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Panax ginseng is commonly used in Chinese medicine and Western herbal preparations. However, it has also been recently noted to be associated with some cardiac pathologies-including cardiogenic shock due to acute anterior myocardial infarction, trans-ischemic attack, and stent thrombosis. This study was aimed to elucidate acute and subacute effects of the low and high doses of standardized Panax ginseng extract (sPGe) on cardiac functions. Rats were randomly assigned to control group, acute low-dose group (ALD), subacute low-dose group (SALD), acute high-dose group (AHD), and subacute high-dose group (SAHD). The cardiac effects of sPGe were evaluated using hemodynamic, biochemical, echocardiographic, genetic, and immunohistopathologic parameters. Mean blood pressures were significantly lower in all sPGe-treated groups compared with the control group. Troponin I and myoglobin levels were increased in the SALD, AHD, and SAHD groups. Mitral E-wave velocity was reduced after sPGe administration in all the groups. Acidophilic cytoplasm and pyknotic nucleus in myocardial fibers were observed in AHD and SAHD groups. Cu/Zn-SOD1 gene expressions were significantly higher in the sPGe-treated groups whereas caveolin 1 and VEGF-A gene expressions were not changed. According to our results, sPGe may have a potential effect to cause cardiac damage including diastolic dysfunction, heart failure with preserved ejection fraction, and reduction of blood pressure depending on the dose and duration of usage. Healthcare professionals must be aware of adverse reactions stemming from the supplementation use, particularly with cardiac symptoms.

Alzheimer's disease (AD) is a progressive neurodegenerative disease. This study was performed to determine the possible relationship between melatonin, which is known to play a role in the neuro-protective mechanism in AD, and fasciculation and elongation protein zeta 1 (FEZ1). Thirty male rats were included and separated into 3 groups (n = 10) as vehicle (artificial cerebrospinal fluid), streptozotocin (STZ) and STZ+melatonin (MLT). Two intracerebroventricular (icv) injections of 3 mg/kg STZ were made 48 hours apart. MLT injections were implemented for 14 days (ip; 10mg/kg/day). The Morris Water Maze (MWM) test was performed and rats were sacrificed to assess FEZ1 gene expression and protein levels from the hippocampus tissues and serum levels of noradrenaline (NA), dopamine and serotonin were determined from the blood samples. It was determined that the FEZ1/β-actin protein ratio in the STZ group was significantly higher than that of the Vehicle group (p < 0.05) and in the MLT‑administered group, the protein levels were decreased to the levels observed in the Vehicle group. Serum NA levels of STZ and STZ+MLT groups were found to be lower than those in the Vehicle group, while no difference was found regarding dopamine and serotonin levels. These findings show that reversal of increased FEZ1 levels in AD-induced rats with melatonin administration is the evidence of the effect of melatonin through FEZ1 in AD (Tab. 2, Fig. 5, Ref. 67). Keywords: FEZ1, Alzheimer's disease, melatonin, rat, microtubules, mitochondria.

We investigated the effects of acrylamide (AA) and vitamin E treatment during pregnancy on brain tissues of fetuses and on adult rats. Pregnant rats were divided into five groups: control, corn oil, vitamin E, AA, vitamin E +AA. The rats administered AA received10 mg/kg/day and those administered vitamin E received 100 mg/kg/day both by via oral gavage for 20 days. On day 20 of pregnancy, half of the pregnant rats were removed by cesarean section in each group. Morphological development parameters were measured in each fetus and histopathological, biochemical and genetic analyses were conducted on the fetuses. The remaining pregnant rats in each group gave birth to the fetuses vaginally and biochemical, histopathological, genetic and cognitive function tests were conducted when the pups were 8 weeks old. AA administration caused adverse effects on fetus number, fetal weight, crown-rump length, placenta and brain weight. AA negatively affected malondialdehyde, reduced glutathione, total oxidant and antioxidant status, brain derived neurotrophic factor (BDNF) levels, brain tissue morphology, histopathology error score and gene expression (BDNF/β-actin mRNA ratio) in fetuses. AA administration caused disruption of biochemical, histopathological and cognitive functions in adult rats. Vitamin E provided protection against neurotoxicity in both fetuses and adult rats. We conclude that exposure to AA during pregnancy should be avoided and adequate amounts of antioxidants, such as vitamin E, should be consumed.

Scope: We investigated the potential beneficial effect of Apocynin (APO) on motor and cognitive functions in experimental Alzheimer’s disease (AD). Materials and Methods: Experimental AD was induced in rats by intraventricular streptozotocin (STZ) injection. Sham group received artificial cerebrospinal fluid (CSF). Both groups were randomly divided into two subgroups. One of the subgroups received intraperitoneal APO for while the other had normal saline (NS). The animals were evaluated with rotarod, accelerod and Water-Maze tests before and after the treatment. Additionally, biochemical markers of oxidative stress such as malondialdehyde (MDA) and reduced glutathione (GSH) were analyzed from brain specimens. Standard histological evaluation and transmission electron microscopy (TEM) were used to evaluate the neural damage. Results: The difference between STZ+NS in comparison with CSF+NS, CSF+APO and STZ+APO were statistically significant on 30 and 40 rpm on rotarod test. GSH levels, accelerod and Water-Maze test results were not statistically significant between subgroups. However, MDA differences between STZ+NS in comparison with CSF+NS, CSF+APO and STZ+APO were statistically significant. Hemotoxilene eozine staining and TEM results showed apocynins protective effect. Conclusion: These results indicate that APO can provide neuro-protective effect for motor but not for cognitive performance in experimental AD. Keywords: Alzheimer’s disease, Streptozotocin, Apocynin, Rotarod test, Accelerod test, Water-Maze test

