Hepatoprotective effect of green tea (Camellia sinensis) extract against tamoxifen-induced liver injury in rats

Tamoxifen citrate (TAM), is widely used for treatment of breast cancer. It showed a degree of hepatic carcinogenesis. The purpose of this study was to elucidate the antioxidant capacity of green tea (Camellia sinensis) extract (GTE) against TAM-induced liver injury. A model of liver injury in female rats was done by intraperitoneal injection of TAM in a dose of 45mg Kg(-1) day(-1), i.p. for 7 successive days. GTE in the concentration of 1.5 %, was orally administered 4 days prior and 14 days after TAM-intoxication as a sole source of drinking water. The antioxidant flavonoid; epicatechin (a component of green tea) was not detectable in liver and blood of rats in either normal control or TAM-intoxicated group, however, TAM intoxication resulted in a significant decrease of its level in liver homogenate of tamoxifenintoxicated rats. The model of TAM-intoxication elicited significant declines in the antioxidant enzymes (glutathione-S-transferase,glutathione peroxidase, superoxide dismutase and catalase) and reduced glutathione concomitant with significant elevations in TBARS (thiobarbituric acid reactive substance) and liver transaminases; sGPT (serum glutamate pyruvate transaminase) and sGOT (serum glutamate oxaloacetate transaminase) levels. The oral administration of 1.5 % GTE to TAM-intoxicated rats, produced significant increments in the antioxidant enzymes and reduced glutathione concomitant with significant decrements in TBARS and liver transaminases levels. The data obtained from this study speculated that 1.5 % GTE has the capacity to scavenge free radical and can protect against oxidative stress induced by TAM intoxication. Supplementation of GTE could be useful in alleviating tamoxifen-induced liver injury in rats.     

Hepatoprotective and antioxidant effect of tender coconut water on carbon tetrachloride induced liver injury in rats

Hepatoprotective and antioxidant effects of tender coconut water (TCW) were investigated in carbon tetrachloride (CCl4)-intoxicated female rats. Liver damage was evidenced by the increased levels of serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and decreased levels of serum proteins and by histopathological studies in CCl4-intoxicated rats. Increased lipid peroxidation was evidenced by elevated levels of thiobarbituric acid reactive substance (TBARS) viz, malondialdehyde (MDA), hydroperoxides (HP) and conjugated dienes (CD), and also by significant decrease in antioxidant enzymes activities, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx) and glutathione reductase (GR) and also reduced glutathione (GSH) content in liver. On the other hand, CCl4-intoxicated rats treated with TCW retained almost normal levels of these constituents. Decreased activities of antioxidant enzymes in CCl4-intoxicated rats and their reversal of antioxidant enzyme activities in TCW treated rats, shows the effectiveness of TCW in combating CCl4-induced oxidative stress. Hepatoprotective effect of TCW is also evidenced from the histopathological studies of liver, which did not show any fatty infiltration or necrosis, as observed in CCl4-intoxicated rats.     

Dietary glycine inhibits activation of nuclear factor kappa B and prevents liver injury in hemorrhagic shock in the rat.

We investigated the effects of a glycine-containing diet (5%) on liver injury caused by hemorrhagic shock and resuscitation in rats. Anesthetized rats were bled to a mean arterial blood pressure of 35-40 mm Hg for 1 h and then resuscitated with 60% of shed blood and lactated Ringer's solution. Feeding the rats glycine significantly reduced mortality, the elevation of plasma transaminase levels and hepatic necrosis. The increase in plasma TNFalpha and nitric oxide (NO) was also blunted by glycine feeding. Hemorrhagic shock resulted in oxidative stress (significant elevations in TBARS and in the oxidized/reduced glutathione ratio) and was accompanied by a reduced activity of the antioxidant enzymes Mn- and Cu,Zn-superoxide dismutase, glutathione peroxidase and catalase, overexpression of inducible NO synthase (iNOS), and activation of nuclear factor kappa B (NF-kappaB). Glycine ameliorated oxidative stress and the impairment in antioxidant enzyme activities, inhibited NF-kappaB activation, and prevented expression of iNOS. Dietary glycine blocks activation of different mediators involved in the pathophysiology of liver injury after shock.     

