Lipid peroxidation in ovariectomized and pinealectomized rats: the effects of estradiol and progesterone supplementation

In the present study, we investigated the effect of estradiol and progesterone supplementation on oxidant and antioxidant parameters of renal tissue in ovariectomized and pinealectomized rats. The study was carried out on 36 adult, Sprague-Dawley strain female rats, 6 months of age and weighing 200-250 g. The rats were divided into six groups, each group included six rats: Group 1: Sham-ovariectomized (Sham-Ovx); Group 2: Ovariectomized (Ovx); Group 3: Ovx and estradiol (E) and progesterone (P) supplemented (Ovx+E-P); Group 4: Ovariectomized and sham pinealectomy (Ovx+sham Pnx); Group 5: Ovariectomized+Pinealectomized (Ovx+Pnx); Group 6: Ovariectomized+Pinealectomized+Hormone Supplemented group (Ovx+Pnx+E-P). The levels of malondialdehyde (MDA), reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) were analysed in renal tissues of rats. The highest and the lowest levels of MDA were determined in Groups 5 and 1 respectively (p < 0.001). However, GSH and GSH-Px levels demonstrated statistically important decreases in groups 2, 4, 5 (p < 0.001). The findings of this study demonstrate that ovariectomy leads to oxidative damage in renal tissue. Pinealectomy in addition to ovariectomy greatly increases the oxidative damage. However, female sex hormones supplementations to the Ovx and/or Ovx+Pnx rats protected against lipid peroxidation by activating the antioxidant system.     

The influence of estradiol and progesterone and melatonin supplementation on TNF-alpha levels in ovariectomized and pinealectomized rats

The aim of this study was to investigate the effect of estradiol and progesterone and melatonin supplementation on TNF-alpha levels in ovariectomized and pinealectomized rats. The study was carried out on 42 adult, Spraque-Dawley strain female rats aged 6 months and weighing 200-250 grams. The rats were divided into 6 groups, each group contained 7 rats. Group 1: Sham-ovariectomized (Sham-Ovx), Group 2: Ovariectomized (Ovx), Group 3: Ovx and estradiol (E) and progesterone (P) supplemented (Ovx+E-P) group, Group 4: Ovx+E-P+Melatonin (M) supplemented group, Group 5: Ovx Pinealectomized (Pnx) group, Group 6: Ovx - Pnx+E-P supplemented group. Serum TNF-alpha levels were determined after 4 weeks application period. Group 6 (Ovx-Pnx+E-P) has the highest serum TNF-alpha compared with other groups while group 2 (ovariectomized), has the lowest levels (P<0.001). Group 5 was higher than groups 1, 2, 3 and 4 (P <0.001). The results of the study show that ovariectomy reduces the serum level of TNF-alpha, but estradiol and progesterone application prevents this reduction in ovariectomized rats. However, pinealectomy intensifies the increases in TNF-alpha levels in ovariectomized and estradiol and progesterone supplemented rats, whereas melatonin reduces TNF-alpha levels in ovariectomized rats.     

17β-Estradiol and Vitamin E Modulates Oxidative Stress-Induced Kidney Toxicity in Diabetic Ovariectomized Rat