The aim of this study was to evaluate the impact of intracerebroventricular chronic fibroblast growth factor 21 (FGF21) infusion on hypothalamic–pituitary–thyroid (HPT) axis, energy metabolism, food intake and body weight. Thirty male Wistar albino rats were used and divided into three groups including control, sham (vehicle) and FGF21 infused groups (n = 10). Intracerebroventricularly, FGF21 and vehicle groups were infused for 7 days with FGF21 (0.72 µg/day) and artificial cerebrospinal fluid, respectively. During the experimental period, changes in food intake and body weight were recorded daily. Serum thyroid stimulating hormone (TSH), Triiodothyronine (T3) and thyroxine (T4) levels were measured using ELISA. TRH and uncoupling protein 1 (UCP1) gene expressions were analyzed by using RT-PCR in hypothalamus and adipose tissues, respectively. Chronic infusion of FGF21 significantly increased serum TSH (p

Apelin, a ligand for G protein-coupled APJ receptor, is a peptide hormone. Although apelin and APJ receptors are determined in hypothalamus and thyroid gland its role in the hypothalamus–pituitary–thyroid (HPT) axis and mechanism of action on energy metabolism is not clear. This suggests that apelin may play a role in the HPT axis and energy metabolism. This study was designed to determine possible effects of centrally administered apelin-13 on the HPT axis and energy metabolism. A total of 40 adult male Sprague Dawley rats were divided into four groups (n = 10 each group). Intact rats served as control group while the sham group received vehicle of apelin. Apelin-13 was injected intracerebroventricularly at the doses of 1 and 10 nmol, for 7 days in the rats in the experimental group. At the end of the experimental protocol, animals were decapitated and brain, blood, white and brown adipose tissues samples were collected. There was no significant difference between the groups in terms of hypothalamic TRH mRNA levels. Serum TSH levels were significantly higher in all groups compared to the control group (p

In this study, gene expression profile of caveoline and the kidney MDA levels and serum BUN and creatinine levels were investigated in experimentally induced renal failure case of rats. In the experimental group, rats were injected with 30 mg/kg of cyclosporin A via subcutaneous route for 28 days. In the control group, rats were injected with cremophor EL, vehicle for cyclosporin A, for 28 days. Caveolin gene analysis and MDA analysis in the kidney tissue as well as serum BUN and creatinine analysis were performed at the end of the experiment. Caveolin gene expression of experimental group was significantly reduced (P < 0.05), while the MDA level was significantly increased compared to those of control (P < 0.05). Serum BUN and creatinine levels were significantly increased in the experimental group compared to the control group (P < 0.05). In the Cyclosporin A induced chronic renal failure model, we suggest that the induction of the Cav-1 gene expression may prevent the renal tissue damage. [Med-Science 2017; 6(3.000): 401-5]

Cecal ligation and puncture (CLP) is a commonly used model of sepsis in vivo. We investigated the effects of dexpanthenol (DXP) on heart, lung and aorta in CLP-induced sepsis in rats. Rats were divided into four groups of eight: group 1, sham (SH); group 2 (DXP), 500 mg/kg DXP injected intraperitoneally (i.p.); group 3 (CLP), CLP performed; group 4 (CLP + DXP), 500 mg/kg DXP injected i.p. after CLP. Heart, lung and aorta specimens were harvested for histopathological and biochemical analysis. Heart rate increased in group 3 compared to group 1; DXP administration to group 4 did not alleviate this change. In heart tissue samples, MDA levels were decreased significantly in groups 2 and 4 compared to group 3. The levels of GSH in groups 2 and 3 were elevated compared to groups 1 and 2. SOD activity was increased significantly in group 4 compared to group 3. CAT activity for group 4 was increased significantly compared to groups 1 and 3. We found that caspase-9 and caspase-3 activity was increased after application of CLP. Also, DXP treatment decreased the number of caspase-positive cells significantly compared to group 3. DXP appears to be promising for reducing sepsis-related mortality.

Irisin is a product of fibronectin type III domain-containing protein 5 (FNDC5) and plays an important role in energy homeostasis. In this study, we aimed to determine effects of intracerebroventricular administration of irisin on the hypothalamus-pituitary-gonadal axis by molecular, biochemical, and morphological findings. Fourty male Wistar-Albino rats were used and divided into four groups including control, sham (vehicle), 10, and 100 nM irisin infused groups (n = 10). Hypothalamic gonadotropin releasing hormone (GnRH) level and serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were determined. Testicular tissue histology and spermiogram analysis were also performed. Both irisin concentrations significantly reduced hypothalamic GnRH messenger RNA (mRNA) and protein levels (p < 0.05). It was found that serum LH, FSH, and testosterone levels and Sertoli and Leydig cell numbers were decreased by irisin administration (p < 0.05). In addition, irisin administration reduced sperm density and mobility (p < 0.05). However, it did not cause any change in testicular and epididymis weights and tubular diameter. Our results reveal that irisin can play a role in the central regulation of reproductive behavior and also reduces testosterone levels by suppressing LH and FSH secretion. These results suggest that the discovery of irisin receptor antagonists may be beneficial in the treatment of infertility.

Irisin, which is secreted from the skeletal muscle in response to physical exercise and defined as a thermogenic peptide, may play an important role in energy metabolism. Thyroid hormones, which are one of the other influential factors on the metabolic status, increase heat production and are the main regulators of energy metabolism. This study was conducted to determine the possible effects of irisin administration on thyroid hormones. Forty adult male Wistar albino rats were used in the study. The rats were equally divided into 4 groups (n = 10). The brain infusion kit was implanted in the groups, and irisin (or solvent as control) was centrally administered to the rats via osmotic mini pumps for 7 days. During the experiment, food consumption, body weights, and body temperatures of the animals were recorded. Food intake was significantly increased in the groups treated with irisin (p 0.05), but their body weights were not changed. Hypothalamic TRH gene expression, serum TSH, fT3, and fT4 levels were significantly lower in the groups treated with irisin as compared to the naive and control groups (p 0.05). In addition, irisin increased UCP1 mRNA expression in white and brown adipose tissue and UCP3 mRNA expression in muscle tissue in rats and also raised their body temperature (p 0.05). Consequently, although central irisin administration has inhibitory effects on the hypothalamic-pituitary-thyroid axis, it seems to be an important agent in the regulation of food intake and energy metabolism.