Chronic unpredictable stress exacerbates 7,12-dimethylbenz (a) anthracene induced hepatotoxicity and nephrotoxicity in Swiss albino mice

Oxidative stress, a pervasive condition induced by stress has been implicated and recognized to be a prominent feature of various pathological states including cancer and their progression. The present study sought to validate the effectiveness of chronic unpredictable stress (CUS) on hepatic and renal toxicity in terms of alterations of various in vivo biochemical parameters, oxidative stress markers and the extent of DNA damage in Swiss albino mice. Animals were randomized into different groups based on their exposure to CUS alone, 7,12-dimethylbenz (a) anthracene (DMBA) alone (topical), DMBA-12-O-tetradecanoylphorbol-13-acetate (TPA) (topical), and exposure to CUS prior to DMBA or DMBA-TPA treatment, and sacrificed after 16 weeks of treatment. Prior exposure to CUS increased the pro-oxidant effect of carcinogen as depicted by significantly compromised levels of antioxidants; superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase, reduced glutathione in hepatic and renal tissues accompanied by a significant elevation of thiobarbituric acid reactive species (TBARS) as compared to DMBA alone or DMBA-TPA treatments. Loss of structural integrity at the cellular level due to stress-induced oxidative damage was demonstrated by significant increases in the hepatic levels of intracellular marker enzymes such as glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and alkaline phosphatase, and significantly reduced levels of uric acid in kidney tissues. The results of DNA damage studies further positively correlated with all the above biochemical measurements. Thus, exposure to physical or psychological stress may significantly enhance the hepatotoxic and nephrotoxic potential of carcinogens through enhanced oxidative stress even if the treatment is topical.     

Protective effects of dietary cyanidin 3-O-beta-D-glucoside on liver ischemia-reperfusion injury in rats.

We recently reported that feeding cyanidin 3-O-beta-d-glucoside (C3G), a typical anthocyanin pigment, lowered the serum thiobarbituric acid-reactive substance (TBARS) concentration and increased the oxidation resistance of the serum to lipid peroxidation in rats. These results suggest that C3G acts as a potent antioxidant in vivo when acute oxidative stress is encountered. In the present study, we evaluated whether feeding C3G suppresses oxidative injury to the liver caused by hepatic ischemia-reperfusion (I/R), which was used as a model for oxidative stress. Rats were fed a diet containing C3G (2 g/kg diet) for 14 days and then subjected to hepatic I/R. I/R treatment elevated the liver TBARS concentration and the serum activities of marker enzymes (glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactate dehydrogenase) for liver injury and lowered the liver reduced glutathione concentration. Feeding C3G significantly suppressed these changes caused by hepatic I/R. Although the liver ascorbic acid concentration was also lowered by hepatic I/R, feeding C3G restored this concentration more quickly compared to the control rats. These results indicate that orally administered C3G suppresses I/R-induced oxidative damage and suggest that C3G functions as a potent antioxidant in vivo under oxidative stress.     

24-hour rhythms in oxidative stress during hepatocarcinogenesis in rats: effect of melatonin or alpha-ketoglutarate

To compare the effects of alpha-ketoglutarate (alpha-KG) and melatonin on 24-h rhythmicity of oxidative stress in N-nitrosodiethylamine (NDEA)-injected Wistar male rats, melatonin (5 mg/kg i.p.) or alpha-KG (2 g/kg through an intragastric tube) was given daily for 20 weeks. In blood collected at 6 time points during a 24-h period, serum activity of aspartate transaminase (AST) and alanine transaminase (ALT) and the levels of alpha-fetoprotein (alpha-FP) were measured as markers of liver function. To assess lipid peroxidation and the antioxidant status, plasma levels of thiobarbituric acid reactive substances (TBARS) and of reduced glutathione (GSH) were measured, together with the activity of erythrocyte superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST). NDEA augmented mesor and amplitude of rhythms in AST and ALT activity and plasma alpha-FP levels and mesor values of plasma TBARS, while decreasing mesor values of plasma GSH and erythrocyte SOD, CAT, GPx and GST. Acrophases were delayed by NDEA in all cases except for alpha-FP rhythm, which became phase-advanced. Co-administration of melatonin or alpha-KG partially counteracted the effects of NDEA. Melatonin decreased mesor of plasma TBARS and augmented mesor of SOD activity. The results indicate that melatonin and alpha-KG are effective in protecting from NDEA-induced perturbation of 24-h rhythms in oxidative stress. Melatonin augmented antioxidant defense in rats.     

