Heat stress-induced hepatotoxicity and its prevention by resveratrol in rats

The high ambient temperature beyond the range of comfort zone or thermoneutral zone causes environmental heat stress (HST). It causes serious physiological dysfunction that may result in heat-related diseases and even death. The underlying mechanism in the pathogenesis of hepatic dysfunction following hyperthermic challenge and the possible involvement of oxidative stress to induce oxidative deterioration of liver functions in adult rats are investigated in this study. Cellular damage was assessed in terms of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and histology of liver. The effect of hyperthermia in altering the oxidative stress was evaluated on the basis of its influence on hepatic lipid peroxidation and antioxidant status—superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity. The current study demonstrated that HST is associated with a complex set of integrated alterations in liver, time-dependent rise in oxidative stress followed by distinct pattern of liver injury in animals. Heat-induced hepatotoxicity was assessed by increased lipid peroxidation, depletion of antioxidant enzyme activities such as SOD, CAT, GPx and tissue damages revealed by hepatic vacuolization, and widespread necrosis. The study also revealed that pretreatment with resveratrol resulted in normalizing these parameters appreciably, emphasizing the therapeutic potentials of this polyphenol. Taken together, the results suggest that an increase in free radical formation relative to loss of the antioxidant defense system during heat stress may render liver more susceptible to oxidative damage, leading to their functional inactivation. However, resveratrol supplementation can be an effective antidote in the treatment of HST-induced malfunction.     

Comparative study of natural antioxidants - curcumin, resveratrol and melatonin - in cadmium-induced oxidative damage in mice

The present study was designed to examine the antioxidative effect of curcumin, resveratrol and melatonin pre-treatment on cadmium-induced oxidative damage and cadmium distribution in an experimental model in mice. Male CD mice were treated once daily for 3 days with curcumin (50mg/kg b.w., p.o.), resveratrol (20mg/kg b.w., p.o.) or melatonin (12mg/kg, p.o.), dispersed in 0.5% methylcellulose. One hour after the last dose of antioxidants cadmium chloride was administered (7mg/kg b.w., s.c.) to pre-treated animals and control animals receiving methylcellulose. At 24th h after Cd administration the lipid peroxidation (LP - expressed as malondialdehyde production), reduced glutathione (GSH), catalase (CAT) and glutathione peroxidase (GPx) were estimated in liver homogenates. Cadmium concentration was measured in the liver, kidneys, testes and brain by AAS. Cadmium chloride administration to mice induced hepatic lipid peroxidation (to 133%, p<0.001), decreased GSH content (to 65%, p<0.001) and inhibited catalase (to 68%, p<0.001) and GPx activity (to 60%, p<0.001) in the liver. Curcumin, resveratrol and melatonin oral pre-treatment completely prevented the Cd-induced lipid peroxidation and Cd-induced inhibition of GPx hepatic activity. Resveratrol was effective against Cd-induced inhibition of catalase activity (p<0.001). The decrease in hepatic GSH level was not prevented by curcumin, resveratrol or melatonin pre-treatment. In mice treated with antioxidants alone the level of LP, GSH, GPx or CAT was not different from control levels. The pre-treatment with antioxidants did not affect cadmium distribution in the tissues of Cd-intoxicated mice. The results demonstrate that curcumin, resveratrol and melatonin pre-treatment effectively protect against cadmium-induced lipid peroxidation and ameliorate the adverse effect of cadmium on antioxidant status without any reduction in tissue Cd burden.     