Irisin, a novel exercise-induced myokine, has attracted attention with its effects on energy metabolism. This study was conducted to determine the possible effects of irisin on nutritional behaviour. In this study, 40 male Wistar Albino rats were separated into 4 groups (n=10 for each group). Osmotic mini-pumps were connected to metal cannulas implanted to lateral ventricle; and artificial cerebrospinal fluid (vehicle), and 10 and 100nM of irisin was infused for 7days. The daily food and water consumptions and body weights of rats were followed up. After the infusion, the animals were killed, and the hypothalamus and blood samples were collected. NPY, POMC, and UCP2 mRNA levels in the hypothalamus were examined by RT-PCR. In serum, leptin and ghrelin levels as well as the levels of metabolic parameters were measured by using ELISA. It was determined that irisin administration increased the daily food consumption (p0.05), without causing significant changes in water consumption and body weight. Irisin also caused increases in ghrelin level in circulation and NPY and UCP2 mRNA levels in the hypothalamus, whereas it decreased the leptin level in circulation and POMC mRNA levels in the hypothalamus (p0.05). Otherwise, irisin caused decrease in LDL, triglycerides and cholesterol levels, while increasing HDL and glucose levels (p0.05). Results indicates that long-term irisin treatment increases food intake without increasing body weight associated with increased ghrelin, NPY and UCP2 mRNAs, and decreased leptin and POMC mRNA in the hypothalamus.

Pancarcı, Şükrü Metin (Balikesir Author), The objectives were to investigate relationships among concentrations of nitric oxide (NO), estradiol 17 beta (E2), and progesterone (P4) in follicular fluids (FF), and quality of cumulus oocyte complexes (COCs) with respect to perifollicular blood flow (FBF). In Experiment I. follicles (138) were classified according to the presence or absence of FBF (assessed with transvaginal Doppler ultrasonography) and diameter of follicles (small, 2-4 mm; medium, 5-8 mm; and large, >= 9 mm). Concentrations of NO in FF did not differ significantly among these size categories. However, NO concentrations in FF with FBF (54.4 +/- 7.4 mu mol/l) were higher (P < 0.05) than in those without FBF (36.6 +/- 4.1 mu mol/l). There was a positive correlation (r = 0.30, P < 0.05) between NO concentrations and the E2:P4 in FF. Rate of E2 active (E2:P4 >= 1) follicles were numerically 1.2(0.8-1.8) times higher in follicles with FBF (38.1%) compared to those without FBF (25.0%). Moreover, rates of E2 active follicles were 6.1 (0.7-55.2) and 1.3 (0.1-17.3) times higher (P < 0.06) in large (43.3%) and medium (14.3%) compared to small follicles (11.1%), respectively. In Experiment II, quality of COCs from 2 to 8 mm follicles, obtained by transvaginal ovum pick up (OPU), was investigated with respect to FBF. Odds ratio to obtain higher quality COCs from follicles with FBF (47.1%) was 3.3 (1.1-9.6) fold higher (P < 0.05) compared to those from follicles without FBF (14.6%). In conclusion, E2:P4, and NO concentrations in FF, as well as FBF, could be used to determine the functionality of ovarian follicles in cows. Moreover, determination of FBF could be useful to predict quality of COCs in cattle. (C) 2012 Elsevier B.V. All rights reserved., TUBITAK (The Scientific and Technical Research Council of Turkey) TUBITAK-TOVAG 106O544

Two experiments were conducted to test the hypothesis that there are dynamic changes in follicular blood flow during follicular deviation and that nitric oxide (NO) in follicular fluid (FF) plays a role in regulation of follicular blood flow. In Experiment I, follicular blood flow of the two largest follicles was monitored by using Power Doppler ultrasonography during follicular deviation in sixteen follicular waves during eight estrous cycles in eight cows. Blood flow did not differ (P0.05) between the dominant follicle (DF) and the largest subordinate follicle (SF) until the beginning of the deviation of the follicular size, but was higher (P0.05) in DF than in the largest SF one and two days after the beginning of diameter deviation in ovulatory (n=5) and atretic (n=11) waves; respectively. In Experiment II, FF was aspirated from DF and the largest SF on the day of diameter deviation (DF, n=6; SF, n=6) and two days later (DF, n=12; SF, n=9). Nitric oxide did not differ (P0.05) between DF and the largest SF on the day of diameter deviation but, one or two days after observed diameter deviation NO concentrations were lower (P0.01) in DF compared to the largest SF. On the day of diameter deviation and two days later E2 levels in FF were higher (P0.01) in DF than in the largest SF. P4 concentrations in FF were higher (P0.05) in DF than in the largest SF on the day of diameter deviation, but did not (P0.05) differ two days later. E2/P4 ratio in FF was the same (P0.05) in DF and the largest SF on the day of diameter deviation, but was higher (P0.01) in DF than in the largest SF one or two days later. In conclusion, area of follicular blood flow of DF and the largest SF increased in parallel with follicular size during follicular deviation. Furthermore, there were relationships between changes in follicular blood flow, NO concentrations and E2/P4 ratio in FF following the beginning of diameter deviation in cattle.

