Oxidative Stress In Female Rats Research Articles

L-arginine supplementation attenuates ovarian oxidative stress in female rats subjected to chronic intermittent hypoxia.

Systemic and organ-specific oxidative stress triggered by hypoxia is suggested to play a key role in germ cell apoptosis and DNA damage. This study was designed to investigate the impact of chronic intermittent hypoxia (CIH) on female fertility and evaluate the potential antioxidant effect of L-arginine (L-Arg) supplementation. Adult female rats were allocated into three groups: controls (normoxic), hypoxic and hypoxic supplemented with L-Arg. After 12 weeks; hematocrit value was determined, body weight (BW) and ovarian weight were measured for the calculation of the gonado-somatic index. Plasma levels of luteinizing hormone (LH) and progesterone were estimated. Ovarian tissue malondialdehyde (MDA) and catalase were assessed, and caspase-3 enzyme expression was detected by immunohistochemistry. Compared to controls, CIH resulted in increased oxidative stress in the ovarian tissue, decreased ovarian weight, and increased frequency of irregular cycles and higher plasma level of LH in rats with either regular or irregular ovarian cycles. Histological examination of ovarian sections revealed areas of degeneration, atretic follicles, interstitial edema, congested vessels and inflammatory cell infiltration. Immunohistochemistry confirmed the presence of apoptosis by increased caspase-3 expression. Hypoxic rats pre-treated with L-Arg showed increased BW and ovarian weight, decreased ovarian tissue MDA and plasma LH accompanied by a lower incidence of irregular cycles and mortality. The histological picture was improved and caspase-3 expression was reduced. Oxidative stress caused by CIH is detrimental to the structure and function of the corpus luteum with an increased risk of reduced fertility. L-Arg supplementation increases antioxidant capacity and improves hypoxia-induced fertility disorders.

"K-Powder" Exposure during Adolescence Elicits Psychiatric Disturbances Associated with Oxidative Stress in Female Rats.

Ketamine, also called 'K-powder' by abusers, an analog of phencyclidine, primarily acts as an antagonist of N-methyl-D-aspartic acid (NMDA) receptors, therapeutically used as an anesthetic agent. Ketamine also stimulates the limbic system, inducing hallucinations and dissociative effects. At sub-anesthetic doses, ketamine also displays hallucinatory and dissociative properties, but not loss of consciousness. These behavioral consequences have elicited its recreational use worldwide, mainly at rave parties. Ketamine is generally a drug of choice among teenagers and young adults; however, the harmful consequences of its recreational use on adolescent central nervous systems are poorly explored. Thus, the aim of the present study was to characterize the behavioral and biochemical consequences induced by one binge-like cycle of ketamine during the early withdrawal period in adolescent female rats. Adolescent female Wistar rats (n = 20) received intraperitoneally administered ketamine (10 mg/kg/day) for 3 consecutive days. Twenty-four hours after the last administration of ketamine, animals were submitted to behavioral tests in an open field, elevated plus-maze, and forced swimming test. Then, animals were intranasally anesthetized with 2% isoflurane and euthanized to collect prefrontal cortex and hippocampus to assess lipid peroxidation, antioxidant capacity against peroxyl radicals, reactive oxygen species, reduced glutathione, and brain-derived neurotrophic factor (BDNF) levels. Our results found that 24 h after recreational ketamine use, emotional behavior disabilities, such as anxiety- and depression-like profiles, were detected. In addition, spontaneous ambulation was reduced. These negative behavioral phenotypes were associated with evidence of oxidative stress on the prefrontal cortex and hippocampus.

Chronic mercury exposure induces oxidative stress in female rats by endothelial nitric oxide synthase uncoupling and cyclooxygenase-2 activation, without affecting oestrogen receptor function.

Mercury has been shown to be a significant health risk factor and is positively associated with cardiovascular diseases. Evidence reveals that men are more likely to develop cardiovascular diseases than women during reproductive age. However, the effects of mercury in females remain poorly investigated, despite the finding that female hormones demonstrate a cardioprotective role. In the present study, we evaluated whether chronic mercury chloride exposure could alter blood pressure and vascular function of the female rat aorta. Ten-week-old female Wistar rats were divided into two groups: control (vehicle) and mercury treated (first dose of 4.6 μg/kg, subsequent daily doses of 0.07 μg/kg), im. Mercury treatment did not modify systolic blood pressure (SBP) but increased vascular reactivity due to the reduction of nitric oxide bioavailability associated with the increase in reactive oxygen species from endothelial nitric oxide synthase (eNOS) uncoupling. Furthermore, increased participation of the cyclooxygenase-2 pathway occurred through an imbalance in thromboxane 2 and prostacyclin 2. However, the oestrogen signalling pathway was not altered in either group. These results demonstrated that chronic exposure to mercury in females induced endothelial dysfunction and, consequently, increased aortic vascular reactivity, causing vascular damage to the female rat aorta and representing a risk of cardiovascular diseases.

