Maternal and developmental toxicity induced by Nanoalumina administration in albino rats and the potential preventive role of the pumpkin seed oil

Although Nanoalumina is widely used in many biomedical applications, its potential toxic effect on pregnant women and developing embryos/fetuses has not been reported. In this investigation, the maternal and developmental toxicity caused by Nanoalumina during gestation and the potential preventive role of the pumpkin seed oil (PSO) were evaluated. Four groups of pregnant rats were orally administered during days 5–19 of gestation as follows: control group, Nanoalumina group (70 mg/kg b.w), PSO- group (4 ml/kg b.w.), and Nanoalumina plus PSO- group. Nanoalumina induced detrimental impacts in pregnancy outcomes, fetal growth retardation, morphological anomalies, hepatic and neural DNA damage, and histopathological changes in hepatic and neural tissues of both mother and fetus, respectively. Furthermore, the level of MDA is significantly increased and activities of GSH and CAT are significantly reduced in both tissues of nanoalumina‐administered rats. PSO co administration improved pregnancy outcomes, fetal growth parameters, DNA damage, antioxidant defenses the histopathological changes of nanoalumina‐gavaged rats and significantly diminished MDA level. Finally, PSO has a preventive role against the detrimental impacts of nanoalumina in dams and fetuses probably via its potential to prevent reactive oxygen species.     

Carnosine and taurine treatments decreased oxidative stress and tissue damage induced by d-galactose in rat liver

d-galactose (GAL) causes aging-related changes and oxidative stress in the organism. We investigated the effect of carnosine (CAR) or taurine (TAU), having antioxidant effects, on hepatic injury and oxidative stress in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days/week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days/week) or TAU (2.5 % w/w; in rat chow) for 2 months. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and hepatic malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-0050x), and glutathione transferase (GST) activities were determined. Hepatic expressions of B cell lymphoma-2 (Bcl-2), Bax and Ki-67 were evaluated. Serum ALT, AST, hepatic MDA, and PC levels were observed to increase in GAL-treated rats. Hepatic Bax expression, but not Bcl-2, increased, Ki-67 expression decreased. GAL treatment caused decreases in GSH levels, SOD and GSH-Px activities in the liver. Hepatic mRNA expressions of SOD, but not GSH-Px, also diminished. CAR or TAU treatments caused significant decreases in serum ALT and AST activities. These treatments decreased apoptosis and increased proliferation and ameliorated histopathological findings in the livers of GAL-treated rats. Both CAR and TAU reduced MDA and PC levels and elevated GSH levels, SOD and GSH-Px (non significant in TAU?+?GAL group) activities. These treatments did not alter hepatic mRNA expressions of SOD and GSH-Px enzymes. Our results indicate that CAR and TAU restored liver prooxidant status together with histopathological amelioration in GAL-induced liver damage.     

Induction of oxidative stress and DNA damage in cervix in acute treatment with benzo[a]pyrene

Benzo[a]pyrene [B(a)P] is one of the most prevalent environmental carcinogens and genotoxic agents. However, the mechanisms of B(a)P-induced oxidative damage in cervical tissue are still not clear. The present study was to investigate the oxidative stress and DNA damage in cervix of ICR female mice induced by acute treatment with B(a)P. Oxidative stress was assayed by analysis of malondialdehyde (MDA), superoxide anion and H(2)O(2), and antioxidant enzymes. The alkaline single-cell electrophoresis (SCGE) was used to measure DNA damage. The contents of MDA and glutathione (GSH), and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were significantly increased in cervix 24, 48 and 72h after B(a)P treatment of a single dose of 12.5 and 25mg/kg, while GSH, CAT, SOD and GST had no significant difference with the dose of 50mg/kg B(a)P at post-treatment time 48 and 72h except for SOD activity at 48h which was significant. The maximum values of SOD, CAT, GST and GSH were peaked at 24h and then decreased gradually while GPx activities and MDA levels persisted for up to 72h. Superoxide anion, H(2)O(2) and DNA damage changed similarly as the activity of SOD, CAT or GST. Additionally, increases of formamidopyrimidine DNA glycosylase (FPG) specific DNA damage were observed and can be greatly rescued by vitamin C pretreatment. Overall, B(a)P demonstrated a time- and dose- related oxidative stress and DNA damage in cervix.     