The preventive inhibition of chondroitin sulfate against the CCI<Subscript>4</Subscript>-lnduced oxidative stress of subcellular level

Our work in this study was made in the microsomal fraction to evaluate the lipid peroxidation by measuring superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) and to elucidate the preventive role of CS in the CCl4-induced oxidative stress. The excessive lipid peroxidation by free radicals derived from CCl4 leads to the condition of oxidative stress which results in the accumulation of MDA. MDA is one of the end-products in the lipid peroxidation process and oxidative stress. MDA, lipid peroxide, produced in this oxidative stress causes various diseases related to aging and hepatotoxicity, etc. Normal cells have a number of enzymatic and nonenzymatic endogenous defense systems to protect themselves from reactive species. The enzymes in the defense systems, for example, are SOD, CAT, and GPx. They quickly eliminate reactive oxygen species (ROS) such as superoxide anion free radical *O2(-), hydrogen peroxide H2O2 and hydroxyl free radical *OH. CS inhibited the accumulation of MDA and the deactivation of SOD, CAT and GPx in the dose-dependent and preventive manner. Our study suggests that CS might be a potential scavenger of free radicals in the oxidative stress originated from the lipid peroxidation of the liver cells of CCl4-treated rats.     

Hematological and Hepatic Effects of Ulexite in Zebrafish

The ulexite (UX), a borate mineral, is used as boron source and commonly used in various industrial processes. The hematological and hepatic effects of UX were investigated by exposing adult zebrafish to UX (5, 10, 20 and 40 mg/L) over 96 hours. The blood and liver tissues were taken at the end of the trial period then micronucleus (MN) rates, oxidative DNA damage (8-OHdG), apoptosis (Caspase-3), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), myeloperoxidase (MPO), paraoxonase (PON), arylesterase (AR) and lipid peroxidation (MDA) levels were determined. Genotoxic damage by UX occurred only at 40 mg/L in the blood MN assay. Oxidative stress, oxidative DNA damage and apoptosis in liver also occurred at this dose. Moreover, 5-20 mg/L doses led to decreases of DNA damage and apoptosis levels via promoting antioxidant system in liver tissues. UX exhibits beneficial roles on blood and liver tissues of zebrafish at relatively lower doses, which may be relevant to nutritional and medicinal industries.     

Acetaminophen increases the risk of arsenic‐mediated development of hepatic damage in rats by enhancing redox‐signaling mechanism

We evaluated whether the commonly used analgesic‐antipyretic drug acetaminophen can modify the arsenic‐induced hepatic oxidative stress and also whether withdrawal of acetaminophen administration during the course of long‐term arsenic exposure can increase susceptibility of liver to arsenic toxicity. Acetaminophen was co‐administered orally to rats for 3 days following 28 days of arsenic pre‐exposure (Phase‐I) and thereafter, acetaminophen was withdrawn, but arsenic exposure was continued for another 28 days (Phase‐II). Arsenic increased lipid peroxidation and reactive oxygen species (ROS) generation, depleted glutathione (GSH), and decreased superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione reductase (GR) activities. Acetaminophen caused exacerbation of arsenic‐mediated lipid peroxidation and ROS generation and further enhancement of serum alanine aminotransferase and aspartate aminotransferase activities. In Phase‐I, acetaminophen caused further GSH depletion and reduction in SOD, catalase, GPx and GR activities, but in Phase‐II, only GPx and GR activities were more affected. Arsenic did not alter basal and inducible nitric oxide synthase (iNOS)‐mediated NO production, but decreased constitutive NOS (cNOS)‐mediated NO release. Arsenic reduced expression of endothelial NOS (eNOS) and iNOS genes. Acetaminophen up‐regulated eNOS and iNOS expression and NO production in Phase‐I, but reversed these effects in Phase‐II. Results reveal that acetaminophen increased the risk of arsenic‐mediated hepatic oxidative damage. Withdrawal of acetaminophen administration also increased susceptibility of liver to hepatotoxicity. Both ROS and NO appeared to mediate lipid peroxidation in Phase‐I, whereas only ROS appeared responsible for peroxidative damage in Phase‐II. © 2011 Wiley Periodicals, Inc. Environ Toxicol 29: 187–198, 2014.     

Antidiabetic effect of Phlomis anisodonta: effects on hepatic cells lipid peroxidation and antioxidant enzymes in experimental diabetes.

