Resveratrol, a red wine polyphenol, attenuates ethanol-induced oxidative stress in rat liver

The involvement of oxidative stress in the pathogenesis of alcoholic diseases in the liver has been repeatedly confirmed. Resveratrol, a natural phytoalexin present in grape skin and red wine possesses a variety of biological activities including antioxidant. This study was conducted to evaluate whether resveratrol has a preventive effect on the main indicators of hepatic oxidative status as an expression of the cellular damage caused by free radicals, and on antioxidant defence mechanism during chronic ethanol treatment. Wistar rats were treated daily with 35% ethanol solution (3 g/kg/day i.p.) during 6 weeks and fed basal diet or basal diet containing 5 g/kg resveratrol. Control rats were treated with i.p. saline and fed basal diet. Experimentally, chronic ethanol administration leads to hepatotoxicity as monitored by the increase in the level of hepatic marker enzymes and the appearance of fatty change, necrosis, fibrosis and inflammation in liver sections. Ethanol also enhanced the formation of MDA in the liver indicating an increase in lipid peroxidation, a major end-point of oxidative damage, and caused drastic alterations in antioxidant defence systems. Particularly the activities of hepatic superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were found reduced by ethanol treatment while glutathione reductase (GR) activity was unchanged. Dietary supplementation with resveratrol during ethanol treatment inhibited hepatic lipid peroxidation and ameliorated SOD, GPx and CAT activities in the liver. Conclusively, we can suggest that resveratrol could have a beneficial effect in inhibiting the oxidative damage induced by chronic ethanol administration, which was proved by the experiments that we conducted on rats.     

Carnosine prevents the development of oxidative stress under the conditions of toxic action of cadmium

Protective effect of the natural dipeptide carnosine on the antioxidant system of rats under conditions of oxidative stress caused by chronic cadmium administration was investigated. Oxidative status of experimental animals were evaluated based on a number of informative parameters of iron-induced chemiluminescence. It was shown that the introduction of cadmium for 7 days reduces the duration of the latent period of chemiluminescence in the brain, liver, and blood plasma suggesting the depletion of endogenous antioxidant defense. Coexposure to carnosine and cadmium led to significant increase in the level of antioxidant protection in plasma, liver, and brain of animals. Carnosine also prevented the increase of lipid hydroperoxides in the brain and prevented the development of lipid peroxidation content in liver and plasma of animals. Mechanism of the protective effect of carnosine under conditions of oxidative stress induced by cadmium administration was shown on human neuroblastoma SH-SY5Y cell culture. Addition of the cadmium to the incubation medium to a final concentration of 5 μM reduced cell viability of a culture, as was determined by MTT assay; simultaneous addition of carnosine (0.25 mM final concentration) with cadmium resulted in increased cell viability during 24 hours of incubation. Thus, carnosine in a final concentration of 1 mM effectively prevented the development of necrotic lesions of neuroblastoma cells, inhibiting the formation of reactive oxygen species as measured by flow cytometry. The results indicate the ability of carnosine to prevent the development of oxidative stress under the toxic action of cadmium.     

The protection by heme oxygenase‐1 induction against thioacetamide‐induced liver toxicity is associated with changes in arginine and asymmetric dimethylarginine

This study was designed to investigate the role of HO‐1 induction in prevention of thioacetamide (TAA)‐induced oxidative stress, inflammation and liver damage. The changes in hepatic dimethylarginine dimethylaminohydrolase (DDAH) activity as well as plasma arginine and asymmetric dimethylarginine (ADMA) levels were also measured to evaluate nitric oxide (NO) bioavailability. Rats were divided into four groups as control, hemin, TAA and hemin + TAA groups. Hemin (50 mg kg^?1, i.p.) was injected to rats 18 h before TAA treatment to induce HO‐1 enzyme expression. Rats were given TAA (300 mg kg^?1, i.p.) and killed 24 h after treatment. Although TAA treatment produced severe hepatic injury, upregulation of HO‐1 ameliorated TAA‐induced liver damage up to some extent as evidence by decreased serum alanine transaminase, aspartate transaminase and arginase activities and histopathological findings. Induction of HO‐1 stimulated antioxidant system and decreased lipid peroxidation in TAA‐treated rats. Myeloperoxidase activity and inducible NO synthase protein expression were decreased, whereas DDAH activity was increased by hemin injection in TAA‐treated rats. Induction of HO‐1 was associated with increased arginine levels and decreased ADMA levels, being the main determinants of NO production, in plasma of TAA‐treated rats. In conclusion, our results indicate that HO‐1 induction alleviated increased oxidative stress and inflammatory reactions together with deterioration in NO production in TAA‐induced liver damage in rats. Copyright © 2012 John Wiley & Sons, Ltd.     