The aim of this study was to investigate the effects of vitamin E (alpha-tocopherol) and 17β-estradiol (E(2)) supplementation on malondialdehyde (MDA), glutathione (GSH), vitamin A, beta carotene, selenium-dependent glutathione peroxidase (GSH-Px), zinc-dependent superoxide dismutase (SOD), and copper/zinc-dependent catalase (CAT) values in the kidney of ovariectomized (OVX) diabetic rats. Forty-two female rats were randomly divided into seven equal groups as follows: group I, control; group II, OVX; group III, OVX+E(2); group IV, OVX+E(2)+alpha-tocopherol; group V, OVX+diabetic; group VI, OVX+diabetic+E(2); and group VII, OVX+diabetic+E(2)+alpha-tocopherol. E(2) (40?μg?kg(-1)/day) and alpha-tocopherol (100?μg?kg(-1)/day) were given. Bilateral ovariectomy was performed in all groups except group I. After 4?weeks, antioxidant and MDA levels in the kidney for all groups were analyzed. GSH-Px, CAT, SOD, GSH levels, vitamin A, and beta carotene levels were decreased in OVX group compared to those in the control group but MDA level was elevated via ovariectomy. However, E(2) and E(2)+alpha-tocopherol supplementations in OVX group was associated with an increase in the GSH-Px, GSH, CAT and Zn-SOD values, vitamin A, and beta carotene levels but a decrease in MDA levels in kidney. The MDA levels in the kidney of diabetic OVX rats were found higher than those in the control and OVX groups. However, GSH, GSH-Px, CAT, SOD, vitamin A, and beta carotene levels in kidney were lower in OVX diabetic rats. On the other hand, E(2) and E(2)+alpha-tocopherol supplementations to OVX diabetic rats have caused an increase in GSH-Px, CAT and SOD, GSH, vitamin A, and beta carotene levels but a decrease in MDA levels. In conclusion, the E(2) and E(2)+alpha-tocopherol supplementations to diabetic OVX and OVX rats may strengthen the antioxidant defense system by reducing lipid peroxidation, and therefore they may play a role in preventing renal disorders.     

Apple Cider Vinegar Modulates Serum Lipid Profile,Erythrocyte, Kidney,and Liver Membrane Oxidative Stress in Ovariectomized Mice Fed High Cholesterol

The purpose of this study was to investigate the potentially beneficial effects of apple cider vinegar (ACV) supplementation on serum triglycerides, total cholesterol, liver and kidney membrane lipid peroxidation, and antioxidant levels in ovariectomized (OVX) mice fed high cholesterol. Four groups of ten female mice were treated as follows: Group I received no treatment and was used as control. Group II was OVX mice. Group III received ACV intragastrically (0.6 % of feed), and group IV was OVX and was treated with ACV as described for group III. The treatment was continued for 28 days, during which the mice were fed a high-cholesterol diet. The lipid peroxidation levels in erythrocyte, liver and kidney, triglycerides, total, and VLDL cholesterol levels in serum were higher in the OVX group than in groups III and IV. The levels of vitamin E in liver, the kidney and erythrocyte glutathione peroxidase (GSH-Px), and erythrocyte-reduced glutathione (GSH) were decreased in group II. The GSH-Px, vitamin C, E, and β-carotene, and the erythrocyte GSH and GSH-Px values were higher in kidney of groups III and IV, but in liver the vitamin E and β-carotene concentrations were decreased. In conclusion, ACV induced a protective effect against erythrocyte, kidney, and liver oxidative injury, and lowered the serum lipid levels in mice fed high cholesterol, suggesting that it possesses oxidative stress scavenging effects, inhibits lipid peroxidation, and increases the levels of antioxidant enzymes and vitamin.     

The effect of estradiol and progesterone application on leptin concentration in ovariectomized rats

The aim of the present study was to investigate the effects of estradiol and progesterone application on leptin secretion in ovariectomised rats. The study included 30 adult female Sprague-Dawley rats. Rats were divided into three groups as follows: Group 1; Sham ovariectomy group (n=10), Group 2; Ovariectomy group (n=10), Group 3; Ovariectomized and estradiol propionate (450 microg/kg rat) and medroxyprogesterone acetate (15 mg/kg rat) supplemented group (n=10). One week after ovariectomy, rats in Group 3 were injected estradiol and progesterone for 4 weeks. Twenty-four hours after the last injection, rats were decapitated and blood samples were collected for leptin analysis. Serum leptin levels in Group 2 were found significantly higher than those in Groups 1 and 3 (p<0.01), while those in Group 3 were significantly lower when compared to Group 1 (p<0.0 1). The findings of the present study have shown that ovariectomy led to a significant increase in leptin levels. However, administration of estradiol and progesterone in combination following ovariectomy inhibites increases of leptin levels.     