The present study investigated the effects of aerial parts of Phlomis anisodonta methanolic extract (PAE) on streptozotocin (STZ)-induced diabetic rats by measuring fasting blood glucose, serum insulin, change in body weight, ferric reducing antioxidant power (FRAP), lipid peroxidation (LPO), and liver antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Male Wistar rats were randomly divided into six groups of six animals. Treatment of diabetic rats with oral administration of PAE at doses of 100, 200 and 400 mg kg(-1) for 10 days resulted in a significant reduction in fasting blood glucose, and an increase in serum insulin levels in comparison with diabetic control group. PAE also protected rats from STZ-induced loss in body weight. Hepatic FRAP increased and LPO in diabetic rats decreased after treatment by PAE at doses of 200 and 400 mg kg(-1). PAE-treated diabetic rats at three doses indicated a significant increase in hepatic SOD, CAT, and GPx activities. These results suggest that PAE is beneficial in the control of diabetes by reduction of blood glucose and increasing insulin levels and combating oxidative stress by activation of hepatic antioxidant enzymes.     

Comparative effects of curcumin and resveratrol on aflatoxin B1-induced liver injury in rats

Aflatoxin B₁ is a potent hepatotoxic and hepatocarcinogenic mycotoxin. Lipid peroxidation and oxidative DNA damage are the principal manifestations of aflatoxin B₁-induced toxicity that could be counteracted by antioxidants. Many plant constituents have been reported to prevent liver damage associated with lipid peroxidation. In this study, curcumin (polyphenolic antioxidant purified from turmeric) and resveratrol (polyphenol obtained from grapes) were evaluated for possible protection against liver injury induced by aflatoxin B₁ in rats. Adult male Fischer rats were divided into six groups including untreated control, curcumin control (200 mg/kg BW), resveratrol control (10 mg/kg BW) and aflatoxin B₁ (25 μg/kg BW). Other two groups were administered either curcumin or resveratrol along with aflatoxin B₁. The study was carried out for 90 days. At the end of the experiment period, blood and tissue samples were collected from the animals before they were killed. Livers were collected for histopathologic studies and fixed in 10% buffered formalin solution. Serum was used for estimation of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (γ-GT) enzymes. The lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were estimated in liver homogenates. The results revealed that aflatoxin B₁ administration caused liver damage as indicated by statistically significant (P < 0.05) increase in serum ALT, AST and γ-GT levels. In addition, there were general statistically significant reductions in the activities of GSH, SOD, CAT, GSH-Px, and an increase in lipid peroxidation in the liver of aflatoxin B₁-treated group compared to the untreated control group. Curcumin showed a significant hepatoprotective activity by lowering the levels of serum marker enzymes, lipid peroxidation and elevating the levels of GSH, SOD, CAT and GSH-Px. However, resveratrol failed to protect from the aflatoxin B₁-induced liver injury. These findings suggest that curcumin but not resveratrol has a hepatoprotective effect against aflatoxin B₁-induced liver injury.     

The role of vitamin C as antioxidant in protection of oxidative stress induced by imidacloprid

Pesticides may induce oxidative stress leading to generate free radicals and alternate antioxidant or oxygen free radical scavenging enzyme system. This study was conducted to investigate the acute toxicity of imidacloprid toward male mice and the oxidative stress of the sublethal dose (1/10 LD₅₀) on the lipid peroxidation level (LPO), reduced glutathione content (GSH) and activities of the antioxidant enzymes; catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glucose-6-phosphate dehydrogenase (G6PD), and glutathione-s-transferase (GST). Also, the protective effect of vitamin C (200 mg/kg bw) 30 min before or after administration of imidacloprid were investigated. The results demonstrated that the median lethal dose (LD₅₀) of imidacloprid after 24 h was 149.76 mg/kg bw. The oral administration of 14.976 mg/kg imidacloprid significantly caused elevation in LPO level and the activities of antioxidant enzymes including CAT, SOD, GPx and GST. However, G6PD activity remained unchanged, while the level of GSH content was decreased. In addition, the results showed that vitamin C might ameliorate imidacloprid-induced oxidative damage by decreasing LPO and altering antioxidant defense system in liver. The protective effect of the pre-treatment with vitamin C against imidacloprid-induced oxidative stress in liver mice is better than the post-treatment.     

