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.     

The impact of cyanoglycoside rich fraction isolated from Cassava (Manihot esculenta) on alcohol induced oxidative stress.

The effects of feeding a cassava (Manihot esculenta) rich diet on alcohol induced peroxidative damages were investigated in male albino rats. Rats were divided into four groups and maintained for 60 days as follows. (1) Control group: cassava free diet, (2) alcohol group: cassava free diet+ethanol (4 g/kg body wt/day), (3) cassava group: cassava diet and (4) alcohol+cassava group: cassava diet+ethanol (4 g/kg body wt/day). Results revealed that alcohol induced significant lipid peroxidation, since the lipid peroxidation products malondialdehyde (MDA), hydroperoxides and conjugated dienes were elevated in the liver. The activities of free radical scavenging enzymes such as superoxide dismutase (SOD), catalase and glutathione reductase were reduced and glutathione content was decreased in the liver. But the co-administration of a cassava rich diet increased the activity of free radical scavenging enzymes and glutathione content. The level of lipid peroxides in the liver was also decreased on co-administration of cassava. But the oxidative damage caused by cassava was potentiated by alcohol administration. These studies suggested that consumption of alcohol along with cassava offered some protection against the alcohol induced oxidative stress. So we isolated the cyanoglycoside rich fraction from cassava and its impact on rats administered alcohol was also investigated. The results revealed that alcohol induced oxidative stress was potentiated by the co-administration of cyanoglycoside rich fraction. These studies suggested that the fiber and antioxidant vitamins present in the cassava may be playing a protective role against the alcohol induced oxidative stress.     

Biochemical evidence for free radical-induced lipid peroxidation as a mechanism for subchronic toxicity of malathion in blood and liver of rats

Organophosphorus compounds may induce oxidative stress leading to generation of free radicals and alterations in antioxidant and scavengers of oxygen free radicals (OFRs). The effect of subchronic exposure to malathion in the production of oxidative stress was evaluated in male Wistar rats. Administration of malathion (100, 316, 1000, 1500 ppm) for 4 weeks increased catalase (CAT), superoxide dismutase (SOD) activities as well as malondialdehyde (MDA) concentration in red blood cells (RBC) and liver. However, acetylcholinesterase (AChE) and cholinesterase (ChE) activities were decreased in these samples. The increase in RBC and liver lipid peroxidation correlated well with the inhibition in RBC AChE and liver ChE activities. Elevation of MDA concentrations and increased activities of CAT and SOD showed significant correlations in both RBC and liver samples when different doses of malathion were used. The results of the present study suggest the usefulness of RBC AChE measurement as a good biomarker in the estimation of malathion-induced oxidative stress affecting blood and liver.     

Protective effect of boldine on oxidative mitochondrial damage in streptozotocin-induced diabetic rats.