Effects of shark hepatic stimulator substance on the function and antioxidant capacity of liver mitochondria in an animal model of acute liver injury

This study was carried out to investigate whether shark hepatic stimulator substance （HSS） can prevent acute liver injury and affect mitochondrial function and antioxidant defenses in a rat model of thioacetamide （TAA）-induced liver injury. The acute liver injury was induced by two intraperitoneal injections of TAA （400 mg/kg） in a 24 h interval. In the TAA plus shark HSS group, rats were treated with shark HSS （80 mg/kg） 1 h prior to each TAA injection. In this group, serum liver enzyme activities were significantly lower than those in the TAA group. The mitochondrial respiratory control ratio was improved, and the mitochondrial respiratory enzyme activities were increased in the TAA plus shark HSS group. The mitochondrial antioxidant enzyme activities and glutathione level were higher in the TAA plus shark HSS group than in the TAA group. These results suggest that the protective effect of shark HSS against TAA-induced acute liver injury may be a result of the restoration of the mitochondrial respiratory function and antioxidant defenses and decreased oxygen stress.     

Protection Against Adriamycin-Induced Cardiomyopathy by Carnosine in Rats: Role of Endogenous Antioxidants

The aim of this study was to investigate the effects of carnosine, a biological antioxidant, on the acute cardiac damage induced by a single dose of adriamycin in rats. The experimental design consisted of four groups: Control (saline, i.p.); carnosine (CAR; 10 mg/kg/day, i.p.); adriamycin (ADR; 16 mg/kg on the 14th day, i.p.); carnosine with adriamycin. Carnosine was given 2 weeks before and following adriamycin treatment. Blood samples were collected for analysis of plasma creatine kinase (CK) and plasma antioxidant enzymes, glutathione peroxidase (GSH-Px), Cu, Zn-superoxide dismutase (SOD), and catalase (CAT). The rats were then sacrificed, and the hearts were autopsied for hemodynamic study, ECG, and histopathological examination. Results showed that adriamycin produced evident cardiac damage revealed by hemodynamic change, histological alterations, decreased plasma antioxidant enzymes activities, and increased lipid peroxidation to the control value. Carnosine treatment led to significant attenuation of adriamycin-induced cardiomyopathy revealed by normalization of the LVDP, ST interval, CK, SOD, GSH-Px, CAT, and lipid peroxidation. An increase in oxidative stress and inactivation of SOD, GSH-Px, CAT by a single dose of adriamycin were prevented when carnosine was given 2 weeks before and on the same day adriamycin treatment was administered.     

Comparison of melatonin, vitamin E and L-carnitine in the treatment of neuro- and hepatotoxicity induced by thioacetamide

This study was designed to evaluate and compare the effect of melatonin, vitamin E and L-carnitine on brain and liver oxidative stress and liver damage. Oxidative stress and hepatic failure were produced by a single dose of thioacetamide (TAA) (150 mg kg(-1)) in Wistar rats. A dose of either melatonin (3 mg kg(-1)) vitamin E (20 mg kg(-1) ) or L-carnitine (100 mg kg(-1)) was used. Blood samples were taken from the neck vasculature in order to determine ammonium, blood urea nitrogen (BUN) and liver enzymes. Lipid peroxidation products, glutathione (GSH) content and antioxidative enzymes were determined in cerebral and hepatic homogenates. The results showed a decrease in BUN and in the antioxidant enzymes activities and GSH in the brain and liver. Likewise, TAA induced significant enhancement of lipid peroxidation products levels in both liver and brain, as well as in ammonia values. Melatonin, vitamin E and L-carnitine, although melatonin more significantly, decreased the intensity of the changes produced by the administration of TAA alone. Furthermore melatonin combined with TAA, decreased the ammonia levels and increased the BUN values compared with TAA animals. Also it was more effective than vitamin E or L-carnitine in these actions. These data show the protective effect of these agents, especially melatonin, against oxidative stress and hepatic damage present in fulminant hepatic failure.     