Garlic and vitamin E provides antioxidant defence in tissues of female rats treated with nicotine

Nicotine is known to induce oxidative stress in rat tissues and the antioxidant properties of garlic have been reported. This study was designed to determine if the peroxidative damage caused by nicotine administration can be effectively prevented with garlic juice, and vitamin E, a known antioxidant.Four groups of six rats each were divided into: Group I: (control) received 0.2ml of 0.9% normal saline, group II (received nicotine 0.6mg/kg b.w subcutaneously), group III (received nicotine 0.6mg/kg b.w + garlic juice 100mg/kg b.w orally), and group IV (received nicotine 0.6mg/kg b.w + Vitamin E 100mg/kg b.w orally). All animals were treated for 21 days. The pituitary gland, ovary, uterus, heart, liver and kidney of the animals were harvested, weighed and homogenized. Malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione (GSH) were then measured.Concentration of MDA was significantly increased in tissues of nicotine treated rats when compared with the control. In group III and IV, MDA levels were significantly reduced when compared with nicotine group. The activities of SOD and GSH significantly decreased in group II (nicotine only) rat tissues, while it was significantly increased in group III and IV rat tissues. The study showed that garlic juice extract (100mg/kg b.w) and vitamin E (100mg/kg b.w) administration prevented oxidative damage in rat tissues treated with nicotine. The study also showed that vitamin E has a more potent antioxidant activity than garlic juice in preventing nicotine induced oxidative damage in rat. Keywords: Nicotine, Vitamin E, Garlic, antioxidant.     

Antioxidant levels in blood and seminal plasma and their impact on sperm parameters in infertile men

Excess reactive oxygen species (ROS) beyond the scavenging capacity of antioxidants leads to DNA damage and oxidation of lipoprotein components at the cellular and subcellular level. The oxidative stress (OS) adversely affects sperm function by altering membrane fluidity, permeability and impairs sperm functional competence. In the present study, the OS status in seminal plasma and blood serum in infertile men and its relationship with spermatozoa parameters have been investigated. Four groups of infertile men viz., oligozoospermic (n = 15), asthenozoospermic (n = 17), teratozoospermic (n = 19), and oligoasthenoteratozoospermic (n = 9), and healthy fertile controls (n = 40) have been analyzed for superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA) in seminal plasma and blood serum. Significant correlation between blood serum SOD and sperm count has been observed in patients (p = 0.018) and controls (p = 0.021). Similarly, significant correlation between blood serum GSH and sperm progressive motility in patients (p = 0.036) and controls (p = 0.029) is observed. The low seminal MDA is associated with increase in sperm progressive motility in patients (p = 0.039) and controls (p = 0.028). Positive correlation is found between increased seminal MDA levels and abnormal sperm morphology in both patients and controls (r = 0.523, p = 0.029; r = 0.612, p = 0.034 respectively). Correlations between blood SOD and sperm count and between blood GSH levels and progressive motility suggest that these can be important biochemical markers in assaying the sperm count and motility. A negative correlation of motility with seminal MDA indicates that sperm membrane lipid peroxidation affects the fluidity and thus mobility of sperm axoneme. This affects functional competence of the sperm and acts like a biological safeguard. The results of the present study suggest the prospects of using the blood serum and seminal plasma antioxidants as a valuable tool to evaluate the sperm reproductive capacity and functional competence.     

Protective effect of silymarin on oxidative stress in rat brain

Brain is susceptible to oxidative stress and it is associated with age-related brain dysfunction. Previously, we have pointed out a dramatic decrease of glutathione levels in the rat brain after acetaminophen (APAP) oral administration overdose. Silymarin (SM) is a mixture of bioactive flavonolignans isolated from Silybum marianum (L.) Gaertn., employed usually in the treatment of alcoholic liver disease and as anti-hepatotoxic agent in humans. In this study, we have evaluated the effect of SM on enzymatic and non enzymatic antioxidant defensive systems in rat brain after APAP-induced damage. Male albino Wistar rats were treated with SM (200 mg/kg/die orally) for three days, or with APAP single oral administration (3 g/kg) or with SM (200 mg/kg/die orally) for 3 days and APAP single oral administration (3 g/kg) at third day. Successively the following parameters were measured: reduced and oxidized glutathione (GSH and GSSG), ascorbic acid (AA), enzymatic activity variations of superoxide dismutase (SOD) and malondialdehyde levels (MDA). Our results showed a significant decrease of GSH levels, AA levels and SOD activity and an increase of MDA and GSSG levels after APAP administration. After SM administration GSH and AA significantly increase and SOD activity was significantly enhanced. In the SM+APAP group, GSH values significantly increase and the others parameters remained unchanged respect to control values. These results suggest that SM may to protect the SNC by oxidative damage for its ability to prevent lipid peroxidation and replenishing the GSH levels.     