Objective To investigate protective effects of Marrubium cordatum extract on ovary torsion–detorsion. Design Controlled research study. Setting Marrubium cordatum extract was obtained by methanol extraction. Animal(s) Six-month-old female New Zealand rabbits. Intervention(s) In the first phase, antioxidant activity of M. cordatum extract was evaluated. In the second phase, M. cordatum extract at doses of 0, 250, 500, and 1,000 mg/kg was studied for dose determination. In the third phase, the protective role of M. cordatum on ovarian torsion–detorsion injury was evaluated in sham control, torsion–detorsion, torsion–detorsion + M. cordatum (1,000 mg/kg). Main Outcome Measure(s) 1,1-Diphenyl-2-picrylhydrazyl, nitric oxide radical scavenging activity, reducing power capacity, and total phenolic compounds were assayed. Glutathione, malondialdehyde, catalase, and glutathione peroxidase were measured. Histopathological examination was also conducted. Result(s) Marrubium cordatum significantly inhibited 1,1-diphenyl-2-picrylhydrazyl, nitric oxide radicals, and showed a powerful reducing activity. Marrubium cordatum did not adversely affect biochemical and histopathological parameters at all doses. Malondialdehyde level and catalase activity in the torsion–detorsion group were significantly increased compared with those of the sham group, whereas the glutathione level and glutathione peroxidase activity were significantly decreased compared with those of the sham group. Marrubium cordatum treatment significantly lowered the malondialdehyde level and catalase activity but increased the glutathione level in torsion–detorsion injury. Histopathologically, severe congestion, hemorrhage, edema, and leukocyte infiltration were observed in the torsion–detorsion group. Marrubium cordatum treatment ameliorated these alterations. Conclusion(s) Marrubium cordatum attenuates ischemia–reperfusion-induced biochemical and histopathological alterations.

1. The purpose of this study was to investigate the protective effect of alpha-lipoic acid (LA) on aflatoxin (AF) toxicosis in chicks. 2. Groups of 10 Ross PM3 chicks were given, for 21 d, no AF (C), 60 mg/kg/bwt of alpha-lipoic acid (LA), 150 ppb of aflatoxin (AF1), 150 ppb of aflatoxin plus 60 mg/kg/bwt of alpha-lipoic acid (AF1 + LA), 300 ppb of aflatoxin (AF2), and 300 ppb of aflatoxin plus 60 mg/kg/bwt of alpha-lipoic acid (AF2 + LA). Before the animals were killed, blood samples were drawn for haematological analysis, and then tissue samples were collected for histopathological investigation. Immunohistochemical staining was performed against inducible nitric oxide synthase (iNOS) and nitrotyrosine on liver samples. Apoptotic cell death in liver was assessed by in situ TUNEL assay. The malondialdehyde (MDA) and reduced glutathione (GSH) concentrations in liver and kidney were also determined. 3. Hydropic degeneration and occasional necrosis, bile duct hyperplasia and periportal fibrosis were observed in the livers of AF-treated groups. The severity of these changes was reduced in LA-supplemented AF groups. Occasionally, thymic cortical atrophy, lymphoid depletion in spleen and bursa of Fabricius, and degeneration in the kidney tubule epitheliums were detected in AF groups. The severity of these degenerative changes was slightly reduced in LA supplemented groups. 4. There was moderate to strong iNOS and nitrotyrosine immunoreactivity in the livers of AF groups, while decreased immunoreactivity was observed against both antibodies in the LA supplemented groups. Apoptotic cells were numerous in the AF groups, while greatly reduced in LA supplemented groups. 5. In the liver and kidney of AF-treated groups given 300 ppb of aflatoxin, MDA concentrations were increased as GSH decreased, compared to the control group. LA supplementation of AF-treated birds improved the results compared to the AF only groups, however a statistical difference was observed only in liver tissues between AF2 + LA and AF2 groups. Haematological variables showed no differences among the groups. 6. In conclusion, supplementation of feed with the antioxidant LA, might ameliorate the degenerative effects caused by aflatoxin due to lipid peroxidation.

In this study, Wistar rats were experimentally induced diabetes and the gene expression profile of CuZn-SOD and CAT enzymes were investigated in the liver tissue of these rats. The rats were divided into two groups as control and the experimental diabetes group (DM). In group DM, as a single dose of 50 mg/kg streptozotocin (STZ) dissolved in 0.01 M citrate buffer (pH: 4.5) was given intraperitoneally to the rats. 0.01 M citrate buffer which is the vehicle for STZ was applied to the rats in control group. 72 hours after STZ treatment, blood samples were collected from the tail vein, and the blood sugar levels were measured. Rats with fasting blood sugar levels above 350 mg/dl were considered to be diabetic. The rats were decapitated 21 days after STZ treatment. The liver tissues were collected, and the gene expression profile of CuZn-SOD and CAT in the liver was measured using real-time PCR technique. In conclusion, it was found that a significant decrease was observed in the expression of CuZn-SOD and CAT genes in DM group when they were compared to that of control group. Keywords: Rat, diabetes, streptozotocin, CuZn-SOD, CAT

Objective: The aim of the present study is to evaluate the effect of crocin on mRNA expression of antioxidant enzymes, SOD, CAT and GPX in the brain of the STZ induced diabetic rats.Methods: Thirty animals randomized in three groups containing ten animals in each group as follows; control (non-diabetic rats), DM (STZ-induced untreated diabetic rats), DM+crocin (STZ-induced diabetic rats treated with crocin,). Crocin was given at a dose of 20 mg/kg bw/day by gavage for 21 days.Results: STZ injection caused a significant increase in mRNA expression of antioxidant enzymes, SOD, CAT and GPX when compared to control group. Crocin given to diabetic rats significantly decreased mRNA expression of antioxidant enzymes, SOD, CAT and GPX when compared to DM group.Conclusion: The present study demonstrates that crocin can modulate mRNA expression of antioxidant enzymes, SOD, CAT and GPX and oxidative stress in the brain of the STZ induced diabetic rats.