Tamarix gallica ameliorates thioacetamide-induced hepatic oxidative stress and hyperproliferative response in Wistar rats

Tamarix gallica, a hepatic stimulant and tonic, was examined for its ability to inhibit thioacetamide (TAA)-induced hepatic oxidative stress, toxicity and early tumor promotion response in male Wistar rats. TAA (6.6 mmol/kg body wt. i.p) enhanced lipid peroxidation, hydrogen peroxide content, glutathione S-transferase and xanthine oxidase with reduction in the activities of hepatic antioxidant enzymes viz., glutathione peroxidase, superoxide dismutase and caused depletion in the level of hepatic glutathione content. A marked increase in liver damage markers was also observed. TAA treatment also enhanced tumor promotion markers, ornithine decarboxylase (ODC) activity and [3H] thymidine incorporation into hepatic DNA. Pretreatment of rats orally with Tamarix gallica extract (25 and 50 mg/kg body weight) prevented TAA-promoted oxidative stress and toxicity. Prophylaxis with Tamarix gallica significantly reduced the susceptibility of the hepatic microsomal membrane for iron-ascorbate induced lipid peroxidation, H2O2 content, glutathione S-transferase and xanthine oxidase activities. There was also reversal of the elevated levels of liver marker parameters and tumor promotion markers. Our data suggests that Tamarix gallica is a potent chemopreventive agent and may suppress TAA-mediated hepatic oxidative stress, toxicity, and tumor promotion response in rats.     

In vitro and in vivo inhibition of muscle lipid and protein oxidation by carnosine.

Carnosine, a beta-alanyl-L-histidine dipeptide with antioxidant properties is present at high concentrations in skeletal muscle tissue. In this study, we report on the antioxidant activity of carnosine on muscle lipid and protein stability from both in vitro and in vivo experiments. Carnosine inhibited lipid peroxidation and oxidative modification of protein in muscle tissue prepared from rat hind limb homogenates exposed to in vitro Fenton reactant (Fe2+, H2O2)-generated free radicals. The minimum effective concentrations of carnosine for lipid and protein oxidation were 2.5 and 1 mM, respectively. Histidine and beta-alanine, active components of carnosine, showed no individual effect towards inhibiting either lipid or protein oxidation. Skeletal muscle of rats fed a histidine supplemented diet for 13 days exhibited a marked increase in carnosine content with a concomitant reduction in muscle lipid peroxidation and protein carbonyl content in skeletal muscle caused by subjecting rats to a Fe-nitrilotriacetate administration treatment. This significant in vitro result confirms the in vivo antioxidant activity of carnosine for both lipid and protein constituents of muscle under physiological conditions.     

Efficacy of caffeic acid in preventing nickel induced oxidative damage in liver of rats

Nickel (Ni), a major environmental pollutant, is known for its wide toxic manifestations. In the present study caffeic acid (CA), one of the most commonly occurring phenolic acids in fruits, grains and dietary supplements, was evaluated for its protective effect against the Ni induced oxidative damage in liver. In this investigation, Ni (20 mg/kg body weight) was administered intraperitoneally for 20 days to induce toxicity. CA was administered orally (15, 30 and 60 mg/kg body weight) for 20 days with intraperitoneal administration of Ni. Ni induced liver damage was clearly shown by the increased activities of serum hepatic enzymes namely aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) and lactate dehydrogenase (LDH) along with increased elevation of lipid peroxidation indices (thiobarbituric reactive acid substances (TBARS) and lipid hydroperoxides). The toxic effect of Ni was also indicated by significantly decreased levels of enzymatic (superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx) and glutathione S-transferase (GST)) and non-enzymatic antioxidants (glutathione (GSH), vitamin C and vitamin E). CA administered at a dose of 60 mg/kg body weight significantly reversed the activities of hepatic marker enzymes to their near normal levels when compared with other two doses. In addition, CA significantly reduced lipid peroxidation and restored the levels of antioxidant defense in the liver. All these changes were supported by histological observations. The results indicate that CA may be beneficial in ameliorating the Ni induced oxidative damage in the liver of 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.     