Bacopa monnieri modulates antioxidant responses in brain and kidney of diabetic rats

Role of oxidative stress has been reported in various diabetic complications including neuropathy, nephropathy and cardiopathy. This study was undertaken to evaluate the protective effect of Bacopa monnieri, a medicinal plant, on tissue antioxidant defense system and lipid peroxidative status in streptozotocin-induced diabetic rats. Extract of B. monnieri was administered orally, once a day for 15 days (at doses 50, 125 and 250mg/(kgbw)) to diabetic rats. Activity of antioxidant enzymes (SOD, Catalase, and GPx), levels of GSH and lipid peroxidation were estimated in kidney, cerebrum, cerebellum and midbrain of diabetic rats and compared to reference drug, Glibenclamide. Administration of plant extract to diabetic rats showed significant reversal of disturbed antioxidant status and peroxidative damage. Significant increase in SOD, CAT, GPx activity and levels of GSH was observed in extract treated diabetic rats. The present study indicates that extract of B. monnieri modulates antioxidant activity, and enhances the defense against ROS generated damage in diabetic rats.     

Effect of grape (Vitis vinifera L.) leaf extract on alcohol induced oxidative stress in rats

Alcoholic liver disease is a major medical complication of drinking alcohol. Oxidative stress plays an important role in the development of alcohol liver disease. The present study was carried to evaluate the effect of grape leaf extract (GLEt) on antioxidant and lipid peroxidation states in liver and kidney alcohol induced toxicity. In vitro studies with DPPH* and ABTS*(+) (cation radical) showed that GLEt possesses antioxidant activity. In vivo administration of ethanol (7.9 g/kg bw/day) for 45 days resulted an activity of liver marker enzymes (AST, ALT, ALP and GGT), lipid peroxidation markers (TBARS, lipid hydroperoxides) in liver and kidney with significantly lower activity of SOD, CAT, GPx, GST and non-enzymatic antioxidants (vitamin E, vitamin C and GSH) in liver and kidney as compared with control rats. Administration of ethanol along with GLEt significantly decreased the activities of liver markers enzyme in serum towards near normal level. GLEt at a dose of 100 mg/kg was highly effective than 25 and 50 mg/kg body weight. In addition GLEt also significantly reduced the levels of lipid peroxidation and addition, significantly restored the enzymic and non-enzymatic antioxidants level in liver and kidney of alcohol administration rats. This observation was supplemented by histopathological examination in liver and kidney. Our data suggest that GLEt exerts its protective effect by decreased the lipid peroxidation and improving antioxidants status, thus proving itself as an effective antioxidant in alcohol induced oxidative damage in rats.     

Bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione (a curcumin analog) ameliorates DMH-induced hepatic oxidative stress during colon carcinogenesis.

The protective effect of a curcumin analog [bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione] was investigated on hepatic lipid peroxidation (LPO) and antioxidant status during 1,2-dimethylhydrazine-induced colon carcinogenesis in male Wistar rats. The effects were compared with that of curcumin, a known antioxidant and anticarcinogen. Colon cancer was induced by sub-cutaneous injection of DMH at a dosage of 20mg/kg body weight (15 doses, at 1-week intervals). DMH administered rats developed gross tumours in the colon. Enhanced lipid peroxidation in the liver of colon tumour bearing rats was accompanied by a significant decrease in the activities of glutathione peroxidase (GPx), glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT). Intragastric administration of curcumin (80mg/kg body weight) and curcumin analog (80mg/kg body weight) to DMH-injected rats significantly reduced the number and size of tumour in the colon, lowered lipid peroxidation and enhanced the activities of GPx, GST, SOD and CAT in the liver. We speculate that the curcumin analog used in the present study exerts chemoprevention against cancer development at extrahepatic sites by modulating hepatic biotransformation enzymes and antioxidant status. The effect is comparable with that of curcumin. This shows that the hydroxyl group in the aromatic ring is responsible for the protective effect rather than the methoxy group.     