Glutathione and lipid peroxide levels in rat liver following administration of methapyrilene and analogs

The possibility was examined that the induction of tumors in rat liver by feeding methapyrilene, which is not mutagenic, is related to effects on glutathione levels and lipid peroxidation. Fischer 344 rats were given single-dose and multiple-dose treatments with the anti-histamine methapyrilene (MP), which is carcinogenic in rats, and with two non-carcinogenic analogs, methafurylene (MF) and thenyldiamine (TD) and the effects on malonaldehyde (MDA) formation and glutathione (GSH) levels in the liver were investigated. After a single dose, MDA levels were increased at 6 h by MF and TD and at 24 h by MP. MDA levels returned to normal after 30 h with MP and MF, but not with TD. Levels of MDA (and other TBA-reactive products) after four daily treatments were most elevated by TD, less elevated by MP, and were lowered by MF. Forty-two hours following treatment with both MP and MF, MDA levels had returned to normal, but in TD-treated animals MDA remained high. GSH levels were highest after MF and MP, and remained high at 42 h, but TD induced only a small increase. There appears to be increased lipid peroxidation in the liver as a result of treatment of rats with MP, MF and TD. The greater response induced by TD, as well as the increased liver GSH levels after repeated administration of all three drugs indicate that lipid peroxidation in rat liver is not a particular effect related to the liver carcinogen methapyrilene.     

莲心碱对实验性高脂血症大鼠血脂及脂质过氧化的影响

本文研究莲心碱对实验性高脂血症大鼠血脂和抗氧化能力的影响.将32只大鼠随机分为4组,对照组饲喂基础饲料;诱导组饲喂高脂饲料;试验组给予高脂饲料+莲心碱灌胃2.5和5.0 mg·kg-1.测血清中血脂和丙二醛(MDA)水平,以及谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)活性;取肝脏测绝对和相对肝重及MDA含量.结果表明莲心碱可显著降低实验性高脂血症大鼠血清中总胆固醇、甘油三酯、低密度脂蛋白胆固醇水平和动脉粥样硬化指数;显著升高血清高密度脂蛋白胆固醇、GSH-Px和SOD水平;同时还可显著降低血清和肝脏中MDA的含量;其绝对和相对肝重均低于诱导组.     

Effect of Selenium Supplementation on Lipid Peroxidation,Antioxidant Enzymes,and Lactate Levels in Rats Immediately After Acute Swimming Exercise

The present study aims to evaluate the effect of selenium supplementation on lipid peroxidation and lactate levels in rats subjected to acute swimming exercise. Thirty-two adult male rats of Sprague–Dawley type were divided into four groups. Group 1, control; group 2, selenium-supplemented; group 3, swimming control; group 4, selenium-supplemented swimming group. The animals in groups 2 and 4 were supplemented with (i.p.) 6 mg/kg/day sodium selenite for 4 weeks. The blood samples taken from the animals by decapitation method were analyzed in terms of erythrocyte-reduced glutathione (GSH), serum glutathione peroxidase (GPx) and superoxide dismutase (SOD), and plasma malondialdehyde (MDA) and lactate using the colorimetric method, and serum selenium values using an atomic emission device. In the study, the highest MDA and lactate values were found in group 3, while the highest GSH, GPx and SOD values were obtained in group 4 (p < 0,001). Group 2 had the highest and group 3 had the lowest selenium levels (p < 0,001). Results of the study indicate that the increase in free radical production and lactate levels due to acute swimming exercise in rats might be offset by selenium supplementation. Selenium supplementation may be important in that it supports the antioxidant system in physical activity.     