The negative effect of desflurane on reproductive capacity in female rats.

The aim of this study was to determine the effect of desflurane on reproductive capacity in female rats through a study of biochemical evaluations. After experimental procedure, the blood samples of female rats were collected, and the malondialdehyde, interleukin‑1‑beta, total glutathione and superoxide dismutase levels were measured to evaluate oxidative stress. In addition to biochemical evaluations, the reproductive performance of the experimental groups was also examined. The results of our study demonstrated that in blood samples of desflurane‑treated groups of rats, the parameters indicating oxidative stress and inflammation increased, and antioxidant parameters decreased (p < 0.05). It was also proven that repeated desflurane doses caused infertility in female rats, prolonged the gestation period and reduced the number of offspring. This study showed that recurrent desflurane application can cause infertility problems through oxidative stress in female rats (Tab. 3, Fig. 1, Ref. 25).

Effect of khat on ovarian oxidative stress in female rats

Oxidative stress (OS) greatly influences the reproductive health in female mammalian animals. The study used femaleWistar rats weighing 200 ± 10 g grouped and administered orally as, control groups (1ml CMC), (0.5 g/100ml carboxy methyl cellulose)) and Khat groups (1ml khat extract) (150mg/kg) each for 3 and 6 weeks. Ovaries from each group at the two experimental periods used for the determination of ovarian OS markers. Results showed significant decrease in superoxide dismutase (SOD) enzyme activities and nitric oxide (NO) levels and reduced glutathione/oxidized glutathione (GSH/GSSG) levels as well as significant increase in malondialdehyde (MDA) contents in khat groups after 3 and 6weeks of treatment as compared to their corresponding control values. Results overt that ovaries from rats subjected to khat extract were under OS due to the imbalance between ROS production and anti-oxidants.

Effect of Exposure to Mixture of Heavy Metals Arsenic, Cadmium and Lead on Reproductive Function and Oxidative Stress in Female Rats

Background : Toxicological consequences arising from exposure to mixtures of heavy metals especially at low, chronic and environmentally relevant doses are poorly recognised. In the present study, we evaluated effects of chronic exposure to combinations of three metals arsenic (As), cadmium (Cd) and lead (Pb) present frequently in drinking water on reproductive function and oxidative damage caused to reproductive organs of female rats. Method : Female rats were exposed to mixture of metals (As, Cdand Pb) for 90 consecutive days. The gain in body weight and weight of reproductive organs were recorded following autopsy on 91 stday. The oestrus cycle were monitored during entire treatment period. Numbers of corpora lutea, implantation sites, live fetus and survival of the fetus were evaluated in rats mated successfully with untreated male after completion of their respective treatment. Ovarian cholesterol, protein, ascorbic acid and enzyme Δ 5 -3β HSD levels were estimated. Serum levels of steroid hormones oestrogen and progesterone were estimated. Histopathological picture of both ovary and uterus were assessed. Levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidise (GPX) activity, amount of reduced glutathione (GSH) and malondyaldehyde (MDA) in blood, ovary and uterus were measured as biomarkers of oxidative stress. Results : The treated rats showed reduced body weight gain and reduction in the weight of ovary and uterus. Oestrus cycle was disrupted with continuous diestrous in treated animals. Number of corpora lutea, implantation sites and live fetus and the survival of fetus evaluate were reduced significantly in treated groups. The levels of ovarian cholesterol and ascorbic acid increased in treated rats with decrease Δ5 -3β HSD level. There was reduction in serum level of both the ovarian steroid hormones oestrogen and progesterone. The protein levels did not differ between the groups. There was a significant increase in levels of MDA and decrease in levels of all the antioxidant enzymes in treated group. Conclusion : The results revealed there was disruption to reproductive functions with decrease in stereoidogenic activity and associated oxidative stress in female rats treated with combination of mixture of metals (Cd, As and Pb) at low dose for 90 consecutive days.

Protective effects of oil of Sardinella pilchardis against subacute chlorpyrifos-induced oxidative stress in female rats

ABSTRACTThis study was conducted to evaluate the protective effects of Sardinella pilchardis oil and vitamin E against chlorpyrifos- (CPF-) induced liver, kidney, and brain oxidative damage in female rats. The rats were divided into 6 experimental groups: the control group, the group treated with fish oil, the group that received fish oil for 2 weeks and CPF orally for 7 days, the group treated only with CPF, the group treated with vitamin E for 2 weeks and CPF for 7 days, and the group treated with vitamin E. Oral exposure to CPF induced a significant increase in serum biochemical parameters; hepatic, kidney, and brain LPO; and a decrease in superoxide dismutase, catalase, and glutathione peroxidase activities. Fish oil or vitamin E decreased significantly the mentioned biochemical parameters as compared to rats treated with CPF alone. This study suggests that fish oil has an ameliorative effect for the alleviation of the oxidative damage induced by CPF.