Palm tocotrienol-rich fraction reduced plasma homocysteine and heart oxidative stress in rats fed with a high-methionine diet

Oxidative stress contributes to cardiovascular diseases. We aimed to study the effects of palm tocotrienol-rich fraction (TRF) on plasma homocysteine and cardiac oxidative stress in rats fed with a high-methionine diet. Forty-two male Wistar rats were divided into six groups. The first group was the control. Groups 2–6 were fed 1 % methionine diet for 10 weeks. From week 6 onward, folate (8 mg/kg diet) or palm TRF (30, 60 and 150 mg/kg diet) was added into the diet of groups 3, 4, 5 and 6. The rats were then killed. Palm TRF at 150 mg/kg and folate supplementation prevented the increase in plasma total homocysteine (4.14?±?0.33 and 4.30?±?0.26 vs 5.49?±?0.25 mmol/L, p?<?0.05) induced by a high-methionine diet. The increased heart thiobarbituric acid reactive substance in rats fed with high-methionine diet was also prevented by the supplementations of palm TRF (60 and 150 mg/kg) and folate. The high-methionine group had a lower glutathione peroxidase activity (49?±?3 vs 69?±?4 pmol/mg protein/min) than the control group. This reduction was reversed by palm TRF at 60 and 150 mg/kg diet (p?<?0.05), but not by folate. Catalase and superoxide dismutase activities were unaffected by both methionine and vitamin supplementations. In conclusion, palm TRF was comparable to folate in reducing high-methionine diet-induced hyperhomocysteinemia and oxidative stress in the rats’ hearts. However, palm TRF was more effective than folate in preserving the heart glutathione peroxidase enzyme activity.     

Effects of boric acid feeding on the oxidative stress parameters in testes,sperm parameters and DNA damage in mice

This study was aimed to determine the effects of boric acid on oxidative stress, testicular tissue and spermatozoon DNA. Experiments were performed with Swiss Albino mice divided equally into two groups based on the tratment period: one for 4 and the other for 6-week duration. These groups were further divided into subgroups as Control and those administered daily at oral doses of 115 mg/kg, 250 mg/kg and 450 mg/kg of boric acid. Then, testicular tissue were examined postmortem and analyzed using ex-vivo biochemical tools for oxidative stress, spermatozoon membrane integrity, sperm motility and live cell rate (%). In both 4 and 6-week groups, v. seminalis weight, membrane integrity, motility, live cells and GSH levels exhibited a decreasing trent compared to the controls. In addition, 6-week group had a decrease in SOD level. MDA level was higher in controls in both 4 and 6-week groups. Spermatozoon DNA was intact in the 4-week group, but damaged in the 6-week group, and the degree of the damage dependent on the administered dose. Boric acid induces oxidative stress in testicular tissue, and its long-term application (only 6 weeks) caused damage in spermatozoon DNA.     

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.     

Effects of Flaxseed Oil on Lead Acetate-Induced Neurotoxicity in Rats

It is well known that chronic exposure to lead (Pb(+2)) alters a variety of behavioral tasks in rats and mice. Here, we investigated the effect of flaxseed oil (1,000?mg/kg) on lead acetate (20?mg/kg)-induced brain oxidative stress and neurotoxicity in rats. The levels of Pb(+2), lipid peroxidation, nitric oxide (NO), and reduced glutathione (GSH) and the activity of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione-S-transferase (GST), and glutathione peroxidase (GPx) were determined in adult male albino rats. The level of Pb(+2) was markedly elevated in brain and blood of rats. This leads to enhancement of lipid peroxidation and NO production in brain with concomitant reduction in GSH, CAT, SOD, GR, GST, and GPx activities. These findings were associated with DNA fragmentation. In addition, lead acetate induced brain injury as indicated by histopathological changes of the brain. Treatment of rats with flaxseed oil resulted in marked improvement in most of the studied parameters as well as histopathological features. These findings suggest to the conclusion that flaxseed oil significantly decreased the adverse harmful effects of lead acetate exposure on the brain as well as Pb(+2)-induced oxidative stress.     