Effect of chronic arsenic exposure under environmental conditions on bioaccumulation,oxidative stress,and antioxidant enzymatic defenses in wild trout <Emphasis Type="Italic">Salmo trutta</Emphasis> (Pisces,Teleostei)

The present study evaluates the relation between chronic arsenic (As) exposure in the natural distribution area of wild brown trout (Salmo trutta), oxidative stress and antioxidant enzymatic defenses. Two rivers of the same watershed were evaluated to highlight the correlation between As accumulation and the resulting stress: (i) the Presa River, which has high chronic As levels (2281.66?µg/L) due to past mining activity, and (ii) the Bravona River (control river). This metalloid was measured in main fish tissues (gills, kidney, liver, muscle, gonads and fins) and water. As organotropism in S. trutta was kidney?>?liver?>?gill?>?fin?>?gonad?>?muscle. The HepatoSomatic Index (HSI) and somatic condition (CF) were used to compare fish population conditions from both sites. Arsenic can be absorbed by the gills and can induce oxidative stress and disturb antioxidant defenses. The aim of this study was to evaluate oxidative stress response by measuring malondialdehyde (MDA) content, as a marker of lipid peroxidation, and antioxidant enzymatic defenses (Superoxide dismutase (SOD), catalase CAT, glutathione peroxidase (GPx) and glutathione S-transferase (GST)), in the main tissues of control and exposed trout. The highest MDA content was found in the kidney and liver of exposed trout. SOD and CAT activities in exposed livers and kidneys were considerably increased while a significant rise of GPx activity was observed only in the liver. GST activity was found to be significantly induced in the liver of exposed trout. The results demonstrate that arsenic bioaccumulation can induce lipid peroxidation and substantial modifications in antioxidant enzymatic defenses in main wild trout tissues.     

Chemoprotective effects of ethanolic extract of neem leaf against MNNG-induced oxidative stress

We evaluated the modifying effects of ethanolic extract of neem leaves (Azadirachta indica A. Juss) on oxidative stress induced by the potent gastric carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in male Wistar rats. The extent of lipid peroxidation and the status of the antioxidants superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were used as intermediate endpoints of chemoprevention. Three different concentrations of ethanolic neem leaf extract (100, 200 and 400 mg kg(-1) body weight) were administered by intragastric intubation (i.g) for five consecutive days followed by MNNG (i.g) 1.5 h after the final administration. Enhanced lipid peroxidation was accompanied by compromised antioxidant defences in the stomach, liver and erythrocytes of MNNG-treated rats. Pretreatment with ethanolic neem leaf extract at a dose of 200 mg/kg body weight (bw) significantly lowered the concentration of lipid peroxides and increased antioxidant levels. Our results demonstrate that neem leaf exerts its chemoprotective effects on MNNG- induced oxidative stress by decreasing lipid peroxidation and enhancing the antioxidant status.     

Time-dependent oxidative stress responses after acute exposure to toxic cyanobacterial cells containing microcystins in tilapia fish (Oreochromis niloticus) under laboratory conditions

Microcystins (MCs) have been reported to induce oxidative stress in aquatic organisms including fish. The effect of acute exposure to toxic cyanobacterial material containing MCs on antioxidant enzymes and lipid peroxidation has been studied in liver, kidney and gills of tilapia fish (Oreochromis niloticus). Fish were orally exposed to a single dose of cyanobacterial cells containing 120 microg/fish MC-LR and sacrificed at 24 and 72 h. The activities of glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) enzymes in the studied organs decreased in general 24 and 72 h after the dose application, although elevation of CAT and GR was found in liver at 72 h post exposure in comparison to 24h values. In contrast, the lipid peroxidation level increased significantly in all the studied organs with the liver (3.6-fold) proving to be the most affected. Protein oxidation was also increased 1.5-fold in the liver. However, recovery in these parameters was observed in liver 72 h after exposure. The results show that an acute dose of MCs does not induce an adaptative response of the antioxidant enzymes, as a sub-chronic exposure to MCs in tilapia fish does, but a general decrease in them with an initial recovery of the oxidative damage after 72 h, expressed as enhancement of CAT and GR activities and a reduction of LPO and protein oxidation in comparison to 24h values.     