Resveratrol attenuates hyperglycemia-mediated oxidative stress,proinflammatory cytokines and protects hepatocytes ultrastructure in streptozotocin–nicotinamide-induced experimental diabetic rats

The present study was hypothesized to investigate the hepatoprotective nature of resveratrol in averting hyperglycemia-mediated oxidative stress by measuring extent of oxidant stress and levels of proinflammatory cytokines and antioxidant competence in the hepatic tissues of streptozotocin–nicotinamide-induced diabetic rats. After the experimental period of 30 days, the pathophysiological markers such as serum bilirubin and hepatic aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were studied in addition to hepatic TNF-α, IL-1β, IL-6, NF-κB p65 and nitric oxide (NO) levels in control and experimental groups of rats. The levels of vitamin C, vitamin E and reduced glutathione (GSH) and activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) were determined in the liver tissues. Extent of oxidative stress was also assessed by hepatic lipid peroxides, hydroperoxides and protein carbonyls. A portion of liver was processed for histological and ultrastructural studies. Oral administration of resveratrol (5 mg/kg b.w.) to diabetic rats showed a significant decline in hepatic proinflammatory cytokines and notable attenuation in hepatic lipid peroxides, hydroperoxides and protein carbonyls. The diminished activities of hepatic enzymic antioxidants as well as the decreased levels of hepatic non-enzymic antioxidants of diabetic rats were reverted to near normalcy by resveratrol administration. Moreover, the histological and ultrastructural observations evidenced that resveratrol effectively rescues the hepatocytes from hyperglycemia-mediated oxidative damage without affecting its cellular function and structural integrity. The findings of the present investigation demonstrated the hepatocyte protective nature of resveratrol by attenuating markers of hyperglycemia-mediated oxidative stress and antioxidant competence in hepatic tissues of diabetic rats.     

Ameliorative potential of S-allyl cysteine on oxidative stress in STZ induced diabetic rats

Increased oxidative stress and impaired antioxidant defense mechanism are important factors in the pathogenesis and progression of diabetes mellitus and other oxidant-related diseases. The present study was undertaken to evaluate the possible protective effects of S-allyl cysteine (SAC) against oxidative stress in streptozotocin (STZ) induced diabetic rats. SAC was administered orally for 45 days to control and STZ induced diabetic rats. The effects of SAC on glucose, plasma insulin, thiobarbituric acid reactive substances (TBARS), hydroperoxide, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), oxidized glutathione (GSSG) and GSH/GSSG ratio were studied. The levels of glucose, TBARS, hydroperoxide, and GSSG were increased significantly whereas the levels of plasma insulin, reduced glutathione, GSH/GSSG ratio, superoxide dismutase, catalase and GPx were decreased in STZ induced diabetic rats. Administration of SAC to diabetic rats showed a decrease in plasma glucose, TBARS, hydroperoxide and GSSG. In addition, the levels of plasma insulin, superoxide dismutase, catalase, GPx and reduced glutathione (GSH) were increased in SAC treated diabetic rats. The above findings were supported by histological observations of the liver and kidney. The antioxidant effect of SAC was compared with glyclazide, a well-known antioxidant and antihyperglycemic drug. The present study indicates that the SAC possesses a significant favorable effect on antioxidant defense system in addition to its antidiabetic effect.     

Protective effect of Indian honey on acetaminophen induced oxidative stress and liver toxicity in rat

The present study was undertaken to investigate the protective effect of Indian honey on acetaminophen induced oxidative stress and liver damage in rat. Honey serves as a source of natural medicine, which is effective to reducing the risk of heart disease, liver toxicity and inflammatory processes. The hepatoprotective activity of the Indian honey was determined by assessing levels of Serum transaminases, ALP and total bilirubin. Finally, the effects of the test substances on the antioxidant enzymes of the liver were also studied by assessing changes in the level of reduced glutathione, glutathione peroxidase, catalase and superoxide dismutase. Serum transaminase, ALP and total bilirubin level were significantly elevated and the antioxidant status in liver such as activities of SOD, CAT, GPx and the levels of GSH were declined significantly in APAP alone treated animals. Pretreatment with honey and silymarin prior to the administration of APAP significantly prevented the increase in the serum levels of hepatic enzyme markers and reduced oxidative stress. The histopathological evaluation of the livers also revealed that honey reduced the incidence of liver lesions induced by APAP. Results suggest that the Indian honey protects liver against oxidative damage and it could be used as an effective hepatoprotector against APAP induced liver damage.     