Protective effects of garlic oil on hepatocarcinoma induced by N-nitrosodiethylamine in rats

To investigate the protective effects and the possible mechanisms of garlic oil (GO) against N-nitrosodiethylamine (NDEA)-induced hepatocarcinoma in rats, Wistar rats were gavaged with GO (20 or 40 mg/kg) for 1 week, and then were gavaged with GO and NDEA (10 mg/kg) for the next 20 weeks. The changes of morphology, histology, the biochemical indices of serum, and DNA oxidative damage of liver were examined to assess the protective effects. Lipid peroxidation (LPO), antioxidant defense system, and apoptosis-related proteins were measured to investigate potential mechanisms. At the end of the study (21 weeks), GO administration significantly inhibited the increase of the nodule incidence and average nodule number per nodule-bearing liver induced by NDEA, improved hepatocellular architecture, and dramatically inhibited NDEA-induced elevation of serum biochemical indices (alanine aminotransferase , aspartate aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase) and hepatic 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in a dose-dependent manner. The mechanistic studies demonstrated that GO counteracted NDEA-induced oxidative stress in rats illustrated by the restoration of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST) levels, and the reduction of the malondialdehyde (MDA) levels in liver. Furthermore, the mRNA and protein levels of Bcl-2, Bcl-xl, andβ-arrestin-2 were significantly decreased whereas those of Bax and caspase-3 were significantly increased. These data suggest that GO exhibited significant protection against NDEA-induced hepatocarcinogenesis, which might be related with the enhancement of the antioxidant activity and the induction of apoptosis.     

Melatonin and vitamin C administration ameliorate diazepam-induced oxidative stress and cell proliferation in the liver of rats

Abstract.  Objective : Oxidative stress is a likely molecular mechanism in long-term diazepam administration. The benefits of antioxidants (melatonin and vitamin C) against diazepam-induced cell proliferation, DNA synthesis and oxidative damage were investigated in this study. Materials & methods : Four equal-sized groups of male rats [control, diazepam (3 mg/kg), diazepam plus melatonin (5 mg/kg) and diazepam plus vitamin C (50 mg/kg)] were used. Levels of lipid peroxides (LPO), superoxide dismutase (SOD) activity and glutathione (GSH) concentration were measured in tissue homogenates. Cell proliferation and rate of DNA synthesis were detected by autoradiography. Results : Results documented increased labelling index, ³H-thymidine incorporation (DNA synthesis), LPO plus decrease in GSH levels and SOD activity in livers of diazepam-administered rats versus those of controls. When melatonin and vitamin C were given to diazepam-administered rats, they almost attenuated the increase of labelling index, DNA synthesis and LPO, and restored the levels of GSH and SOD activity. Conclusion : These results suggest long-term hazard in use of drugs such as diazepam; they may be toxic and damage terminates in complex liver damage. Furthermore, melatonin and vitamin C may be useful in combating free radical-induced liver injury resulting from hazard and/or repeated diazepam administration.     

The effects of dietary boric acid and borax supplementation on lipid peroxidation,antioxidant activity,and DNA damage in rats

The aims of this study were to clarify the effects of high dietary supplementation with boric acid and borax, called boron (B) compounds, on lipid peroxidation (LPO), antioxidant activity, some vitamin levels, and DNA damage in rats. Thirty Sprague Dawley male rats were divided into three equal groups: the animals in the first group (control) were fed with a standard rodent diet containing 6.4 mg B/kg, and the animals in the experimental group were fed with a standard rodent diet added with a supra-nutritional amount of boric acid and borax (100 mg B/kg) throughout the experimental period of 28 days. The B compounds decreased malondialdehyde (MDA), DNA damage, the protein carbonyl content (PCO) level in blood, and glutathione (GSH) concentration in the liver, Cu–Zn superoxide dismutase (SOD), and catalase (CAT) activity in the kidney. The B compounds increased GSH concentration in blood and the vitamin C level in plasma. Consequently, our results demonstrate that B supplementation (100 mg/kg) in diet decreases LPO, and enhances the antioxidant defense mechanism and vitamin status. There are no differences in oxidant/antioxidant balance and biochemical parameters except for serum vitamin A and liver GSH concentration, between the boron compounds used in this study.     