Effects of ciprofloxacin on fetal rat liver during pregnancy and protective effects of quercetin

Urinary tract infections are common in pregnant women and ciprofloxacin frequently is used as a broad spectrum antibiotic. It has been suggested that ciprofloxacin causes liver damage in fetuses. Quercetin is a flavonoid with antioxidant properties. We investigated the efficacy of quercetin treatment for preventing fetal liver damage caused by ciprofloxacin. Pregnant rats were divided into four groups: untreated control group (C), 20 mg/kg quercetin for 21 days group (Q), 20 mg/kg twice/day ciprofloxacin for 10 days group (CP), and 20 mg/kg, ciprofloxacin + quercetin for 21 days group (CP + Q). Fetal livers were removed on day 21 of gestation to measure antioxidants and for histological observation. Malondialdehyde (MDA) and glutathione (GSH) levels, and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were measured in tissue samples. GSH-Px, SOD and CAT activities were significantly lower in the CP group compared to group C. A significant increase in MDA was observed in the CP group compared to group C. There was no significant difference in GSH levels in any group. MDA levels were lower and CAT, SOD and GSH-Px enzyme activities were higher in the CP + Q group compared to group CP. Liver samples of the CP group exhibited central vein dilation, portal vein congestion, pyknotic nuclei and cytoplasmic vacuolization in some hepatocytes. Histological changes were less prominent in the rats treated with quercetin. Use of ciprofloxacin during pregnancy caused oxidative damage in fetal liver tissue. Oxidative stress was ameliorated by quercetin. Quercetin supports the antioxidant defense mechanism and it is beneficial for treating fetal liver damage caused by ciprofloxacin.     

Enhanced testicular antioxidant capacity in streptozotocin-induced diabetic rats: protective role of vitamins C and E and selenium

Diabetes mellitus is associated with diabetic impairment of testicular function, ultimately leading to reduced fertility. Its etiology may involve oxidative damage by reactive oxygen substances, and protection against this damage can be offered by antioxidant supplementation. The aim of this study was to investigate the effects of intraperitoneal administration of vitamin C and E, selenium (Se), and vitamin E plus Se (COM) on concentrations of lipid peroxide (as malondialdehyde; MDA), reduced glutathione (GSH), and vitamin E concentrations and glutathione peroxidase (GSH-Px) activity in the testes of rats with diabetes induced by streptozotocin (STZ). Sixty groups were used (10 animals each) and these animals were initially allocated to two groups: control group and diabetic group. The diabetic group was subdivided into five groups as follows: diabetic control (DC), vitamin E, Se, COM, and vitamin C. Animals in the DC group and vitamin C, vitamin E, Se, and COM groups were made diabetic by the injection of STZ on 4 d after an injection of vitamins C and E, Se, and COM. Those vitamins and Se were also administered for 21 consecutive days. The MDA, vitamin E, GSH levels, and GSH-Px activities in testes were determined. Although the vitamin E concentration was higher in the control than in the DC group, the MDA levels were found to be lower in the control than in the DC group. The MDA levels in the testes samples of vitamin C, vitamin E, Se, and COM groups were lower than the DC group. However, GSH-Px activity and GSH levels in the testes were not significantly different between the control and DC groups. Vitamin E concentrations in the vitamin C, vitamin E, Se, and COM groups and GSH levels and GSH-Px activities in the Se, COM, and vitamin C groups were higher than either the control or DC group. The results indicate that reactive oxygen substances may be involved in possible testicular complications in diabetes of rats. Administration of vitamins C and E and Se reduced the testicular lipid peroxidation; these vitamins and Se had significant protective effects on testes of rats against oxidative damage in diabetes.     

The role of prednisolone and epinephrine on gastric tissue and erythrocyte antioxidant status in adrenalectomized rats.