Increased oxidative stress has been suggested to be involved in the pathogenesis and progression of diabetic tissue damage. Several antioxidants have been described as beneficial for oxidative stress-associated diseases. Boldine ([s]-2,9-dihydroxy-1, 10-dimethoxyaporphine) is a major alkaloid found in the leaves and bark of boldo (Peumus boldus Molina), and has been shown to possess antioxidant activity and anti-inflammatory effects. From this point of view, the possible anti-diabetic effect of boldine and its mechanism were evaluated. The experiments were performed on male rats divided into four groups: control, boldine (100 mg kg(-1), daily in drinking water), diabetic [single dose of 80 mg kg(-1)of streptozotocin (STZ), i.p.] and diabetic simultaneously fed with boldine for 8 weeks. Diabetic status was evaluated periodically with changes of plasma glucose levels and body weight in rats. The effect of boldine on the STZ-induced diabetic rats was examined with the formation of malondialdehydes and carbonyls and the activities of endogenous antioxidant enzymes (superoxide dismutase and glutathione peroxidase) in mitochondria of the pancreas, kidney and liver. The scavenging action of boldine on oxygen free radicals and the effect on mitochondrial free-radical production were also investigated. The treatment of boldine attenuated the development of hyperglycemia and weight loss induced by STZ injection in rats. The levels of malondialdehyde (MDA) and carbonyls in liver, kidney and pancreas mitochondria were significantly increased in STZ-treated rats and decreased after boldine administration. The activities of mitochondrial manganese superoxide dismutase (MnSOD) in the liver, pancreas and kidney were significantly elevated in STZ-treated rats. Boldine administration decreased STZ-induced elevation of MnSOD activity in kidney and pancreas mitochondria, but not in liver mitochondria. In the STZ-treated group, glutathione peroxidase activities decreased in liver mitochondria, and were elevated in pancreas and kidney mitochondria. The boldine treatment restored the altered enzyme activities in the liver and pancreas, but not the kidney. Boldine attenuated both STZ- and iron plus ascorbate-induced MDA and carbonyl formation and thiol oxidation in the pancreas homogenates. Boldine decomposed superoxide anions, hydrogen peroxides and hydroxyl radicals in a dose-dependent manner. The alkaloid significantly attenuated the production of superoxide anions, hydrogen peroxide and nitric oxide caused by liver mitochondria. The results indicate that boldine may exert an inhibitory effect on STZ-induced oxidative tissue damage and altered antioxidant enzyme activity by the decomposition of reactive oxygen species and inhibition of nitric oxide production and by the reduction of the peroxidation-induced product formation. Boldine may attenuate the development of STZ-induced diabetes in rats and interfere with the role of oxidative stress, one of the pathogeneses of diabetes mellitus.     

Protective effect of Aplysin on hepatic injury in ethanol-treated rats

This study evaluated the protective effects of Aplysin against ethanol-induced hepatic injury in rats and analyzed the associated mechanisms. Rats were administered orally with ethanol 8–12 ml/kg bw excluding the rats in the control group at 1 h after rats were administered by gavage doses of Aplysin (50, 100, and 150 mg/kg bw) every day. After 6 weeks, rats were sacrificed, and liver injury was evaluated by biochemical and pathological examination. Hepatocyte apoptosis was analyzed by annexin V-FITC/PI staining. Ethanol metabolic enzymes, oxidative stress, mitochondrial function, and Bcl-2, Bax, cytochrome c and cleaved caspase-3 expressions were evaluated by western blot analysis. These results demonstrated that Aplysin exhibited a significant hepatoprotective effect. In the ethanol-treated group, cytochrome P4502E1 and alcohol dehydrogenase were increased significantly in liver tissue. Moreover, Aplysin not only significantly reversed the ratio of NAD⁺/NADH and mitochondrial glutathione depletion, but also reversed the decreased activity of mitochondrial respiratory chain complexes I, III and IV. Overexpression of cytoplasmic cytochrome c and caspase-3 activation was suppressed by Aplysin. These results suggest that Aplysin alleviates hepatocyte apoptosis by modulating the ethanol-metabolizing pathway, attenuating oxidative stress, ameliorating mitochondrial function, inhibiting mitochondrial damage-mediated apoptosis, which ultimately prevent and repair alcoholic liver injury.     

Effect of Aloe vera leaf gel and pulp extracts on the liver in type-II diabetic rat models

The aim of this work was to investigate the effects of Aloe vera leaf pulp and gel extracts on the liver tissue of neonatal streptozotocin (n0STZ)-induced type-II diabetic rats. The diabetic rats were separated into four groups and each group was given the following samples by gavage, daily for 15 d: phosphate buffered saline (PBS; diabetic control), Aloe leaf pulp extract, Aloe leaf gel extract, glibenclamide. Liver tissues were examined histologically. The markers of oxidative stress: glutathione (GSH), non-enzymatic glycosylation (NEG) and lipid peroxidation (LPO), were determined in liver tissue. Biochemical parameters for liver function: serum alkaline phosphatase (ALP), and alanine transaminase (ALP) activities, were evaluated. All parameters were also determined in healthy (non diabetic) rats for comparison. In the diabetic control group, the degenerative changes in liver tissue were remarkable, while in the diabetic groups given Aloe pulp and gel extracts and glibenclamide, the damage to the liver tissue was decreased. The increase of GSH and the decrease of NEG and LPO in liver tissues with the treatment of Aloe gel extract, is consistent with the beneficial effect of Aloe. Serum ALP and ALT activities were also decreased in the groups given Aloe gel extract. It was concluded that Aloe gel extract has a protective effect comparable to glibenclamide against hepatotoxicity produced by diabetes if used in the treatment of type-II diabetes.     