Protective effects of lotus (Nelumbo nucifera Gaertn) germ oil against carbon tetrachloride-induced injury in mice and cultured PC-12 cells

The protective effects of lotus germ oil on liver and kidney damage by carbon tetrachloride-induced chronic hepatotoxicity in mice, PC-12 cells, and DNA damage were investigated. The mice were treated orally with lotus germ oil or dl-α-tocopherol after administration CCl₄ for 49 consecutive days. The levels of key antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and the concentration of glutathione (GSH), as well as the concentration of malondialdehyde (MDA), an indicator of lipid peroxidation, were determined in homogenates of the liver and the kidney. The pathological histology of the liver was also examined. The activities of SOD, CAT, and the concentration of GSH were increased significantly (p < 0.05–0.01) after treated with lotus germ oil in a concentration-dependent manner. Whereas, the content of the peroxidation product MDA were decreased significantly (p < 0.05), similar to the serum levels of hepatic enzyme biomarkers (alanine aminotransferase and aspartate aminotransferase). Furthermore, lotus germ oil could inhibit the conversion of super-coiled pBR322 plasmid DNA to the open circular form and apoptosis of hydrogen peroxide-induced PC-12 cells. The result of this study suggested that the lotus germ oil could be recognized as powerful “functional oil” against oxidative stress.     

Antioxidant and hepatoprotective activities of phenolic rich fraction of Seabuckthorn (Hippophae rhamnoides L.) leaves

Present study was aimed to investigate antioxidant and hepatoprotective activities of phenolic rich fraction (PRF) of Seabuckthorn leaves on CCl₄ induced oxidative stress in Sprague Dawley rats. Total phenolic content was found to be 319.33 mg gallic acid equivalent (GAE)/g PRF and some of its phenolic constituents, such as gallic acid, myricetin, quercetin, kaempferol and isorhamnetin were found to be in the range of 1.935-196.89 mg/g of PRF as determined by reverse-phase high-performance liquid chromatography (RP-HPLC).Oral administration of PRF at dose of 25-75 mg/kg body weight significantly protected from CCl₄ induced elevation in aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT) and bilirubin in serum, elevation in hepatic lipid peroxidation, hydroperoxides, protein carbonyls, depletion of hepatic reduced glutathione (GSH) and decrease in the activities of hepatic antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR) and glutathione-S-transferase (GST). The PRF also protected against histopathological changes produced by CCl₄ such as hepatocytic necrosis, fatty changes, vacuolation, etc. The data obtained in the present study suggests that PRF has potent antioxidant activity, prevent oxidative damage to major biomolecules and afford significant protection against CCl₄ induced oxidative damage in the liver.     

Amelioration of cyclophosphamide-induced hepatotoxicity by the root extract of Decalepis hamiltonii in mice

Hepatoprotective potential of the aqueous extract of the roots of Decalepis hamiltonii (DHA) against cyclophosphamide (CP)-induced oxidative stress has been investigated in mice. Administration of CP (25 mg/kg b.w., i.p) for 10 days induced hepatic damage as indicated by the serum marker enzymes aspartate and alanine transaminases (AST, ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). Parallel to these changes CP induced oxidative stress in the liver as evident from the increased lipid peroxidation (LPO), reactive oxygen species (ROS), depletion of glutathione (GSH), and reduced activities of the antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S-transferase (GST). Treatment with DHA (50 and 100 mg/kg b.w., po) mitigated the CP-induced oxidative stress. Moreover, expression of genes for the antioxidant enzymes, were down-regulated by CP treatment which was reversed by DHA. Our study shows the DHA protected the liver from toxicity induced by CP and therefore, it could be serve as a safe medicinal supplement during cyclophosphamide chemotherapy.     