It has been believed that overproduction of free radicals and/or deficiency of antioxidant systems, and stress hormones may play a role in etiopathogenesis of many diseases, including gastric ulcer. This study evaluated whether there was an effect of adrenalectomy on lipid peroxidation [malondialdehyde (MDA)] and antioxidant [superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione (GSH) levels] systems in gastric tissue and erythrocyte in rats. As well, the impacts of administration of prednisolone and epinephrine on these systems in adrenalectomized rats were investigated. Thirty-three rats were randomly grouped as sham-operated (group I), adrenalectomized (group II), adrenalectomized + prednisolone (group III) and adrenalectomized + epinephrine (group IV). After experimental procedures, blood and gastric tissues samples were taken from each animal in all groups. Colorimetric assays were employed to determine gastric tissue and erythrocyte levels of MDA and GSH, and SOD and GPX activities. Adrenalectomy in group II rats caused a marked decrease of SOD and GPX activities and MDA levels, and an increase of GSH levels in gastric tissue and erythrocyte, when compared to sham-operated rats. However, especially epinephrine injection after adrenalectomy resulted in a significantly increase of measured antioxidant enzyme activities and GSH levels in both gastric tissue and erythrocyte. These results indicate that adrenalectomy appeared to alter the levels of antioxidants and lipid peroxidation product in gastric tissue and erythrocyte. Thus, the present study provides a physiological regulatory role of adrenal gland in the maintenance of oxidant/antioxidant balance in gastric tissue and erythrocyte.     

The potential antioxidant effect of raloxifene treatment: a study on heart, liver and brain cortex of ovariectomized female rats

The antioxidant activity of some compounds buffer the free radicals generated either endogenously or exogenously, thus decreasing the potential damage mediated by oxidation. Recent studies documented that raloxifene has antioxidant properties in vitro. However, there are limited animal studies available to show raloxifene's antioxidant properties. We aimed to investigate the effects of raloxifene on antioxidant enzymes such as SOD, CAT and GPX, TrxR and the levels of GSH and MDA in heart, liver and brain cortex of ovariectomized female rats. Female Sprague Dawley rats weighing 300-350 g (n=24) were divided into three groups: (I) Eight non-ovariectomized rats were used as naive controls without any treatment (non-ovariectomized group, n=8). Five weeks after ovariectomy, (II) Ovariectomized placebo group (n=8) was given physiological saline, and (III) Raloxifene group (n=8) was given raloxifene 1 mg/kg sc. daily for 12 days. Ovariectomy induced significant increases on SOD, GPX, CAT activity and MDA levels in brain, heart and liver tissues compared to non-ovariectomized rats ( p<0.05). Raloxifene treatment led to decreased levels of SOD activity in heart, GPX activity in brain and CAT activity in liver tissue when compared to ovariectomized group ( p<0.05) but there was no change in activity of TrxR in all groups. The levels of MDA in brain, heart and liver tissues increased in ovariectomized group when compared to non-ovariectomized rats ( p<0.05). Raloxifene had a significant attenuating effect on the levels of MDA in brain and heart tissues. Our results also indicate that the levels of GSH in brain, heart and liver tissue decreased when compared to non-ovariectomized rats. Raloxifene treatment was observed to significantly increase the levels of GSH in brain and heart tissues ( p<0.05). However, there were insignificant differences for the GSH levels in liver tissues of ovariectomized placebo or raloxifene groups. In conclusion, our results demonstrate that raloxifene may be more effective against oxidative stress in heart and brain than in liver tissue.     

Effects of xylene and formaldehyde inhalations on oxidative stress in adult and developing rats livers.