Attenuation of oxidative stress and alteration of hepatic tissue ultrastructure by D-pinitol in streptozotocin-induced diabetic rats

Abstract

The present study was aimed to investigate the effect of D-pinitol on hyperglycaemia mediated oxidative stress by analysing the hepatic antioxidant competence, pro-inflammatory cytokines and ultrastructural changes in liver tissues of streptozotocin-induced diabetic rats. Oral administration of D-pinitol (50 mg/kg b.w.) resulted in significant (p < 0.05) attenuation in blood glucose, glycosylated haemoglobin and pro-inflammatory markers such as TNF-α, IL-1β, IL-6, NF-κB p65 unit and NO and significant (p < 0.05) elevation in the plasma insulin level. In addition, D-pinitol instigated a significant escalation in the levels of hepatic tissue non-enzymatic antioxidants and the activities enzymatic antioxidants of diabetic rats with significant (p < 0.05) decrease in lipid peroxides and hydroperoxides formation, thus demonstrating the protective role of D-pinitol on the hepatic tissues from oxidative stress-induced liver damage. These biochemical observations were complemented by histological and ultrastructural examination of liver section. Thus, the present study demonstrates the hepatoprotective nature of D-pinitol by attenuating hyperglycaemia-mediated pro-inflammatory cytokines and oxidative stress.     

Antioxidant protection by β‐selenoamines against thioacetamide‐induced oxidative stress and hepatotoxicity in mice

Thioacetamide (TAA) is a hepatotoxin that rapidly triggers the necrotic process and oxidative stress in the liver. Nevertheless, organic selenium compounds, such as β‐selenoamines, can be used as pharmacological agents to diminish the oxidative damage. Thus, the aim of this study was to investigate the protective effect of the antioxidant β‐selenoamines on TAA‐induced oxidative stress in mice. Here, we observed that a single intraperitoneal injection of TAA (200 mg/kg) dramatically elevated some parameters of oxidative stress, such as lipid peroxidation and reactive oxygen species (ROS) production, as well as depleted cellular antioxidant defenses. In addition, TAA‐induced edema and morphological changes in the liver, which correlate with high serum aspartate and alanine aminotransferase enzyme activities, and a decrease in cell viability. Conversely, a significant reduction in liver lipid peroxidation, ROS production, and edema was observed in animals that received an intraperitoneal injection of β‐selenoamines (15.6 mg/kg) 1 h after TAA administration.     

The effect of dimethyl dimethoxy biphenyl dicarboxylate (DDB) against tamoxifen-induced liver injury in rats: DDB use is curative or protective

Tamoxifen citrate is an anti-estrogenic drug used for the treatment of breast cancer. It showed a degree of hepatic carcinogenesis, when it used for long term as it can decrease the hexose monophosphate shunt and thereby increasing the incidence of oxidative stress in liver rat cells leading to liver injury. In this study, a model of liver injury in female rats was done by intraperitoneal injection of tamoxifen in a dose of 45 mg/kg body weight for 7 successive days. This model produced a state of oxidative stress accompanied with liver injury as noticed by significant declines in the antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase 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 dimethyl dimethoxy biphenyl dicarboxylate (DDB) in a dose of 200 mg/kg body weight daily for 10 successive days, resulted in alleviation of the oxidative stress status of tamoxifen-intoxicated liver injury in rats as observed by significant increments in the antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and catalase) and reduced glutathione concomitant with significant decrements in TBARS and liver transaminases; sGPT and sGOT levels. The administration of DDB before tamoxifen intoxication (as protection) is more little effective than its curative effect against tamoxifen-induced liver injury. The data obtained from this study speculated that DDB can mediate its biochemical effects through the enhancement of the antioxidant enzyme activities and reduced glutathione level as well as decreasing lipid peroxides.     