Endogenous antioxidant defence system in rat liver following mercury chloride oral intoxication

Mercury is a highly toxic metal which induces oxidative stress. Superoxide dismutases, catalase, and glutathion peroxidase are proteins involved in the endogenous antioxidant defence system. In the present study rats were administered orally, by gavage, a single daily dose of HgCl2 for three consecutive days. In order to find a relation between the proteins involved in the antioxidant defence and mercury intoxication, parameters of liver injury, redox state of the cells, as well as intracellular protein levels and enzyme activities of Mn-dependent superoxide dismutase (MnSOD), Cu-Zn-dependent superoxide dismutase (CuZnSOD), catalase, and glutathione peroxidase (GPx) were assayed both in blood and in liver homogenates. HgCl2 at the doses of 0.1 mg/kg produced liver damage which that was detected by a slight increase in serum alanine aminotransferase and gamma glutamyl transferase. Hepatic GSH/GSSG ratio was assayed as a parameter of oxidative stress and a significant decrease was detected, as well as significant increases in enzyme activities and protein levels of hepatic antioxidant defence systems. Changes in both MnSOD and CuZnSOD were parallel to those of liver injury and oxidative stress, while the changes detected in catalase and GPx activities were progressively increased along with the mercury intoxication. Other enzyme activities related to the glutathione redox cycle, such as glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH), also increased progressively. We conclude that against low doses of mercury that produce a slight oxidative stress and liver injury, the response of the liver was to induce the synthesis and activity of the enzymes involved in the endogenous antioxidant system. The activities of all the enzymes assayed showed a rapidly induced coordinated response.     

Anti-oxidative effect of a protein from Cajanus indicus L against acetaminophen-induced hepato-nephro toxicity

Overdoses of acetaminophen cause hepato-renal oxidative stress. The present study was undertaken to investigate the protective effect of a 43 kDa protein isolated from the herb Cajanus indicus, against acetaminophen-induced hepatic and renal toxicity. Male albino mice were treated with the protein for 4 days (intraperitoneally, 2 mg/kg body wt) prior or post to oral administration of acetaminophen (300 mg/kg body wt) for 2 days. Levels of different marker enzymes (namely, glutamate pyruvate transaminase and alkaline phosphatase), creatinine and blood urea nitrogen were measured in the experimental sera. Intracellular reactive oxygen species production and total antioxidant activity were also determined from acetaminophen and protein treated hepatocytes. Indices of different antioxidant enzymes (namely, superoxide dismutase, catalase, glutathione-S-transferase) as well as lipid peroxidation end-products and glutathione were determined in both liver and kidney homogenates. In addition, Cytochrome P450 activity was also measured from liver microsomes. Finally, histopathological studies were performed from liver sections of control, acetaminophen-treated and protein pre- and post-treated (along with acetaminophen) mice. Administration of acetaminophen increased all the serum markers and creatinine levels in mice sera along with the enhancement of hepatic and renal lipid peroxidation. Besides, application of acetaminophen to hepatocytes increased reactive oxygen species production and reduced the total antioxidant activity of the treated hepatocytes. It also reduced the levels of antioxidant enzymes and cellular reserves of glutathione in liver and kidney. In addition, acetaminophen enhanced the cytochrome P450 activity of liver microsomes. Treatment with the protein significantly reversed these changes to almost normal. Apart from these, histopathological changes also revealed the protective nature of the protein against acetaminophen induced necrotic damage of the liver tissues. Results suggest that the protein protects hepatic and renal tissues against oxidative damages and could be used as an effective protector against acetaminophen induced hepato-nephrotoxicity.     

mRNA expression of antioxidant enzymes (SOD, CAT and GSH-Px) and lipid peroxidative stress in liver of Atlantic salmon (Salmo salar) exposed to hyperoxic water during smoltification