In this study, it was aimed to demonstrate the possible oxidative stress caused by exposure of xylene and formaldehyde (HCHO) on liver tissue, and on body and liver weights in adult as well as developing rats. The rats (96 female Sprague-Dawley) were randomly divided into four groups: embryonic day 1 (Group 1), 1-day-old infantile rats (Group 2), 4-week-old rats (Group 3) and adult rats (Group 4). The animals were exposed to gases of technical xylene (300 ppm), HCHO (6 ppm) or technical xylene + HCHO (150 ppm + 3 ppm), 8 hours per day for 6 weeks. Superoxide dismutase (SOD) and catalase (CAT) activities, and glutathione (GSH) and malondialdehyde (MDA) levels were evaluated. In addition, body and liver weights were determinated. Compared to the control animals, body and liver weights were decreased in the embryonic day 1 group (P < 0.001, P < 0.01, respectively) and the 1-day-old infantile group (P < 0.001). Liver weight was increased in the 4-week-old group (P < 0.01). SOD activities were decreased in the 4-week-old rats exposed to HCHO (P < 0.01). CAT activities increased in the embryonic day 1 group (P < 0.05). GSH levels were decreased in the 1-day-old infantile group (P < 0.01), and MDA levels was increased in the embryonic day 1 group (P < 0.05) as compared with the respective control groups. As to GSH and MDA levels in adult and 4-week-old animals, no statistically significant differences were observed (P > 0.05). The present study indicates that exposures to xylene, HCHO and a mixture of them are toxic to liver tissue, and developing female rats are especially more adversely affected. Furthermore, the results of this study show that adult female rats could better tolerate the adverse effects of these toxic gases.     

Effect of melatonin on oxidative status of rat brain, liver and kidney tissues under constant light exposure

An enormous amount of data has been published in recent years demonstrating melatonin's defensive role against toxic free radicals. In the present study, we examined the role of melatonin as an antioxidant against the effect of continuous light exposure. Rats were divided into three groups. Control rats (group A) were kept under natural conditions whereas other group of rats (group B and C) were exposed to constant light for inhibition of melatonin secretion by the pineal gland. Group C rats also received melatonin via s.c. injection (1 mg x kg(- 1) body weight x day(- 1)). At the end of experiment, all animals were sacrificied by decapitation, serum and tissue samples were removed for determination of malondialdehyde (MDA), a product of lipid peroxidation, conjugated dienes levels and glutathione peroxidase (GSH-Px) activity levels. It was found that lipid peroxidation was increased in the rats which were exposed to constant light. Melatonin injection caused a decrease in lipid peroxidation, especially in the brain. In addition, melatonin application resulted in increased GSH-Px activity, which has an antioxidant effect. Thus, melatonin is not only a direct scavenger of toxic radicals, but also stimulates the antioxidative enzyme GSH-Px activity to detoxify hydroxyl radical produced by constant light exposure.     

Enhanced testicular antioxidant capacity in streptozotocin-induced diabetic rats

Diabetes mellitus is associated with diabetic impairment of testicular function, ultimately leading to reduced fertility. Its etiology may involve oxidative damage by reactive oxygen substances, and protection against this damage can be offered by antioxidant supplementation. The aim of this study was to investigate the effects of intraperitoneal administration of vitamin C and E, selenium (Se), and vitamin E plus Se (COM) on concentrations of lipid peroxide (as malondialdehyde; MDA), reduced glutathione (GSH), and vitamin E concentrations and glutathione peroxidase (GSH-Px) activity in the testes of rats with diabetes induced by streptozotocin (STZ). Sixty groups were used (10 animals each) and these animals were initially allocated to two groups: control group and diabetic group. The diabetic group was subdivided into five groups as follows: diabetic control (DC), vitamin E, Se, COM, and vitamin C. Animals in the DC group and vitamin C, vitamin E, Se, and COM groups were made diabetic by the injection of STZ on 4 d after an injection of vitamins C and E, Se, and COM. Those vitamins and Se were also administered for 21 consecutive days. The MDA, vitamin E, GSH levels, and GSH-Px activities in testes were determined. Although the vitamin E concentration was higher in the control than in the DC group, the MDA levels were found to be lower in the control than in the DC group. The MDA levels in the testes samples of vitamin C, vitamin E, Se, and COM groups were lower than the DC group. However, GSH-Px activity and GSH levels in the testes were not significantly different between the control and DC groups. Vitamin E concentrations in the vitamin C, vitamin E, Se, and COM groups and GSH levels and GSH-Px activities in the Se, COM, and vitamin C groups were higher than either the control or DC group. The results indicate that reactive oxygen substances may be involved in possible testicular complications in diabetes of rats. Administration of vitamins C and E and Se reduced the testicular lipid peroxidation; these vitamins and Se had significant protective effects on testes of rats against oxidative damage in diabetes. Abstract of the study was presented at the conference Trace Elements in Men and Animals-11. June 2–6, 2002; Dr. Naziroğlu has been awarded a TEMA11 Investigative Scientist Award.     