Tributyltin chloride induces renal dysfunction by inflammation and oxidative stress in female rats

Tributyltin chloride (TBT) is an organometallic pollutant that is used as a biocide in antifouling paints. TBT induces several toxic and endocrine-disrupting effects. However, studies evaluating the effects of TBT on renal function are rare. This study demonstrates that TBT exposure is responsible for improper renal function as well as the development of abnormal morphophysiology in mammalian kidneys. Female rats were treated with TBT, and their renal morphophysiology was assessed. Morphophysiological abnormalities such as decreased glomerular filtration rate and increased proteinuria levels were observed in TBT rats. In addition, increases in inflammation, collagen deposition and α-smooth muscle actin (α-SMA) protein expression were observed in TBT kidneys. A disrupted cellular redox balance and apoptosis in kidney tissue were also observed in TBT rats. TBT rats demonstrated reduced serum estrogen levels and estrogen receptor-α (ERα) protein expression in renal cortex. Together, these data provide in vivo evidence that TBT is toxic to normal renal function and that these effects may be associated with renal histopathology complications, such as inflammation and fibrosis.

Effect of sodium arsenite on reproductive organs of female Wistar rats

ABSTRACTThe present study was performed to investigate the subchronic effect of sodium arsenite on female Wistar rats. Mature female rats were divided into 4 groups of 12 animals each. Group I received distilled water, whereas the other 3 groups received sodium arsenite at 10, 30, and 50 µg/L doses for 60 days through drinking water. Half of the animals from each group were dissected after 30 days and the remaining after 60 days. A disruption in estrous cycle was observed with prolonged diestrous and metestrous phases. A significant increase in ovarian surface epithelium and follicular atresia was observed in treated rats (p ≤ .05). A significant decrease (p ≤ .05) in the uterine myometrium was observed. A significant increase (p ≤ .05) in the levels of lipid peroxidation along with decrease in the activities of antioxidant enzymes was observed. The results revealed that subchronic exposure of sodium arsenite causes degenerative changes in reproductive organs and induces oxidative stress in female rats.

Sex-dependent hepatic transcripts and metabolites in the development of glucose intolerance and insulin resistance in Zucker diabetic fatty rats

Male Zucker diabetic fatty (mZDF) rats spontaneously develop type 2 diabetes, whereas females only become diabetic when fed a diabetogenic high-fat diet (high-fat-fed female ZDF rat, HF-fZDF). The aim of this study was to investigate if differences in liver functions could provide clues to this sex difference. Non-diabetic obese fZDF rats were compared with either mZDF or HF-fZDF regarding hepatic molecular profiles, to single out those components that might be protective in the females. High-fat feeding in fZDF led to enhanced weight gain, increased blood glucose and insulin levels, reduced insulin sensitivity and a trend towards reduced glucose tolerance, indicative of a prediabetic state. mZDF rats were diabetic, with low levels of insulin, high levels of glucose, reduced insulin sensitivity and impaired glucose tolerance. Transcript profiling and capillary electrophoresis time-of-flight mass spectrometry were used to indentify hepatic transcripts and metabolites that might be related to this. Many diet-induced alterations in transcript and metabolite levels in female rats were towards a 'male-like' phenotype, including reduced lipogenesis, increased fatty acid (FA) oxidation and increased oxidative stress responses. Alterations detected at the level of hepatic metabolites, indicated lower capacity for glutathione (GSH) production in male rats, and higher GSH turnover in females. Taken together, this could be interpreted as if anabolic pathways involving lipogenesis and lipid output might limit the degree of FA oxidation and oxidative stress in female rats. Together with a greater capacity to produce GSH, these hepatic sex differences might contribute to the sex-different development of diabetes in ZDF rats.

Chronic Exposure to Arsenic in Tap Water Reduces Acetylcholine-induced Relaxation in the Aorta and Increases Oxidative Stress in Female Rats

The aim of this work is to determine whether consuming tap water containing arsenic (20 microg/L) alters oxidative stress levels in female rats and changes vascular response. Whereas nitric oxide produces complete relaxation, arsenic (7 months of exposure) impairs the acetylcholine-induced endothelial relaxation in the rat aorta compared with control rats. Arsenic exposure results in a marked elevation in reactive oxygen species in blood, and delta-aminolevulinic acid dehydratase activity, which is a sensitive biomarker for arsenic toxicity and oxidative stress, is significantly decreased in erythrocytes from 7-month-old rats. Diastolic blood pressure increases significantly in 7-month-old arsenic-treated versus control rats. The percentage of change in peripheral resistance increases. The results indicate that chronic environmental exposure to low levels of arsenic alters the release of vasoactive substances, causes changes in oxidative stress, and increases blood pressure in female rats.