To investigate if resveratrol can prevent sodium selenite-induced experimental cataract model in rats.Forty-eight Spraque-Dawley rat pups were divided into 3 treatment groups: (1) normal saline-% 5 ethanol injected i.p. on postpatum day 10; (2) Na selenite (30 nmol/g body wt) injected s.c on day 10; (3) Na selenite s.c on day 10+resveratrol (40 mg/kg) i.p on days 10-13. On day 21, cataract development was graded by slit-lamp examination and photography. Encapsulated lenses and erythrocytes were analyzed for reduced glutathione (GSH) and malondialdehyde (MDA), a marker of lipid peroxidation. Lenses were also analyzed for total nitrite (TN).All control lenses in group 1 were clear. In group 2, all rats developed cataracts (grade 3-grade 6), whereas in group 3, only 9 of 16 rats developed cataracts (grade 2-grade 3). The difference of cataract frequency between groups 2 and 3 was statistically significant (p0.05). Group 3 lenses and erythrocytes had higher mean GSH and lower mean MDA levels than those in group 2 (p0.05). TN was highest in group 3 and lowest in group 1 (p0.05).Resveratrol suppressed selenite-induced oxidative stress and cataract formation in rats. This protective effect was supported by higher GSH and lower MDA in lens and erythrocytes. The presence of oxidative stress in selenite cataract development and its prevention by resveratrol support the possibility that high natural consumption of resveratrol in food can help prevent human senile cataract.

This experimental study was designed to determine the changes in tissue levels of malondialdehyde, end-product of lipid peroxidation (MDA), reduced glutathione (GSH) and xanthine oxidase (XO) and the effect of caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE) on these metabolite levels after adnexal torsion-detorsion model in rats.Forty adult female albino rats were divided into five groups: basal control (n = 8), sham operation (n = 8), torsion-detorsion plus saline (n = 8), torsion-detorsion plus CAPE (n = 8). and only torsion (n = 8). Rats in the sham operation group underwent a surgical procedure similar to the other groups but the adnexa was not torsioned. Rats in the torsion group were killed after 360 degrees clockwise adnexal torsion for 3 h and ovaries were harvested. CAPE was injected intraperitoneally 30 min before detorsion in the CAPE/detorsion group and saline was administered in the saline/detorsion group. After 3 h of adnexal detorsion, the rats in both groups were killed and adnexa were surgically removed.MDA levels and XO activities in torsion-detorsion plus saline group increased significantly when compared to basal control, torsion and sham operation groups (P0.001). In the CAPE group, MDA levels and XO activities were lower than those of torsion-detorsion plus saline group, and differences between the two groups were statistically significant (P0.001). GSH levels in torsion-detorsion plus saline group were decreased significantly when compared to basal control and sham operation groups (P0.001). GSH levels in the CAPE group were higher than those of torsion-detorsion plus saline group, and differences between the two groups were statistically significant (P0.004). Morphologically, polymorphonuclear leukocytic infiltration and vascular dilatation were obvious in the ischemia-reperfusion damaged ovary, a change partially reversed by CAPE.These results suggest that administration of CAPE has beneficial effects in the prevention of ischemia-reperfusion injury of the ovaries.

This experimental study was designed to determine the effects of melatonin on the levels of malondialdehyde (MDA), reduced glutathione (GSH), xanthine oxidase (XO) after adnexial torsion/detorsion (ischemia/reperfusion, I/R) of the ovaries of in rats. Forty adult albino rats were divided into five groups: sham operation, torsion, I/R plus saline, I/R plus melatonin and torsion plus melatonin. Rats in the sham-operated group underwent a surgical procedure similar to the other groups but the adnexa was not occluded. Rats in the torsion group were killed after adnexal torsion for 3 hr. Melatonin and saline were injected intraperitoneally (10 mg/kg) 30 min before detorsion to the I/R plus melatonin group and I/R plus saline group respectively. After 3 hr of ovarian detorsion, the rats were killed and ovaries were removed. Melatonin was injected intraperitoneally (10 mg/kg) 30 min before torsion to the torsion plus melatonin group. After 3 hr of ovarian torsion, the rats were killed and ovaries were harvested. The tissue levels of MDA, GSH and XO were measured. MDA and XO levels in the I/R plus saline group increased significantly when compared with torsion and sham-operated groups (P < 0.001). MDA and XO levels in the I/R plus melatonin group were lower than I/R plus saline and differences between the two groups were statistically significant (P < 0.001). GSH levels in the I/R plus saline group decreased significantly when compared with ischemia and sham-operated groups (P < 0.001). GSH levels in the I/R plus melatonin treated rats were significantly higher than I/R plus saline and ischemia groups (P < 0.001). The tissue levels of XO, MDA and GSH were similar between ischemia and ischemia plus melatonin groups. Morphologically, polymorphonuclear neutrophil infiltration and vascular dilatation were obvious in the I/R-damaged ovaries, and the changes also partially reversed by melatonin. This study demonstrates that melatonin protects the ovaries against oxidative damage associated with reperfusion following an ischemic insult.

Objective: The aim of this study is to investigate the effects of resveratrol on histopathological changes, antioxidant status and lipid peroxidation, in torsion-detorsion injury in rat ovaries. Method: To determine whether ischemia followed by reperfusion can induce ovarian oxidative damage, we created a model of adnexal ischemia-reperfusion by using rats. Ischemia was induced by unilateral occlusion of the tubo-ovarian vessels for 3 h. Reperfusion was achieved by releasing the occlusion and restoring the circulation for 3 h. Thirty-two adult female albino rats were divided equally into 4 groups: sham operation, torsion, saline/detorsion and resveratrol/detorsion. Rats in the torsion group were killed after 360° clockwise adnexal torsion for 3 h. Resveratrol was injected intraperitoneally 30 min before detorsion in the resveratrol/detorsion group, and saline was administered in the saline/detorsion group. After 3 h of adnexal detorsion in both of these groups, the rats were killed and adnexa were removed. The tissue levels of malondialdehyde, reduced glutathione and xanthine oxidase activity were measured. Results: Malondialdehyde and xanthine oxidase levels in the saline/detorsion group were increased significantly when compared to the torsion and sham operation groups (p < 0.001). Malondialdehyde levels in the resveratrol group were lower than in the saline/detorsion group, and differences between the two groups were statistically significant (p < 0.001). Xanthine oxidase levels in the resveratrol group were lower than in the saline/detorsion and torsion groups, and differences between these groups were statistically significant (p < 0.001). Reduced glutathione levels in the saline/detorsion group were decreased significantly when compared to the torsion and sham operation groups. Reduced glutathione levels in the resveratrol group were significantly higher than in the saline/detorsion group (p < 0.006). Histological examination showed a significant improvement in ovarian morphology in the resveratrol-treated rats compared with the ischemia and ischemia-reperfusion groups. Conclusion: Our results demonstrated that intraperitoneal resveratrol administration reduced the lipid peroxidation products of ischemic rats and ovarian damage was reduced as indicated by histological examination.