Age-related changes in antioxidant defence mechanisms and peroxidation in isolated hepatocytes from spontaneously hypertensive and normotensive rats

The effects of age and hypertension on the antioxidant defence systems and the lipid peroxidation in rat isolated hepatocytes were studied. Four different age groups (1,3,6 and 12 months) were considered in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Age-associated changes were observed on vitamin E status, glutathione (GSH) level, MDA formation and glutathione peroxidase (GSH-Px) activity in both strains. Maximal levels or activities of these parameters were found at 3 and 6 months, except for MDA which was low at 3 months. Then, a fall was observed at 12-month-old compared to 6-month values. In addition, GSH-Px activity was significantly lower in SHR than in WKY rats, except at the age of one month. The decrease of this enzyme activity could induce an increased cellular generation of radical species and lipid peroxidation, which might be link to hypertension.     

Protective effect of caffeic acid phenethyl ester (CAPE) on lipid peroxidation and antioxidant enzymes in diabetic rat liver

The aim of this study was to examine the effect of caffeic acid phenethyl ester (CAPE) on lipid peroxidation (LPO) and the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in the liver of streptozotocin (STZ)-induced diabetic rats. Twenty-seven rats were randomly divided into three groups: group I, control non-diabetic rats (n = 9); group II, STZ-induced, untreated diabetic rats (n = 8); group III, STZ-induced, CAPE-treated diabetic rats (n = 10), which were intraperitoneally injected with CAPE (10 microM kg(-1) day(-1)) after 3 days followed by STZ treatment. The liver was excised after 8 weeks of CAPE treatment, the levels of malondialdehyde (MDA) and the activities of SOD, CAT, and GSH-Px in the hepatic tissues of all groups were analyzed. In the untreated diabetic rats, MDA markedly increased in the hepatic tissue compared with the control rats (p < 0.0001). However, MDA levels were reduced to the control level by CAPE. The activities of SOD, CAT, and GSH-Px in the untreated diabetic group were higher than that in the control group (p < 0.0001). The activities of SOD and GSH-Px in the CAPE-treated diabetic group were higher than that in the control group (respectively, p < 0.0001, p < 0.035). There were no significant differences in the activity of CAT between the rats of CAPE-treated diabetic and control groups. Rats in the CAPE-treated diabetic group had reduced activities of SOD and CAT in comparison with the rats of untreated diabetic group (p < 0.0001). There were no significant differences in the activity of GSH-Px between the rats of untreated diabetic and CAPE-treated groups. It is likely that STZ-induced diabetes caused liver damage. In addition, LPO may be one of the molecular mechanisms involved in STZ-induced diabetic damage. CAPE can reduce LPO caused by STZ-induced diabetes.     

Melatonin controls oxidative stress and modulates iron, ferritin, and transferrin levels in adriamycin treated rats

