in diabetic rats. Additionally, the serum level of MDA was decreased. In contrast, the antioxidant enzyme (SOD and CAT) levels were increased with TAC plus lower Keap1 and higher Nrf2 expression in the retina when associated with the DM rats. Moreover, bilobalide increased the nuclear factor erythroid 2-related factor 2 (Nrf2) and Heme oxygenase-1 (HO-1) expression level and inflammatory mediators (NF-κβ p65, TNF-α, IL-1β, and VEGF), thus inhibiting oxidative stress. Bilobalide can be effective against DR, and the possible mechanism may be relatively elucidated by decreasing oxidative stress and anti-inflammatory activities. But the further investigation should be directed to expose the precise mechanism. [ABSTRACT FROM AUTHOR]

Waltheria indica Linn. root (WILR) is a multipurpose medicinal plant with abundance of phytochemical compounds. The optimal solvents for extraction of a particular bioactive compound depends not only on the yield of the compound but also on the toxic effect of the solvent used. Therefore, this study was designed to evaluate the toxic effects of hexane, dichloromethane and ethyl acetate solvent fractions of WILR in male Wistar rats. Three doses (200, 500, or 1000 µg/kg BW) of hexane, dichlorometh ane and ethyl acetate solvent fractions of WILR were used. Male Wistar rats (n=5) were administered with 200, 500, or 1000 µg/kg of hexane, dichloromethane, and ethyl acetate soluble extracts of WILR, while control received distilled water, daily for 15 days. The rats were thereafter sacrificed, blood samples were collected and serum separated. Haematological serum biochemical parameters were determined according to standard procedure. The result showed nonsignificant effect on relative organ weight and haematological parameters while the serum ALT was significantly increased by administration of hexane, dichloromethane, and ethyl acetate soluble extracts of WILR. Blood Urea Nitrogen was also increased significantly (p < 0.05) at 200 and 500 µg/kg of hexane and dichloromethane respectively. The ethyl acetate and hexane fraction also caused severe periportal cellular infiltration in the liver while the hexane fraction caused glomerular necrosis. The hexane, dichloromethane and ethyl acetate soluble extracts of (WILR) have adverse effect on the integrity liver and kidney. Hence, these extracts should be used with caution in patient with hepatic and renal impairment. [ABSTRACT FROM AUTHOR]

This study compared different conditions to establish a rat model of denture stomatitis. Immunocompetent Wistar rats were divided into two groups (n  = 35): Tetracycline = administration of 0.83 mg/ml of tetracycline hydrochloride 7 days before induction of denture stomatitis and amoxicillin = administration of 0.156 mg/ml of amoxicillin with clavulanic acid 4 days before induction of denture stomatitis. A suspension of Candida albicans was inoculated on the palate followed by the use of a palatal device contaminated with C. albicans inoculum for 4 days to induce denture stomatitis. As controls, some rats were not submitted to any procedure or used a sterile palatal device for 4 days. The development of denture stomatitis was confirmed by visual analysis, colony-forming units per milliliter (CFU/ml) count, histopathological and immunohistochemical analyses, and through myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) assays. Rats were euthanized right after device removal (T0), 4 (T4), or 6 (T6) days after device removal. Tetracycline improved the development of the disease, with more severe clinical signs at T0. Similar results were observed in the CFU/ml count and in the histometric and immunohistochemical analyses. Higher MPO expression was detected in the palates of the tetracycline group (P  = .006). Despite the subtle differences between antibiotics, tetracycline showed better results in inducing and maintaining denture stomatitis for at least 4 days after device removal. [ABSTRACT FROM AUTHOR]