Oxidative stress in ovariectomy menopause and role of chondroitin sulfate

Oxidative stress due to reactive oxygen species (ROS) can cause oxidative damage to cells. Cells have a number of defense mechanisms to protect themselves from the toxicity of ROS. Mitochondria are especially important in the oxidative stress as ROS have been found to be constantly generated as an endogen threat. Mitochondrial defense depends mainly on superoxide dismutase (SOD) and glutathione peroxidase (GPx), whereas microsomal defense depends on catalase (CAT), which is an enzyme abundant in microsomes. SOD removes superoxide anions by converting them to H2O2, which can be rapidly converted to water by CAT and GPx. Also, GPx converts hydroperoxide (ROOH) into oxidized-glutathione (GSSG). Ovariectomized (OVX) rats are used as an oxidative stress model. An ovariectomy increased the levels of MDA, one of the end-products in the lipid peroxidative process, and decreased levels of the antioxidative enzymes; SOD, CAT and GPx. However, Chondroitin sulfate (CS) decreased the levels of MDA, but increased the levels of SOD, CAT and GPx in a dose-dependent manner. Moreover, inflammation and cirrhosis of liver tissue in CS- treated rats were significantly decreased. These results suggest that CS might be a potential candidate as an antioxidative reagent.     

Protective effect of gallic acid against lindane induced toxicity in experimental rats

Lindane is an organochlorine pesticide that persists in the environment, bioaccumulate through food chain and has a risk of causing adverse effects to human health and the environment. It induces cell damage by producing free radicals and reactive oxygen species. The aim of the present study is to investigate the protective effect of gallic acid (a plant derived polyphenol) against lindane induced hepatic and renal toxicity in rats. Liver damage was assessed by hepatic serum marker enzymes like SGOT, SGPT and ALP and histopathological observation. Renal damage was observed by histopathological examination and serum markers like creatinine and urea. Treatment with lindane increased the levels of lipid peroxidation, serum marker enzyme activity with a concomitant decrease in GSH, CAT, SOD, GPx and GST. Histological alterations were also observed in kidney and liver tissue with lindane treatment. Co-treatment of gallic acid significantly prevented the lindane induced alterations in kidney and liver tissues with a decrease in LPO, serum marker enzyme activity and a significant increase in antioxidant levels. These results suggest that gallic acid has protective effect over lindane induced oxidative damage in rat liver and kidney.     

Rainbow trout (<Emphasis Type="Italic">Oncorhynchus mykiss</Emphasis>) pro-oxidant and genotoxic responses following acute and chronic exposure to the antibiotic oxytetracycline

Oxytetracycline (OTC), an antibacterial agent, is extensively used in aquaculture practices all over the world, but also in human and veterinary medicines. Because of its intensive use, low rates of absorption by treated animals, inadequate disposal, and low efficiency of removal in wastewater treatment plants, the potential harmful effects on aquatic organisms are of great concern. This work aimed to assess the effects of this antibiotic in rainbow trout, following both acute and chronic exposures. Catalase (CAT), total glutathione peroxidase (GPx), glutathione reductase (GRed) activities and lipid peroxidation (TBARS levels) were quantified as oxidative stress biomarkers, in gills and liver. Genotoxic endpoints, reflecting different types of genetic damage in blood cells, were also determined, by analysis of genetic damage (determination of the genetic damage index, GDI, measured by comet assay) and erythrocytic nuclear abnormalities (ENAs). The obtained results showed a mild pattern of antioxidant response, with modifications in CAT and GPx activities in gills, and lipid peroxidation in liver. These results suggest that despite the occurrence of oxidative effects, a full scenario of oxidative stress is not likely. However, exposure to OTC resulted in the establishment of genotoxic alterations with the induction of DNA strand breaks in blood cells (increase of GDI), and of chromosome breakage and/or segregational abnormalities (increase of ENAs). Considering that the oxidative response was not totally devisable, other mechanisms may be involved in the genotoxic effects reported.