Effect of rosmarinic acid on inhibition of gentamicin induced nephrotoxicity in rats

The present investigation reports the effect of rosmarinic acid (RA), an antioxidant on gentamicin sulphate (GS)-induced renal oxidative damage in rats. Rosmarinic acid (RA) has been demonstrated to have antioxidant, free radical scavenger and anti-inflamatory effects. Twenty-eight Sprague-Dawley rats were divided in to four equal groups as follows: group 1 (control), group 2 (GS 100 mg/kg/d ip), group 3 (GS 100 mg/kg/d ip + RA 50 mg/kg/d) and group 4 (GS 100 mg/kg/d ip + RA 100 mg/kg/d). Treatments were administrated once daily for 12 days. After 12 days 24 h urine was collected, blood was sampled and kidneys were removed. Serum and kidney tissue MDA assessed by thiobarbituric acid. Kidney paraffin sections (5 μm thickness) from the left kidney stained with periodic acid Schiff. Tubular necrosis was studied semiquantitatively and glomerular volume and volume density of proximal convoluted tubule (PCT) estimated stereologically. Kidney homogenize were prepared from right kidney. Serum creatinine, urea and kidney antioxidant enzymes activity were assessed by special kits. Data were compared by SPSS 13 software and Mann–Whitney test at p < 0.05. Co treatment of GS and RA (High dose) significantly decreased serum creatinine, MDA, urea, tubular necrosis (p < 0.05) and increase renal GSH, GPX, CAT, SOD, volume density of PCT and creatinine clearance significantly in comparison with GS group (p < 0.05). Treatment with RA (high dose) maintained serum creatinine, volume density of PCT, renal GSH, GPX, SOD and MDA as the same level as control group significantly (p < 0.05). In conclusion, RA alleviates GS nephrotoxicity via antioxidant activity, increase of renal GSH content and increase of renal antioxidant enzymes activity.     

Cytoprotective effects of carvedilol against oxygen free radical generation in rat liver

The protective effects of carvedilol, an antihypertensive agent, against oxidative injury caused by acetaminophen were studied in rat liver. Male Wistar rats (250 +/- 30 g) were pre-treated with carvedilol (3.6 mg/kg, p.o.) for 10 days and on the 11th day received an overdose of acetaminophen (800 mg/kg, p.o.). Four hours after acetaminophen administration, blood was collected to determine serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). After that, rats were killed and the livers were excised to determine reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS) and carbonyl protein contents, and the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST), and also the DNA damage index. Acetaminophen significantly increased the levels of TBARS, the DNA damage and SOD, AST and ALT activities. Carvedilol was able to prevent lipid peroxidation, protein carbonilation and DNA fragmentation caused by acetaminophen. Moreover, this drug prevented increases in SOD, AST and ALT activities. These results show that carvedilol exerts cytoprotective effects against oxidative injury caused by acetaminophen in rat liver. These effects are probably related to the O2*- scavenging property of carvedilol or its metabolites.     

The effect of Myrtus communis L. ethanol extract on the small intestine and lungs in experimental thermal burn injury

Thermal trauma can damage organs away from the skin burn site and lead to multiple organ dysfunction. Following thermal injury, all tissues are exposed to ischemia, and as a result, resuscitation and reperfusion occur during the burning shock. Burn damage starts systemic inflammatory reactions that produce toxins and reactive oxygen radicals that lead to peroxidation. This study aimed to investigate, for the first time, the possible antioxidant effects of Myrtus communis ethanol extract on burn-induced oxidative distant organ injury orally. The thermal trauma was generated under ether anesthesia by exposing the dorsum of rats to 90 ^°C water bath for 10 s. 100 mg/kg/day Mrytus communis ethanol extract was applied orally for two days. Malondialdehyde (MDA) and glutathione (GSH) levels, glutatinone-S-transferase (GST), superoxidedismutase (SOD) and catalase (CAT) activities were determined to detect the possible antioxidant effects of myrtle on small intestine and lung tissues. Burn damage significantly increased MDA levels in lung and small intestine tissues, and significantly decreased GSH levels, CAT and GST activities in the small intestine and lung tissues compared to control group. Mrytus communis ethanol extract decreased MDA level and increased GSH level, SOD, CAT and GST activities significantly in either small intestine or lung tissues. Mrytus communis extract may be an ideal candidate to be used as an antioxidant adjunct to improve oxidative distant organ damage to limit the systemic inflammatory response and decreasing the recovery time after thermal injury.     