It is well established that some agents such as aminoglycosides generate free oxygen radicals, leading to an increased oxireductase production, which in turn increases tissue toxicity. The aim of this study is to test whether melatonin, the chief secretory product of the pineal gland and a highly effective antioxidant and free radical scavenger, reduces the nephrotoxicity caused by amikacin (AK). Herein, we investigated the physiologic and pharmacological role of melatonin in influencing AK-induced nephrotoxicity. For this, pinealectomized (Px) and sham operated (non-Px) rats were used. Both AK and melatonin were administered to all groups. We investigated the effects of melatonin on AK-induced changes in levels of malondialdehyde (MDA), a lipid peroxidation product, glutathione (GSH), an antioxidant whose levels are influenced by oxidative stress, and blood urea nitrogen (BUN) and serum creatine (Cr) levels. Morphologic changes in the kidney were also examined by using light microscopy. MDA levels were found to be higher in Px than in non-Px AK-treated animals. Melatonin administration to Px rats reduced MDA levels. In relative to non-Px rats, Px animals treated with AK had significantly lower GSH concentrations while melatonin administration elevated GSH levels in the kidney; however, this stimulatory effect of melatonin was not observed in non-Px AK-treated rats. Treatment with AK alone resulted in significantly higher plasma Cr and BUN levels. Repeated administration of melatonin prevented the AK-induced elevation of plasma Cr and BUN levels. Morphologic damage to renal tubules as a result of AK was more severe in the renal cortex than in the medulla. The damage to the kidney induced by AK was reversed by melatonin in the Px rats. In conclusion, these results show that physiologic melatonin concentrations are important in reducing AK-induced renal damage, while pharmacologic concentrations of melatonin did not add to the beneficial effect.

The reactive oxygen species take role in pathogenesis of many diseases including hypoxia, hypercholesterolemia, atherosclerosis, nephropathy, hypertension, ischemia–reperfusion damage, and heart defects. The aim of this study was to evaluate whether crocin administration could protect kidney injury from oxidative stress in streptozotocin-induced diabetic rats. The rats were randomly divided into 3 groups each containing 10 animals as follows: group 1, control group; group 2, diabetes mellitus (DM) group; and group 3, DM + crocin group. At the end of the study, trunk blood was collected to determine the plasma levels of blood urea nitrogen (BUN) and creatinine (Cr). The kidney tissue was removed, and biochemical and histological changes were examined. Diabetes caused a significant increase in malondialdehyde (MDA) and xanthine oxidase (XO) activities and a decrease in glutathione (GSH) contents ( p < 0.01) when compared with control group in the rat kidneys. Crocin given to DM rats significantly decreased MDA ( p < 0.01) and XO ( p < 0.05) activities and elevated GSH ( p < 0.05) contents when compared with DM group. Plasma levels of BUN and Cr were significantly higher in the DM group when compared with the control group ( p < 0.01). Pretreatment of the DM animals with crocin decreased the high level of serum Cr and BUN. Control group was normal in histological appearance, but congestion, severe inflammation, tubular desquamation, tubular necrosis, and hydropic degeneration in tubular cells were observed in the DM group. Histopathological changes markedly reduced, and appearance of kidney was nearly similar to control group in DM + crocin group. Our results show that crocin could be beneficial in reducing diabetes-induced renal injury.

Objective To determine the expression patterns of prokineticin 1 (PROK1) and leukemia inhibitory factor (LIF) mRNA differ in peri-implantation endometrial tissue of women with idiopathic recurrent pregnancy loss (RPL) from normal fertile women. Design A case-control study. Setting University-based tertiary care center. Patient(s) 30 women with idiopathic RPL and 30 fertile controls. Intervention(s) Endometrial biopsies. Main Outcome Measure(s) Real-time polymerase chain reaction analysis for expression of PROK1 and LIF mRNA. Result(s) The expression of PROK1 and LIF was statistically significantly increased in the endometrium of the women with idiopathic RPL compared with the controls. Furthermore, increased LIF expression was observed in the endometrium of women with idiopathic RPL compared with controls. Conclusion(s) An increased mRNA expression of PROK1 and LIF could be one of the several abnormalities characterizing the endometrium in women with RPL.

Alzheimers Disease (AD), which is the most common reason for dementia, is an irreversible neurodegenerative brain disease. FEZ1 is a protein expressed in the brain. High expressions of FEZ1 mRNA have been interpreted as an indicator of high neural plasticity for memory and learning. This study was planned to determine the effect of melatonin deficiency (pinealectomy; PnX) on AD and to reveal its association with FEZ1. 30 male rats were used in the study. The rats were divided into three as SHAM, PnX+streptozotocin (STZ) and PnX+STZ+melatonin (MLT) groups. The pineal glands of rats were surgically removed (except SHAM group) and STZ was intracerebroventricularly (icv) administrated at the first and third days. MLT (10 mg/kg/day) was intraperitoneally (ip) injected 1 hour before the first STZ application and it was continued for 14 days. STZ and MLT solvents were applied to the rats in the SHAM group. At the end of the applications, Morris water maze (MWM) test was carried out the rats. At the end of MWM tests, the rats were sacrificed and their blood and hippocampus tissues were taken. FEZ1 gene expression and protein levels were determined from hippocampus tissue, while serum nonadrenaline, dopamine and serotonin levels were detected from blood samples. FEZ1 protein levels of PnX+STZ+MLT group were found to be statistically significantly lower than those of SHAM and PnX+STZ groups (p [Med-Science 2017; 6(2.000): 217-23]