Effect of vitamin E on monosodium glutamate induced hepatotoxicity and oxidative stress in rats

Monosodium glutamate (MSG), administered to rats (by gavage) at a dose of 0.6 mg/g body weight for 10 days, significantly (P<0.05) induced lipid peroxidation (LPO), decreased reduced glutathione (GSH) level and increased the activities of glutathione-s-transferase (GST), catalase and superoxide dismutase (SOD) in the liver of the animals; these were observed 24 hr after 10 days of administration. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transferase (GGT) were also significantly increased in the serum, on MSG administration. Vitamin E (0.2 mg/g body wt) co-administered with MSG, significantly reduced the LPO, increased the GSH level and decreased the hepatic activities of GST, catalase and SOD. The activities of ALT, AST and GGT in the serum were also significantly reduced. The results showed that MSG at a dose of 0.6 mg/g body wt induced the oxidative stress and hepatotoxicity in rats and vitamin E ameliorated MSG-induced oxidative stress and hepatotoxicity.     

Effects of isoquinoline alkaloid berberine on lipid peroxidation,antioxidant defense system,and liver damage induced by lead acetate in rats

Objectives: Liver is considered a target organ affected by lead toxicity. Oxidative stress is among the mechanisms involved in liver damage. Here we investigated the effects of the natural alkaloid berberine on oxidative stress and hepatotoxicity induced by lead in rats.

Methods: Animals received an aqueous solution of lead acetate (500?mg Pb/l in the drinking water) and/or daily oral gavage of berberine (50?mg/kg) for 8 weeks. Rats were then weighed and used for the biochemical, molecular, and histological evaluations.

Results: Lead-induced oxidative stress, shown by increasing lipid peroxidation along with a concomitant decrease in hepatic levels of thiol groups, total antioxidant capacity, the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase, and reduced versus oxidized glutathione ratio. Berberine corrected all the disturbances in oxidative stress markers induced by lead administration. Berberine also prevented the elevated levels of enzymes (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase) and the decrease in body weight and albumin. The protective effects of berberine were comparable with silymarin. Furthermore, berberine attenuated liver damage, shown by decreased necrosis and inflammatory cell infiltration.

Discussion: Berberine represents a potential therapeutic option against lead-induced hepatotoxicity through inhibiting lipid peroxidation and enhancing antioxidant defenses.

Conclusion: Berberine exerted protective effects on lead-induced oxidative stress and hepatotoxicity in rats.     

Tamarix gallica ameliorates thioacetamide–induced hepatic oxidative stress and hyperproliferative response in Wistar rats

Tamarix gallica, a hepatic stimulant and tonic, was examined for its ability to inhibit thioacetamide (TAA)-induced hepatic oxidative stress, toxicity and early tumor promotion response in male Wistar rats. TAA (6.6 mmol/kg body wt. i.p) enhanced lipid peroxidation, hydrogen peroxide content, glutathione S-transferase and xanthine oxidase with reduction in the activities of hepatic antioxidant enzymes viz., glutathione peroxidase, superoxide dismutase and caused depletion in the level of hepatic glutathione content. A marked increase in liver damage markers was also observed. TAA treatment also enhanced tumor promotion markers, ornithine decarboxylase (ODC) activity and [³H] thymidine incorporation into hepatic DNA. Pretreatment of rats orally with Tamarix gallica extract (25 and 50 mg/kg body weight) prevented TAA-promoted oxidative stress and toxicity. Prophylaxis with Tamarix gallica significantly reduced the susceptibility of the hepatic microsomal membrane for iron-ascorbate induced lipid peroxidation, H₂O₂ content, glutathione S-transferase and xanthine oxidase activities. There was also reversal of the elevated levels of liver marker parameters and tumor promotion markers. Our data suggests that Tamarix gallica is a potent chemopreventive agent and may suppress TAA-mediated hepatic oxidative stress, toxicity, and tumor promotion response in rats.     

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.     

Carnosine ameliorates cognitive deficits in streptozotocin-induced diabetic rats: Possible involved mechanisms