AIM: Chemotherapy with adriamycin (ADR) is limited by its iron-mediated pro-oxidant toxicity. Because melatonin (MLT) is a broad spectrum antioxidant, we investigated the ability of MLT to control iron, its binding proteins, and the oxidative damage induced by ADR. MAIN METHODS: ADR was given as single i.p. dose of 10 mg kg(-1) body weight into male rats. MLT at a dose of 15 mg kg(-1) was injected daily for 5 days before ADR treatment followed by another injection for 5 days. Biochemical methods were used for this investigation. KEY FINDINGS: ADR injection caused elevations in plasma creatine kinase isoenzyme, lactic dehydrogenase, and aminotransferases, iron, ferritin, and transferrin. These changes were associated with increases in lipid peroxidation and protein oxidation as well as decreases in glutathione (GSH) levels and glutathione-S-transferase (GST) activity, while glutathione peroxidase (GSH-Px), and catalase (CAT) activity were elevated in the heart and liver of ADR treated rats. In the MLT+ADR group, the cardiac and hepatic function parameters and the levels of iron, transferrin and ferritin in plasma were normalized to control levels. The rats that were subjected to MLT+ADR had normalized CAT and GSH-Px activity and decreased TBARS and protein carbonyl levels compared the group only treated with ADR. GST activity and GSH concentration in the heart and liver were normalized when MLT accompanied ADR treatment. SIGNIFICANCE: MLT ameliorated oxidative stress by controlling iron, and binding protein levels in ADR treated rats demonstrating the usefulness of adriamycin in cancer chemotherapy and allowing a better management of iron levels.     

Zinc,ethanol, and lipid peroxidation in adult and fetal rats

Studies were performed on adult and fetal rats receiving either a zinc-deficient (<0.5 ppm) diet and/or ethanol (20%) throughout pregnancy. Liver zinc levels were depressed in fetuses exposed toin utero zinc deficiency, but brain zinc levels were unchanged. Ethanol had no effect on the concentration of zinc in the several fetal and adult tissues studies. Lipid peroxidation, as measured by endogenous levels of malondialdehyde (MDA) increased following food restriction, zinc improverishment, and alcoholism in adult and fetal livers, but not in fetal brains. Generally, levels of MDA were highest when both zinc deficiency and the ingestion of alcohol occurred concurrently. Glutathione (GSH) was depressed by zinc restriction in several adult and fetal tissues, but not in the fetal brain. Ethanol alone had no effect on GSH levels. The activity of the enzyme glutathione peroxidase (GSH-Px) was not changed in either organism by alcohol or zinc deficiency. Overall, the data point to increased lipid peroxidation in maternal and fetal rat tissues following zinc depletion and/or treatment with alcohol and draw attention to the apparent vulnerability of the fetal liver toin utero alcoholism. By contrast, the fetal brain seems to be especially resistant to alcohol and zinc-related lipoperoxidation. An association is suggested between the increased lipoperoxidation accompanying zinc deficiency and reduced levels of GSH, but this does not appear to relate to changes in the activity of GSH-Px. A similar relationship is not evident with respect to the increased levels of MDA in fetal and adult livers following chronic alcohol intoxication. A possible basis for the zinc-GSH interaction is discussed.     

Food restriction suppresses muscle growth and augments osteopenia in ovariectomized rats.

We examined effects of 4 wk of food restriction on ovariectomy-related changes in muscle, bone, and plasma insulin-like growth factor I (IGF-I). Female Sprague-Dawley rats (7 mo old) were assigned to freely eating groups: sham-operated (Sham), ovariectomized (Ovx-AL), and estrogen (estradiol)-replaced Ovx (Ovx+E(2)). Ovx rats were also pair fed with Sham (Ovx-PF) or weight matched with Sham by food restriction (Ovx-FR). Ovx-AL and Ovx-PF rats had similar estrogen status and body weight; therefore, the groups were combined (group: Ovx). After treatment, body weight was approximately 10% greater in Ovx than in Sham rats (P < 0.05), and muscle weight-to-body weight ratios were comparable among all groups. Bone mineral contents of whole tibiae in Ovx-FR and Ovx were approximately 15% (P < 0.05) and approximately 6% lower than in Sham rats (P < 0.05), respectively. Plasma IGF-I was approximately 30% higher in Ovx than in Sham (P < 0.05) but was similar between Sham and Ovx-FR. IGF-I was highly correlated with body weight and muscle mass. Within non-estrogen-replaced Ovx rats, IGF-I explained approximately 19% of variance in bone mineral content after accounting for variance attributable to body weight. Findings suggest that estrogen acts indirectly on skeletal muscle and bone in rats through regulation of body growth by factors such as IGF-I.