Protective effect of ellagic acid and pumpkin seed oil against methotrexate-induced small intestine damage in rats

Gastrointestinal toxicity is one of the most serious side effects in the methotrexate (MTX) treatment. This study was designed to investigate whether ellagic acid (EA) and/or pumpkin seed oil (PSO) had a protective effect on MTX-induced small intestine damage. Forty albino rats were randomized into five groups of 8 rats each. Group I served as a normal control group. In Group II, MTX was administered as a single dose (20 mg/kg) intraperitoneally. Groups III, IV and V were pre-treated respectively with either PSO (40 mg/kg), EA (10 mg/kg) or 0.2% DMSO (vehicle control) orally every day by gavage for 5 days and then they received MTX. All animals were sacrificed 5 days after the intraperitoneal injection of MTX for histopathological examination, estimation of serum prostaglandin E2 (PGE2) level, assay of tissue malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) levels and myloperoxidase (MPO), xanthine oxidase (XO) and adenosine deaminase (AD) activities. Administration of EA and/or PSO decreased the intestinal damage, PGE2, MDA and NO levels and MPO, XO and AD activities and increased GSH level. These results suggest that EA and PSO protect the small intestine of rats from MTX-induced damage through their antioxidant and anti-inflammatory effects and thus have potential as a promising drug in the prevention of undesired side effects of MTX.     

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 iloprost on visual evoked potentials and brain tissue oxidative stress after bilateral common carotid artery occlusion

Effects of iloprost on visual evoked potentials and oxidant/antioxidant status were evaluated after bilateral carotid artery occlusion. There were three experimental groups; Sham (S) group (n=10), bilateral common carotid artery occluded (BCCAO) group (n=10) and after bilateral common carotid artery occlusion, iloprost-treated (BCCAOI) group (n=10). Iloprost was administered (0.5ng/kg/day) for 10 days by intraperitoneal injection. N(2) and P(2) latencies (millisecond) and N(2)-P(2) (microV) amplitudes were recorded 10 days after operation for evaluating VEPs. The rats were sacrificed by decapitation immediately after recording of VEPs. Malondialdehyte (MDA), glutathione (GSH), Cu-Zn superoxide dysmutase (SOD) were studied spectrophotometricly. After BCCAO, MDA levels were increased, GSH and Cu-Zn SOD levels were decreased significantly, and abnormal VEPs parameters were observed. Iloprost treatment after BCCAO decreased MDA and increased GSH levels significantly. Low Cu-Zn SOD levels and impaired VEPs remained after iloprost treatment. Iloprost treatment may protect the brain tissue from oxidative damage during cerebral hypoperfusion.     

Cadmium-induced oxidative stress and DNA damage in kidney of pregnant female rats

In the present study, we have investigated the influence of sub-acute treatment with cadmium (Cd) on some parameters indicative of oxidative stress and DNA damage in tissues of pregnant female rats. Pregnant female rats (n=6) were injected subcutaneously, daily with a dose of cadmium chloride of 3 mg/kg body weight (b.w.) from day 6 to day 19 of pregnancy, and they were allowed to deliver normally. MDA level and GPx, CAT and SOD activities were used as markers of oxidative stress in liver and kidney. The 8-oxo-dG level was measured by the HPLC-EC system. Cd treatment increased MDA (+116%, p<0.01) in kidney. Moreover, Cd treatment also decreased CuZn-SOD (-11%, p<0.05) and GSH level (-52%, p<0.05) in kidney. Treated rats displayed an increase of the liver metallothionein (MT) level. Induction of MT in liver was probably implicated in the detoxification of Cd. The high level of Cd (3 mg/kg) used in the present study is partially neutralized by MT in liver, whereas the free fraction could be implicated in the oxidative stress and DNA oxidation observed in kidney. Cd treatment failed to alter 8-oxodGuo, indicating the absence of DNA oxidation in liver; by contrast, the same treatment increased the 8-oxodGuo level (+51%, p<0.05) in the kidney of pregnant female rats, indicating an oxidative stress associated with DNA damage only in kidney.