The mRNA levels of three antioxidant genes, Cu/Zn superoxide dismutase (SOD), catalase (CAT) and phospholipid hydroperoxide glutathione peroxidase (GSH-Px), were quantified with real-time qRT-PCR in liver of Atlantic salmon Salmo salar exposed to 80% (normoxia), 105% and 130% O2 saturation for 54 days. The salmon were then translocated and exposed to 90% and 130% O2 saturation for additional 72 days during smoltification. TBARS and vitamin E levels in liver and the levels of oxidized glutathione (GSSG), total glutathione (GSH) and the resulting oxidative stress index (OSI) in blood were quantified as traditional oxidative stress markers. No significant mean normalized expression (MNE) differences of SOD, CAT or GSH-Px were found in liver after hyperoxia exposure at the two sampling times. Significantly decreased OSI was found in smolt exposed to 130% O2 saturation after 126 days (n = 18, P < 0.0001), indicating hyperoxia-induced oxidative stress. No effects were seen on growth, or on the levels of thiobarbituric reactive substances (TBARS) and vitamin E in liver after the exposure experiment. Overall, the mRNA expression of SOD, CAT and GSH-Px in liver related poorly with the hyperoxic exposure regimes, and more knowledge are needed before the expressed levels of these antioxidant genes can be applied as biomarkers of hyperoxia in Atlantic salmon.     

Hyperoxia results in transient oxidative stress and an adaptive response by antioxidant enzymes in goldfish tissues

The effects of hyperoxia on the status of antioxidant defenses and markers of oxidative damage were evaluated in goldfish tissues. The levels of lipid peroxides, thiobarbituric acid reactive substances, carbonyl proteins and the activities of some antioxidant enzymes were measured in brain, liver, kidney and skeletal muscle of goldfish, Carassius auratus L., over a time course of 3-12 h of hyperoxia exposure followed by 12 or 36 h of normoxic recovery. Exposure to high oxygen resulted in an accumulation of protein carbonyls in tissues throughout hyperoxia and recovery whereas lipid peroxides and thiobarbituric acid reactive substances accumulated transiently under short-term hyperoxia stress (3-6 h) but were then strongly reduced. This suggests that hyperoxia stimulated an enhancement of defenses against lipid peroxidation or mechanisms for enhancing the catabolism of peroxidation products. The activities of principal antioxidant enzymes, superoxide dismutase and catalase, were not altered under hyperoxia but catalase increased during normoxic recovery; activities may rise in anticipation of further hyperoxic excursions. In most tissues, the activities of glutathione-utilizing enzymes (glutathione peroxidase, glutathione-S-transferase, glutathione reductase) as well as glucose-6-phosphate dehydrogenase, were not affected under hyperoxia but increased sharply during normoxic recovery. Correlations between some enzyme activities and oxidative stress markers were found, for example, an inverse correlation was seen between levels of thiobarbituric acid reactive substances and glutathione-S-transferase activity in liver and catalase and glucose-6-phosphate dehydrogenase in kidney. The results suggest that liver glutathione-S-transferase plays an important role in detoxifying end products of lipid peroxidation accumulated under hyperoxia stress.     

Combined efficacies of lipoic acid and 2,3-dimercaptosuccinic acid against lead-induced lipid peroxidation in rat liver

Oxidative stress with subsequent lipid peroxidation has been postulated as one mechanism for lead toxicity. Hence in assessing the protective effects of lipoic acid (LA) and meso 2,3-dimercaptosuccinic acid (DMSA) on lead toxicity, they were tested either separately or in combination for their effects on selected indices of hepatic oxidative stress. Elevated levels of lipid peroxides were accompanied by altered antioxidant defense systems. Lead acetate (Pb - 0.2%) was administered in drinking water for five weeks to induce toxicity. LA (25 mg kg(-1) body wt. day(-1) i.p) and DMSA (20 mg kg(-1) body wt. day(-1) i.p) were administered individually and also in combination during the sixth week. Lead damage to the liver was evident in the decreases in hepatic enzymes alanine transaminase (-38%), aspartate transaminase (-42%) and alkaline phosphatase (-43%); increases in lipid peroxidation (+38%); decreases in the antioxidant enzymes catalase (-45%), superoxide dismutase (-40%), glutathione peroxidase (-46%) and decreases in glutathione (-43%) and decreases in glutathione metabolizing enzymes, glutathione reductase (-59%), glucose-6-phosphate dehydrogenase (-27%) and glutathione-S-transferase (-42%). In combination LA and DMSA completely ameliorated the lead induced oxidative damage. Either compound alone was however only partially protective against lead damage.     