Estradiol Protects Against Oxidative Stress Induced by Chronic Variate Stress

Neurochemical gender-specific effects have been observed following chronic stress. The aim of this study was to verify the effects of chronic variable stress on free radical production (evaluated by DCF test), lipoperoxidation (evaluated by TBARS levels), and total antioxidant reactivity (TAR) in three distinct structures of brain: hippocampus, cerebral cortex and hypothalamus of female rats, and to evaluate whether the replacement with estradiol in female rats exerts neuroprotection against oxidative stress. Results demonstrate that chronic stress had a structure-specific effect upon lipid peroxidation, since TBARS increased in hypothalamus homogenates of stressed animals, without alterations in the other structures analyzed. Estradiol replacement was able to counteract this effect. In hippocampus, estradiol induced a significant increase in TAR. No differences in DCF levels were observed. In conclusion, the hypothalamus is more susceptible to oxidative stress in female rats submitted to chronic variable stress, and this effect is prevented by estradiol treatment.

Dietary Copper Primarily Affects Antioxidant Capacity and Dietary Iron Mainly Affects Iron Status in a Surface Response Study of Female Rats Fed Varying Concentrations of Iron, Zinc and Copper

This study was designed to examine the interactions among dietary iron (Fe), copper (Cu), and zinc (Zn) and their effects on Fe status and oxidative stress in female rats. In a three-factor central composite response surface design, rats were assigned to 15 groups and fed modified AIN-93G basal diets with varying amounts of Fe and Zn (7.0, 15.5, 45.8, 135.6, or 300 μg/g diet) and Cu (0.5, 1.1, 3.2, 9.2, or 20 μg/g diet) for 6 wk. Variations in hemoglobin, hematocrit, and serum ferritin were mainly related to dietary Fe. Liver nonheme Fe was directly affected by dietary Fe and was slightly attenuated by interactions between Cu and Zn, and Zn and Fe. Serum ceruloplasmin activity was primarily determined by an interaction between Cu and Zn with substantial moderation by the quadratic effect of dietary Cu. Liver and heart total superoxide dismutase (SOD) and Cu/Zn SOD activities were directly affected by dietary Cu. Dietary Fe was the only significant, yet weak, predictor of liver thiobarbituric acid reactive substances (TBARS) and vitamin E content and serum triacylglycerols. Variability in serum Cu was mostly determined by the interaction between Cu and Fe, with modification from the quadratic effect of dietary Cu. Serum Zn varied with dietary Zn with a small negative influence from the interaction between Cu and Fe. In summary, Fe status was minimally influenced by dietary Zn or Cu, and Fe intakes 10-fold greater than required did not induce overt oxidative stress in female rats. In addition, measures of antioxidant capacity were primarily influenced by dietary Cu and were optimal at moderate intakes of this micronutrient.

2,3,7,8-Tetrachlorodibenzo- p-dioxin-induced oxidative stress in female rats

Oxidative stress may play a role in the toxic manifestations of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD). Therefore, the time-dependent effects of 100 μg TCDD/kg on various indices of oxidative stress including lipid peroxidation, DNA damage, membrane fluidity, calcium homeostasis, nonprotein sulfhydryl content, and NADPH content of hepatic subcellular fractions of female rats were followed for 12 days. Increases in lipid peroxidation of 400–500% occurred in mitochondrial and microsomal membranes and nuclei, with maximum increases occurring 5–6 days post-treatment. Decreases in the nonprotein sulfhydryl content of mitochondrial and microsomal fractions of approximately 80% were observed by Day 12 post-treatment Membrane fluidity gradually decreased following administration of TCDD, with decreases of 30–40% being observed in mitochondria, microsomes, and plasma membranes. A sharp increase in the incidence of hepatic nuclear DNA single strand breaks was observed 3 days after treatment with an increase of approximately 600% by Day 9. Following the administration of TCDD, increases of 70–80% occurred in the calcium content of mitochondria and microsomes. An 18% increase in cytosolic calcium was present 12 days after the administration of TCDD. Cytosol and mitochondria both exhibited an initial increase in NADPH content following administration of TCDD, but by Day 12 both had decreased to approximately two-thirds of control values. The results clearly demonstrate that TCDD administration induces an oxidative stress in rat liver. The most pronounced effects were observed in membrane lipid peroxidation and DNA damage with gradual changes being observed in calcium and nonprotein sulfhydryl contents and membrane fluidity.