The effect of chondroitin sulfate against CCl4-induced hepatotoxicity

This study was conducted to develop a new biomaterial to be used for an antioxidative drug. In this study, the hepatoprotective effect of chondroitin sulfate (CS) (100 mg/kg and 200 mg/kg body weight) was investigated at the antioxidative enzyme levels of liver total homogenate and mitochondria fraction. And the carbone tetrachloride (CCl(4))-induced rats were used as hepatotoxic models. The CCl(4) induced rat has been widely used as a hepatotoxic model due to its practicality, convenience and cost effectiveness since the generation of free oxygen radicals by CCl(4) injection was proposed as an important causative agent of hepatotoxicity. Malondialdehyde (MDA) levels were determined as well as the activities of superoxide dismutase (SOD), catalase (CAT), reduced-glutathione (GSH), oxidized-glutathione (GSSG) and glutathione peroxidase (GPx) in the liver. In addition, histopathology of liver tissue was investigated. Liver antioxidative enzyme activity was elevated while MDA concentration was decreased in all CS treated animals. The results demonstrated that CS protected oxidative stress in a dose dependent manner. Moreover, inflammation and cirrhosis in liver tissue of CS treated group were significantly decreased. It gave us an impression that CS might be a radical scavenger.     

Hesperidin a flavanoglycone protects against gamma-irradiation induced hepatocellular damage and oxidative stress in Sprague-Dawley rats

Oxidative stress plays a pivotal role in the pathogenesis and progression of gamma-irradiation induced cellular damage and the administration of dietary antioxidants has been suggested to protect against the subsequent tissue damage. Here, we present the data to explore the hepatoprotective and antioxidant effect of hesperidin, a naturally occurring citrus flavanoglycone, against gamma-irradiation induced oxidative damage in the liver of rats. Healthy male Sprague-Dawley rats were exposed to gamma-irradiation (1 Gy, 3 Gy and 5 Gy) and were administered hesperidin (50 mg/kg and 100 mg/kg, b.w, orally) for 7 days post irradiation. The changes in body weight, liver weight, spleen index, serum and liver aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (gamma-GT) and serum ceruloplasmin levels were determined along with differences in the liver histopathology. Liver thiobarbuturic acid reactive substance as an index for lipid peroxidation and the levels of enzymatic antioxidants like superoxide dismutase, catalase, glutathione peroxidase and the status of non-enzymatic antioxidants as an index for oxidative stress were also determined. Exposure to gamma-irradiation resulted in hepatocellular damage in a dose-dependent manner, featuring a significantly decreased body weight and liver weight and higher levels of serum AST, ALT, ALP, LDH and gamma-GT levels and a simultaneous decrease in their levels in the liver tissue. Oxidative stress was evidenced by elevated levels of lipid peroxidation and a decrease in the levels of key enzymatic and non-enzymatic antioxidants in the liver. However, the gamma-irradiation induced toxic effects were dramatically and dose-dependently inhibited by hesperidin treatment as observed by the restoration in the altered levels of the marker enzymes, lipid peroxidation, enzymatic and non-enzymatic antioxidants. The results of the biochemical observations were supported by the histopathological findings. Thus, oral administration of hesperidin was found to offer protection against gamma-irradiation induced hepatocellular damage and oxidative stress in rats, probably by exerting a protective effect against hepatocellular necrosis via its free radical scavenging and membrane stabilizing ability.     

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.     