Responses of glutathione system and antioxidant enzymes to exhaustive exercise and hydroperoxide.

Glutathione (gamma-glutamylcysteinylglycine) is one of the major antioxidants in the body. The present study investigated the changes of glutathione status, oxidative injury, and antioxidant enzyme systems after an exhaustive bout of treadmill running and/or hydroperoxide injection in male Sprague-Dawley rats. Concentrations of total and reduced glutathione in deep vastus lateralis muscle were significantly increased (P less than 0.01) after exhaustive exercise with either hydroperoxide (t-butyl hydroperoxide) or saline injection, whereas hydroperoxide alone had no significant effect. Exhaustive exercise increased muscle glutathione disulfide content by 75 and 60% (P less than 0.05), respectively, in hydroperoxide and saline groups. Concentrations of glutathione-related amino acids glutamate, cysteine, and aspartate were significantly increased in the same muscle after exhaustion. Hepatic glutathione status was not affected by either hydroperoxide injection or exercise. Glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase activities were significantly elevated after exhaustive exercise with or without hydroperoxide injection in muscle but not in liver. Hydroperoxide and exhaustive exercise enhanced lipid peroxidation in muscle and liver, respectively. It is concluded that exhaustive exercise can impose a severe oxidative stress on skeletal muscle and that glutathione systems as well as antioxidant enzymes are important in coping with free radical-mediated muscle injury.     

Amelioration of tamoxifen-induced liver injury in rats by grape seed extract, black seed extract and curcumin

Liver injury was induced in female rats using tamoxifen (TAM). Grape seeds (Vitis vinifera) extract (GSE), black seed (Nigella sativa) extract (NSE), curcumin (CUR) or silymarin (SYL) were orally administered to TAM-intoxicated rats. Liver histopathology of TAM-intoxicated:rats showed pathological changes. TAM-intoxication elicited declines in liver antioxidant enzymes levels (glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase), reduced glutathione (GSH) and GSH/GSSG ratio plus the hepatic elevations in lipid peroxides, oxidized glutathione (GSSG), tumor necrosis factor-alpha (TNF-alpha) and serum liver enzymes; alanine transaminase, aspartate transaminase, alkaline phosphatase, lactate dehydrogenase and gamma glutamyl transferase levels. Oral intake of NSE, GSE, CUR or SYL to TAM-intoxicated rats, attenuated histopathological changes and corrected all parameters mentioned above. Improvements were prominent in case of NSE (similarly SYL) > CUR > GSE. Data indicated that NSE, GSE or CUR act as free radicals scavengers and protect TAM-induced liver injury in rats.     

Penicillin-induced oxidative stress: effects on antioxidative response of midgut tissues in instars of Galleria mellonella

Penicillin and other antibiotics are routinely incorporated in insect culture media. Although culturing insects in the presence of antibiotics is a decades-old practice, antibiotics can exert deleterious influences on insects. In this article, we test the hypothesis that one of the effects of dietary penicillin is to increase oxidative stress on insects. The effects of penicillin on midgut concentrations of the oxidative stress indicator malondialdehyde (MDA) and on midgut antioxidant enzyme (superoxide dismutase [SOD], catalase [CAT], glutathione S-transferase [GST], and glutathione peroxidase [GPx]) and transaminases (alanine aminotransferase and aspartate aminotransferase) activities in greater wax moth, Galleria mellonella (L.), were investigated. The insects were reared from first instars on artificial diets containing 0.001, 0.01, 0.1, or 1.0 g penicillin per 100 g of diets. MDA content was significantly increased in the midgut tissues of each larval instar reared in the presence of high penicillin concentrations. Activities of antioxidant and transaminase enzymes did not show a consistent pattern with respect to penicillin concentrations in diet or age of larvae. Despite the increased penicillin-induced oxidative stress in gut tissue, antioxidant and transaminase enzymes did not correlate with oxidative stress level or between each other in larvae of other age stages except for the seventh instar. We found a significant negative correlation of MDA content with SOD and GST activities in seventh instars. SOD activity was also negatively correlated with CAT activity in seventh instars. These results suggest that exposure to dietary penicillin resulted in impaired enzymatic antioxidant defense capacity and metabolic functions in wax moth larval midgut tissues and that the resulting oxidative stress impacts midgut digestive physiology.     