This study was designed in order to investigate whether sun dried apricots have a preventive effect on the experimental cataract model formed by sodium selenite in rats. Fifty-nine Spraque-Dawley rat pups were divided into three groups. Group 1 (control group) consisted of twenty rat pups, born from the rats nourished ad libitum. Group 2 consisted of 18 newborn rats, born from the rats nourished ad libitum with 10% sun dried natural apricots. Group 3 consisted of 21 newborn rats, born from the rats nourished ad libitum. Subcutaneous (30nmol/gr) sodium selenite injection was applied to all the newborn rats except the control group (Group 1) on postpartum day 10. Cataract development was graded by slit-lamp examination and photography. Encapsulated lenses were analyzed for reduced glutathione (GSH) and malondialdehyde (MDA), a marker of lipid per oxidation. Lenses were also analyzed for total nitrite (TN). The presence of oxidative stress in selenite cataract development and its prevention by sun dried apricots.

Protective effect of caffeic acid phenethyl ester (CAPE) on ovary ischemia/reperfusion (IR) injury was investigated in this study. Twenty four New Zealand rabbits were divided into 4 groups as follows: group S served as sham. Group C was intraperitoneally injected with CAPE (8.5 mg/kg). In groups E + IR and C + IR, 1% ethanol and CAPE was given intraperitoneally before torsion, respectively. Then, the ovaries were subjected to IR in both groups. Ovary reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity in group E + IR were significantly reduced compared to that of group S. GSH level and GSH-Px activity was significantly increased in group C + I/R. Thiobarbituric acid reactive substances (TBARS) and catalase (CAT) activity in group E + I/R was significantly higher than in group S. CAT activity was decreased to normal levels by CAPE treatment in group C + I/R, while TBARS in group C + IR was significantly reduced compared to that of E + IR. According to histopathological examination, severe congestion, hemorrhage, edema and leukocyte infiltration were observed in E + I/R group. CAPE prominently reduced degenerative effects of IR injury thus it alleviates free radical damage. In conclusion, CAPE which is able to prevent IR-induced injury in the ovaries may be of therapeutic value before the surgical correction.

We investigated the regulation of antioxidant system under acetaminophen (AAP) toxicity. Twelve male New Zealand rabbits were divided into two groups with the following treatments: Group 1 animals were intraperitoneally injected with single saline (control). Group 2 animals were treated with intraperitoneal injection of AAP at a dose of 250 mg/kg body weight. Four hours following the treatments, blood samples were collected and the rabbits were sacrificed to collect liver samples. Hepatocellular damage was evaluated by aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as well as histopathological examinations and immunohistochemical analysis. Tissue-reduced glutathione (GSH), nitric oxide (NO·), and malondialdehyde (MDA) levels were also measured. mRNA expression levels of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) were measured by semi-quantitative RT-PCR. It was found that liver GSH was reduced significantly in AAP-treated rabbits (P

The efficacy of melatonin co-administration on aflatoxicosis in chicks was investigated. Ross PM3 breed chicks were divided into groups of 10 and given conventional feed. One of the groups was kept as a control (C), and the others were given 150 ppb aflatoxin (AF1), 300 ppb aflatoxin (AF2), 150 ppb aflatoxin plus 10 mg/kg/bwt melatonin (AF1+M), 300 ppb aflatoxin plus 10 mg/kg/bwt melatonin (AF2+M), 10 mg/kg/bwt melatonin (M), and 1% ethanol (E). After 21 day-treatment period, the chicks were sacrificed, liver and kidney tissues were collected, processed for immuno-histochemical staining, in situ TUNEL method, and biochemical analyses. Vacuolar degeneration, necrosis, bile duct hyperplasia in liver, and mild tubular degeneration in kidney were detected in AF groups. Pathological changes were markedly reduced in AF+M groups, and a microscopic view similar to group C was observed. Increased immunoreactivity against inducible nitric oxide synthase (iNOS) and nitrotyrosine was detected in AF groups compared to weak immunoreactivity in group C. Immunoreactivity in AF+M groups was markedly reduced compared to AF groups and was similar to group C in liver and kidney. Many apoptotic cells were detected in the livers of AF groups, whereas there were no apoptotic cells in AF+M groups. While reduced glutathione (GSH) levels in liver and kidney of AF groups were greatly reduced, malondialdehyde (MDA) levels increased. With melatonin co-administration, the levels of GSH and MDA approached to the values of group C. These results indicated that nitrosative tissue degeneration caused by aflatoxin could be greatly reduced by melatonin supplementation in chicks.