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.     

Attenuation of oxidative stress in plasma and tissues of rats with experimentally induced hyperthyroidism by caffeic acid phenylethyl ester

Increased oxidative stress with high free radical generation has been described previously in animal models of hyperthyroidism. The present study was designed to investigate the protective effects of caffeic acid phenylethyl ester (CAPE) on oxidative damage in rats with experimentally induced hyperthyroidism. The study was conducted on 32 male Sprague-Dawley rats. The experimental animals were divided into four groups (control, CAPE alone, hyperthyroidism, and hyperthyroidism + CAPE). Hyperthyroidism was induced by intraperitoneal administration of 0.3 mg/kg/day L-thyroxine for 4 weeks. CAPE (10 micro g/kg) was administered intraperitoneally for 4 weeks. At the end of the experimental period, blood samples and various organs (liver, heart and brain) of rats were taken for the determination of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), oxidized glutathione, vitamin C and superoxide dismutase (SOD) levels and concentrations of triiodothyronine (T3), thyroxine (T4) and thyroxine-stimulating hormone (TSH). Our results indicate that TBARS, oxidized glutathione, SOD levels and concentrations of T3 and T4 were higher in plasma and tissues of the hyperthyroid group compared to controls. Vitamin C, GSH and TSH levels were decreased significantly in the hyperthyroid group when compared to the control group. CAPE treatment decreased the elevated TBARS, SOD, T3 and T4 levels and increased the lowered GSH, vitamin C and TSH levels to control levels in rats with hyperthyroidism. In conclusion, our results indicate that CAPE is beneficial as a protective agent against oxidative stress induced by hyperthyroidism in rats. The protection is probably due to multiple mechanisms involving free radical scavenger properties, attenuating lipid peroxidation and increasing the antioxidant status.     

Protective effects of Gingko biloba on thioacetamide-induced fulminant hepatic failure in rats

Gingko biloba (GB) has antioxidant and platelet-activating factor (PAF) antagonistic effects. We investigated the protective effects of GB on thioacetamide (TAA)-induced fulminant hepatic failure in rats. Fulminant hepatic failure was induced in treatment groups by three intraperitoneal (ip) injections of TAA (350 mg/kg) at 24-hour intervals. Treatments with GB (100 mg/kg per day, orally) and N-acetylcysteine (20 mg/kg twice daily, sc) were initiated 48 hours prior to TAA administration. The liver was removed for histopathological examinations. Serum and liver thiobarbituric acid-reactive substance (TBARS) levels were measured for assessment of oxidative stress. Liver necrosis and inflammation scores and serum and liver TBARS levels were significantly higher in the TAA group compared to the control group (P < 0.001, < 0.001, 0.001, < 0.001, respectively). Liver necrosis and inflammation scores and liver TBARS levels were significantly lower in the GB group compared to the TAA group (P < 0.001, < 0.001 and 0.01, respectively). GB ameliorated hepatic damage in TAA-induced fulminant hepatic failure. This may be due to the free radical-scavenging effects of GB.     

In vivo protective effect of protocatechuic acid on tert-butyl hydroperoxide-induced rat hepatotoxicity.

Increasing evidence regarding free-radical generating agents and the inflammatory process suggests that accumulation of reactive oxygen species (ROS) can involve hepatotoxicity. Previously, we found that protocatechuic acid (PCA), a polyphenolic compound from Hibiscus sabdariffa L. possessing free radical-scavenging capacity, protected against oxidative damage induced by tert-butylhydroperoxide (t-BHP) in rat primary hepatocytes. In this study, first PCA was evaluated by its capacity of inhibiting xanthine oxidase (XO) and lipoxygenase (LO) activity in vitro, then it was used to induce hepatotoxicity to assess the antioxidant and anti-inflammatory bioactivity of PCA in vivo. Our investigation showed that pretreatment with PCA (50-100 mg/kg) by gavage for 5 days before a single dose of t-BHP (ip; 0.2 mmol/kg ) significantly lowered serum levels of the hepatic enzyme markers lactate dehydrogenase (LDH) and alanine (ALT) and aspartate (AST) aminotransferase, and reduced oxidative stress of the liver by evaluating malondialdehyde (MDA) and glutathione (GSH). Histopathological evaluation of the rat livers revealed that PCA reduced the incidence of liver lesions, including hepatocyte swelling, leukocyte infiltration, and necrosis induced by t-BHP. In addition, PCA inhibited t-BHP-induced tyrosine phosphorylation, an implication of the activation of a stress signal pathway, in the liver. These results indicate that PCA protects against t-BHP-induced hepatotoxicity by its antioxidant and anti-inflammatory characteristics accompanied by blocking of stress signal transduction.     