Diabetic patients are at increased risk to develop cognitive deficit and senile dementia. This study was planned to assess the benefits of chronic carnosine administration on prevention of learning and memory deterioration in streptozotocin (STZ)-diabetic rats and to explore some of the involved mechanisms. Rats were divided into 5 groups: i.e., control, carnosine100-treated control, diabetic, and carnosine-treated diabetics (50 and 100 mg/kg). Carnosine was injected i.p. at doses of 50 or 100 mg/kg for 7 weeks, started 1 week after induction of diabetes using streptozotocin. Treatment of diabetic rats with carnosine at a dose of 100 mg/kg at the end of the study lowered serum glucose, improved spatial recognition memory in Y maze, improved retention and recall in elevated plus maze, and prevented reduction of step-through latency in passive avoidance task. Furthermore, carnosine at a dose of 100 mg/kg reduced hippocampal acetylcholinesterase (AChE) activity, lowered lipid peroxidation, and improved superoxide dismutase (SOD) activity and non-enzymatic antioxidant defense element glutathione (GSH), but not activity of catalase. Meanwhile, hippocampal level of nuclear factor-kappaB (NF-κB), tumor necrosis factor α (TNF-α), and glial fibrillary acidic protein (GFAP) decreased and level of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase 1 (HO-1) increased upon treatment of diabetic group with carnosine at a dose of 100 mg/kg. Taken together, chronic carnosine treatment could ameliorate learning and memory disturbances in STZ-diabetic rats through intonation of NF-κB/Nrf2/HO-1 signaling cascade, attenuation of astrogliosis, possible improvement of cholinergic function, and amelioration of oxidative stress and neuroinflammation.     

Protective effects of azelaic acid against high-fat diet-induced oxidative stress in liver, kidney and heart of C57BL/6J mice

Excess fat intake induces hyperinsulinaemia, increases nutrient uptake and lipid accumulation, amplifies ROS generation, establishes oxidative stress and morphological changes leading to tissue injury in the liver, kidney and heart of high-fat diet (HFD)-fed mice. The effect of azelaic acid (AzA), a C9 α,ω-dicarboxylic acid, against HFD-induced oxidative stress was investigated by assaying the activities and levels of antioxidants and oxidative stress markers in the liver, kidney and heart of C57BL/6J mice. Mice were segregated into two groups, one fed standard diet (NC) and the other fed high-fat diet (HFD) for 15 weeks. HFD-fed mice were subjected to intragastric administration of AzA (80 mg/kg BW)/RSG (10 mg/kg BW) during 11-15 weeks. Glucose, insulin, triglycerides, hepatic and nephritic markers were analysed in the plasma and the activity of enzymatic, non-enzymatic antioxidants and lipid peroxidation markers were examined in the plasma/erythrocytes, liver, kidney and heart of normal and experimental mice. We inferred significant decrease in enzymatic and non-enzymatic antioxidants along with significant increase in glucose, insulin, hepatic and nephritic markers, triglycerides and lipid peroxidation markers in HFD-fed mice. Administration of AzA could positively restore the levels of plasma glucose, insulin, triglycerides, hepatic and nephritic markers to near normal. AzA increased the levels of enzymatic and nonenzymatic antioxidants with significant reduction in the levels of lipid peroxidation markers. Histopathological examination of liver, kidney and heart substantiated these results. Hence, we put forward that AzA could counteract the potential injurious effects of HFD-induced oxidative stress in C57BL/6J mice.     

Ameliorative effect of kaempferol,a flavonoid,on oxidative stress in streptozotocin-induced diabetic rats

Abstract

Objective

The aim of the present study was to evaluate the protective effect of kaempferol against oxidative stress in streptozotocin (STZ)-induced diabetic rats.

Methods

Diabetes was induced in male, adult albino rats of the Wistar strain, by intraperitoneal administration of STZ (40 mg/kg body weight (BW)). Kaempferol (100 mg/kg BW) or glibenclamide (600 µg/kg BW) was administered orally once daily for 45 days to normal and STZ-induced diabetic rats.

Results

The STZ-induced diabetic rats showed significantly increased levels of plasma glucose, thiobarbituric acid reactive substances, lipid hydroperoxides, and conjugated dienes in plasma, liver, kidney, and heart whereas they showed significantly decreased level of plasma insulin. The levels of non-enzymic antioxidants (vitamin C, vitamin E, reduced glutathione) in plasma, liver, kidney, and heart and the activities of enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase) in liver, kidney, and heart were significantly decreased in diabetic rats. Administration of kaempferol to diabetic rats was showed brought back in plasma glucose, insulin, lipid peroxidation products, enzymatic, and non-enzymatic antioxidants to near normal.

Conclusion

The present study indicates that kaempferol has a good antioxidant property, as evidenced by its increase of antioxidant status and decrease of lipid peroxidation markers, thus providing protection from the risks of diabetic complications.