Effects of aging on the susceptibility to the toxic effects of cyclosporin A in rats. Changes in liver glutathione and antioxidant enzymes

Free radicals are involved in aging and cyclosporin A-induced toxicity. The age-related changes in the liver oxidative status of glutathione, lipid peroxidation, and the activity of the enzymatic antioxidant defense system, as well as the influence of aging on the susceptibility to the hepatotoxic effects of cyclosporin (CyA) were investigated in rats of different ages (1, 2, 4, and 24 months). The hepatic content of reduced glutathione (GSH) increased with aging, peaked at 4 months, and decreased in senescent rats. By contrast, glutathione disulfide (GSSG) and thiobarbituric acid-reactive substances (TBARS) concentrations and superoxide dismutase, catalase, and glutathione peroxidase activities were higher in the oldest than in the youngest rats. CyA treatment, besides inducing the well-known cholestatic syndrome, increased liver GSSG and TBARS contents and the GSSG/GSH molar ratio, and altered the nonenzymatic and enzymatic antioxidant defense systems. The CyA-induced cholestasis and hepatic depletion of GSH, and the increases in the GSSG/GSH ratio, and in GSSG and TBARS concentrations were higher in the older than the mature rats. Moreover, superoxide dismutase and catalase activities were found to be significantly decreased only in treated senescent rats. The higher CyA-induced oxidative stress, lipoperoxidation, and decreases in the antioxidant defense systems in the aged animals render them more susceptible to the hepatotoxic effects of cyclosporin.     

Effect of dietary sesame oil as antioxidant on brain hippocampus of rat in focal cerebral ischemia

Oxidative stress may be regarded as an imbalance between free radical production and opposing antioxidant defenses. Free radical oxidative stress is implicated in rat cerebral ischemia and naturaceutical antioxidants are dietary supplements that have been reported to have neuroprotective activity. Many studies have reported dietary sesame oil (SO) as an effective antioxidant. In the present study the neuroprotective effect of dietary SO was evaluated against middle cerebral artery occlusion (MCAO)-induced cerebral ischemia injury in rats. Rats were fed on diet (20% SO) for 15 days. The middle cerebral artery of adult male Wistar rat was occluded for 2 h and reperfused for 22 h. The antioxidant properties of brain were measured as levels of reduced glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxide (GPx), glutathione reductase (GR), catalase (CAT), superoxide dismutase (SOD) and thiobarbituric acid reactive substance (TBARS). A decrease in the activity of all the enzymatic and non-enzymatic antioxidants was observed along with an increase in lipid peroxidation (LPO) in MCAO group. The neurobehavioral activity of rats was also observed by using videopath analyzer. Dietary SO improved the antioxidant status in MCAO+SO group when compared with MCAO group. The results of neurobehavioral activity also support our biochemical data. The results obtained suggest protective effect of SO against cerebral ischemia in rat brain through their antioxidant properties.     

Temporal variations of lipid peroxidation products, antioxidants and liver marker enzymes in experimental hyperammonemic rats

Circadian variations of lipid peroxidation products: thiobarbituric acid and reactive substances (TBARS), antioxidants: reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and liver marker enzymes such as transaminases (aspartate transaminase (AST) and alanine transaminase (ALT), alkaline phosphatase (ALP) and γ-Glutamyl transpeptidase (GGT) in circulation were analysed in control and ammonium chloride (AC) induced (100 mg/kg bodyweight) hyperammonemic rats. Elevated lipid peroxidation and liver marker enzymes (increased mesor of TBARS, AST, ALT, ALP and GGT) associated with decreased activities of antioxidants (decreased mesor of GPx, GSH, SOD and CAT) were found in hyperammonemic rats. Variations in acrophase, amplitude and r values were also found in between the control and hyperammonemic rats. These alterations clearly indicate that temporal liver marker enzymes and redox status are modulated during hyperammonemic conditions, which may also play a crucial role in disease development.