Evaluation of free radical-scavenging and anti-oxidant properties of black berry against fluoride toxicity in rats

Oxidative damage to cellular components such as lipids and cell membranes by free radicals and other reactive oxygen species is believed to be associated with the development of degenerative diseases. Fluoride intoxication is associated with oxidative stress and altered anti-oxidant defense mechanism. So the present study was extended to investigate black berry anti-oxidant capacity towards superoxide anion radicals, hydroxyl radicals and nitrite in different organs of fluoride-intoxicated rats. The data indicated that sodium fluoride (10.3 mg/kg bw) administration induced oxidative stress as evidenced by elevated levels of lipid peroxidation and nitric oxide in red blood cells, kidney, testis and brain tissues. Moreover, significantly decreased glutathione level, total anti-oxidant capacity and superoxide dismutase activity were observed in the examined tissues. On the other hand, the induced oxidative stress and the alterations in anti-oxidant system were normalized by the oral administration of black berry juice (1.6 g/kg bw). Therefore it can be concluded that black berry administration could minimize the toxic effects of fluoride indicating its free radical-scavenging and potent anti-oxidant activities.     

Evolution of oxidative stress parameters and response to oral vitamins E and C in streptozotocin-induced diabetic rats

Type I diabetes in humans and streptozotocin (STZ)-induced diabetes in rats has been associated with oxidative stress, but antioxidant therapy has given contradictory results, in part related to the absence of common conditions used to evaluate in-vivo antioxidant properties. This prompted the study of an experimental model of antioxidant therapy in STZ-treated rats. Adult female rats received STZ (50 mgkg(-1)) and were studied 7 or 14 days later. Adipose tissue weight progressively decreased with the time of treatment, whereas plasma triglycerides increased at 7 days, before returning to control values at 14 days after STZ treatment. STZ diabetic rats had increased plasma thiobarbituric acid reacting substances and alpha-tocopherol levels, but the latter variable was decreased when corrected for total lipids. STZ diabetic rats showed a higher GSSG/GSH ratio at Day 14 and lower GSH + GSSG at Day 7 in liver. To evaluate the effect of short-term antioxidant therapy, rats received 5 doses of vitamins C and E over 3 days before being killed on Day 14. Treatment with antioxidants decreased plasma lactic acid and thiobarbituric acid reacting substances, as well as urine 8-isoprostane, and decreased plasma uric acid in controls. Vitamins increased the plasma alpha-tocopherol/lipids ratio only in control rats, although the plasma and liver alpha-tocopherol concentration increased in both groups. STZ diabetic rats showed moderate oxidative stress and treatment with antioxidant vitamins caused a significant change in a selected group of oxidative stress markers, which reflected an improvement in some of the complications associated with this disease. The present experimental conditions can be used as a sensitive experimental model to study the responsiveness of diabetes to other antioxidant interventions.     