WOS: 000241221200016 PubMed ID: 16758301 The aim of this study was to investigate the effects of chronic ethanol intake and cigarette smoke exposure on rat kidney. The animals were divided into four experimental groups: (1) the control group (C), (2) the ethanol group (E), (3) the cigarette smoke group (CS), and (4) the cigarette smoke plus ethanol group (CS+E). Rats in E, CS and CS+E groups were treated with ethanol and/or cigarette smoke for 6 months. The animals were killed and the kidneys were removed to determine the activity of xanthine oxidase (XO), myeloperoxidase (MPO) and the levels of nitric oxide (NO). Histopathological and immunohistochemical analysis were performed in kidney tissues. The activity of XO/g protein were 2.8 +/- 0.3, 5.2 +/- 0.3, 3.2 +/- 0.1, and 7.4 +/- 0.7 U for C, E, CS and CS+E groups, respectively. In groups E, and CS+E, the XO values were significantly higher than in group C (P < 0.05). The increase in XO activity of CS was not significantly different from group C (P > 0.05). There was a significant increase in XO activity of group CS+E as compared to CS and E groups (P < 0.05), and also a significant difference in XO activity between E and CS was observed (P < 0.05). The activity of MPO/g protein were 13.5 +/- 0.6, 16.2 +/- 1.1, 14.7 +/- 1.1, 23.8 +/- 0.9 U for C, E, CS, and CS+E groups, respectively. While MPO activity of kidneys from group CS+E were significantly higher as compared to C, CS, and E groups (P < 0.05), there was no significant difference among the groups of C, CS, E (P > 0.05). The levels of NO/g wet tissue were 347.7 +/- 8.5, 261.1 +/- 4.8, 329.8 +/- 5.6, and 254.2 +/- 3.8 nmol for C, E, CS, and CS+E groups, respectively. In groups of E and CS+E, the NO values were significantly lower than that of group C animals (P < 0.05). Although we detected lower NO levels in the E and CS+E groups than in CS group (P < 0.05), a significant difference in NO levels between CS+E and E groups was not observed. In the histopathological analysis of the kidney slices, severe degenerations in kidney tissues of group CS, E, CS+E were observed. Generally, the histological changes in kidney of CS+E and E groups were more severe than those observed in CS alone. While we observed a strong immunoreactivity for anti-nitrotyrosine antibody in kidneys of group CS+E, examination of sections from rat kidneys in group E revealed moderate staining. On the other hand, group CS had very little immunostaining. There was no immunostaining in group C. We concluded that chronic ethanol administration and cigarette smoke exposure may cause oxidative and nitrosative stress which lead to rat kidney damage.

Previous observations demonstrated that physiological levels of melatonin, the pineal secretory product, are important in protecting against oxidative stress-induced tissue damage. We investigated the effects of pinealectomy and administration of exogenous melatonin on liver tissue in rats. Pinealectomized (Px) and sham-operated (non-Px) rats were used. We evaluated structural changes, reduced glutathione (GSH) levels and malondialdehyde (MDA) levels. Rats were divided into three groups (10 rats in each group): control (non-Px), Px+vehicle and Px+melatonin (4 mg/kg given daily intraperitoneally for 10 days). Liver GSH levels were significantly lower in Px rats than in the control group. Melatonin administration significantly increased GSH levels (p0.05). Px caused a significant increase in MDA levels as compared with the control group and melatonin administration to Px rats significantly reduced MDA levels in the liver (p0.05). Sinusoidal dilatation to a varying degree developed in all Px rats. Severity of mononuclear cell infiltration and sinusoidal congestion were lower in Px+melatonin group than in the Px group. These findings suggest that a significant increase in oxidative and structural changes occur in rat livers after pinealectomy, which can be diminished by melatonin treatment.

The aim of this study was to investigate the effects of chronic ethanol intake and cigarette smoke exposure on rat kidney. The animals were divided into four experimental groups: (1) the control group (C), (2) the ethanol group (E), (3) the cigarette smoke group (CS), and (4) the cigarette smoke plus ethanol group (CS+E). Apart from the control group, these were treated with ethanol and/or cigarette smoke for 6 months. The animals were killed and the kidneys removed to determine the levels of reduced glutathione (GSH) and malondialdehyde (MDA) and for histopathological analysis. The levels of GSH/g wet tissue were 1.58+/-0.09 micro mol, 0.91+/-0.05 micro mol, 1.14+/-0.06 micro mol, and 0.82+/-0.04 micro mol for C, E, CS, and CS+E, respectively. In groups of E, CS, and CS+E, the GSH values were significantly lower than that of group C animals ( P0.05). Although, we detected lower GSH levels in the CS+E than the CS group ( P0.05), a significant difference in GSH levels between CS+E and E was not observed. The levels of MDA/g wet tissue were 40.1+/-3.4 nmol, 71.4+/-2.8 nmol, 64.0+/-3.6 nmol, and 76.5+/-4.3 nmol, for C, E, CS and CS+E, respectively. In E, CS, and CS+E, the MDA values were significantly higher than in group C ( P0.05). The increase in MDA levels in CS+E were not significantly different from groups E or CS. Histopathological analysis of the kidney slices showed severe degeneration of the tissues. Advanced hydropic degeneration of kidney tubules was clearly observed in the CS group. In group E, advanced tubular and interstitial damage, mononuclear cell infiltration and tubular thyroidization were clearly visible. In group CS+E, an intense inflammatory cell infiltration was detected under the transitional epithelium. We conclude that chronic exposure to ethanol and cigarette smoke may cause an oxidative burst in rat kidney by increasing the formation of reactive oxygen species.

Reactive oxygen species have been implicated in the pathophysiology of renal ischemia reperfusion (I/R) injury. The pineal secretory product melatonin is known to be a potent free radical scavenger and antioxidant. This study was designed to investigate the effects of physiological and pharmacological concentrations of melatonin on I/R injury. Rats were pinealectomized (Px) or sham-operated (control) 2 months before the I/R studies. There were eight groups of eight rats each. After a right nephrectomy to produce damage, left renal vessels were occluded for 60 min, followed by 24 h reperfusion, in rats. Malondialdehyde (MDA) levels resulting from I/R were significantly higher in the pinealectomized rats than in the control group. Melatonin administration (4 mg kg(-1) i.p. either before ischemia or reperfusion) to Px and sham-operated rats significantly reduced the MDA values and returned them to the control values. Morphological changes in the groups were similar to the MDA levels. Serum levels of blood urea nitrogen and creatine were unchanged. These results suggest that physiological and pharmacological melatonin concentrations are important for the reduction of I/R-induced damage. We also demonstrated that melatonin, even when administrated just before reperfusion, had a protective effect on I/R injury. It would seem valuable to test melatonin in clinical trials for the prevention of possible I/R injury.