吡格列酮改善高脂饮食导致的大鼠肝脏胰岛素抵抗

目的：观察大鼠肝脏中氧化应激以及胰岛素抵抗的发生并探讨吡咯列酮对高脂饮食导致的大鼠肝脏胰岛素抵抗的改善作用。方法：取4周龄雄性SD大鼠,实验分为4组：对照组,高脂组,吡咯列酮组、吡咯列酮＋高脂组。喂养12周后,称体重后断尾法留取空腹血标本,取血测定空腹血糖浓度、血清胰岛素,并计算胰岛素敏感指数;糖原检测试剂盒检测肝脏组织中糖原含量;DHE染色观察肝脏组织中的活性氧自由基水平。结果：正常大鼠的胰岛素敏感指数为-3.47±0.39,高脂饲料喂养12周后,大鼠空腹血糖水平上升,而胰岛素敏感指数降低为-6.29±0.54,吡咯列酮能降低血糖,增加胰岛素敏感指数为-4.54±0.33。蒽酮法的检测结果显示高脂饲料喂养大鼠肝组织糖原含量显著降低到（13.6±2.7）mg/g,吡咯列酮能促进肝脏糖原合成[（19.62±2.88）mg/g]。DHE染色显示肝组织活性氧自由基水平显著增加,吡咯列酮能降低氧化应激水平。结论：高脂饲料喂养SD大鼠胰岛素敏感指数降低,肝组织中活性氧自由基水平显著增加,糖原含量显著降低,吡咯列酮改善高脂饮食导致的大鼠肝脏胰岛素抵抗。     

Beneficial effect of hesperidin on lipopolysaccharide-induced hepatotoxicity

Hesperidin (HDN) is a flavanone glycoside abundantly found in citrus fruits. HDN has been reported to possess significant activities against allergy, haemorrhoids, hormonal disorders and ulcers. Other reported activities include anti-inflammatory, analgesic, antibacterial, antifungal, antiviral, antioxidant and free radical scavenger activity. A potentially important effect of endotoxin is the increased production of reactive oxygen intermediates as O(2)(-), peroxides and nitric oxide. The study reported here show a beneficial effect of HDN in amelioration of endotoxin-induced hepatic dysfunction and oxidative stress in the liver of rats. Hepatotoxicity was induced by administering lipopolysaccharide (LPS), in a single dose of 1mg/kg intraperitoneally to the rats. A marked hepatic dysfunction evident by rise in serum levels of liver enzymes (ALT, AST, ALP) and total bilirubin (p<0.05) was observed. Serum and tissue nitrite levels were also increased. LPS challenge further increased thiobarbituric acid reactive substances (TBARS) levels, whereas glutathione (GSH) content and superoxide dismutase (SOD) activity were decreased in the liver homogenates of the rats showing a marked oxidative stress. HDN administration successfully and dose dependently attenuated these effects of LPS. In conclusion, these findings suggest that HDN attenuates LPS-induced hepatotoxicity possibly by preventing cytotoxic effects of NO and oxygen free radicals.     

Antioxidant status of the hypertrophic heart of Dahl hypertensive rat as a model for evaluation of antioxidants.

Development of hypertension, myocardial hypertrophy and the cardiac antioxidant status of male Dahl salt-sensitive (DSS) genetically hypertensive rats was evaluated and compared to that of normotensive Dahl salt-resistant (DSR) controls. In order to obtain exaggerated and more severe hypertension, half of the animals (10 per group) were Na loaded (8% NaCl diet) for 6 weeks. The myocardial antioxidant status was estimated in tissue homogenates on the basis of tissue glutathione (GSH), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). The results showed that 6 weeks of hypertension resulted in left ventricle myocardial hypertrophy, documented by weight, morphometry and morphological changes. The compromised myocardial antioxidant status of the DSS rats was defined by significantly decreased GSH-Px and glutathione activity (13% and 41%, respectively) as compared to DSR rats. SOD in DSS myocardium was increased by 47% compared to that in DSR myocardium, an effect that is considered a compensatory mechanism to the oxidative stress. All of the above changes were exaggerated by NaCl loading. It was concluded that DSS rats, on either a normal or high NaCl diet, displayed decreased antioxidant capacity, which is most likely genetically determined. Before the Dahl rat can be considered as a suitable model for testing new cardiac antioxidants, a full characterization of the level of cardiac oxygen free radicals is required.