Protective effect of Piper betle leaf extract against cadmium-induced oxidative stress and hepatic dysfunction in rats

The present study was undertaken to examine the attenuative effect of Piper betle leaf extract (PBE) against cadmium (Cd) induced oxidative hepatic dysfunction in the liver of rats. Pre-oral supplementation of PBE (200 mg/kg BW) treated rats showed the protective efficacy against Cd induced hepatic oxidative stress. Oral administration of Cd (5 mg/kg BW) for four weeks to rats significantly (P > 0.05) elevated the level of serum hepatic markers such as serum aspartate transaminase (AST), serum alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT), bilirubin (TBRNs), oxidative stress markers viz., thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), protein carbonyls (PC) and conjugated dienes (CD) and significantly (P > 0.05) reduced the enzymatic antioxidants viz., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) and non-enzymatic antioxidants Viz., reduced glutathione (GSH), total sulfhydryls (TSH), vitamin C and vitamin E in the liver. Pre-oral supplementation of PBE (200 mg/kg BW) in Cd intoxicated rats, the altered biochemical indices and pathological changes were recovered significantly (P > 0.05) which showed ameliorative effect of PBE against Cd induced hepatic oxidative stress. From the above findings, we suggested that the pre-administration of P. betle leaf extract exhibited remarkable protective effects against cadmium-induced oxidative hepatic injury in rats.     

Mechanism of adriamycin cardiotoxicity: Evidence for oxidative stress

Adriamycin is a widely used anticancer agent but the cumulative dose-dependent cardiotoxicity severely limits the use of Adriamycin in the treatment of neoplastic diseases. Recent evidence suggests that Adriamycin forms reactive free radical species which may oxidize cellular components and produce the cardiomyopathy. Sulfhydryl donors and antioxidants have been effective in preventing acute Adriamycin cardiotoxicity in animal models presumably by scavenging the free radicals generated by Adriamycin. The sulfhydryl donors, namely cysteamine and N-acetyl cysteine, do not interfere with Adriamycin's antitumor activity. The results from these studies give considerable hope that the chronic cardiotoxicity from Adriamycin may be attenuated in people, thereby givinh additional therapeutic benefit from this antitumor agent.     

Protective effect of Aquilegia vulgaris (L.) on carbon tetrachloride-induced oxidative stress in rats

The ethyl ether extract of A. vulgaris inhibited in vitro microsomal lipid peroxidation (IC50 58.8 microg/ml) and showed moderate ability to scavenge superoxide radicals and to chelate iron ions. The extract (100 mg/kg body weight, po) decreased uninduced and enzymatic microsomal lipid peroxidation in the liver of male rats pretreated with CCl4 (1 ml/kg body weight) by 27 and 40%, respectively. Activity of antioxidant and related enzymes (catalase and glucose-6-phosphate dehydrogenase) inhibited by CCl4 was significantly restored after administration of the extract. The extract itself significantly enhanced superoxide dismutase activity. There was no effect of the extract on hepatic glutathione level and cytochrome P450 content, both were decreased by CCl4. Neither CCl4 nor the tested extract affected activities of NADPH-cytochrome P450 reductase and two monooxygenases, aniline hydroxylase and aminopyrine n-demethylase. It can be concluded that the protective effect of the A. vulgaris extract in CCl4-induced liver injury is mediated by inhibition of microsomal lipid peroxidation and restoring activity of some antioxidant and related enzymes.     

Protective effect of Cassia fistula Linn. on diethylnitrosamine induced hepatocellular damage and oxidative stress in ethanol pretreated rats

Diethylnitrosamine (DEN), found in many commonly consumed foods, is widely reported to induce cancer in animals and humans. The aim of the present study was to investigate the hepatoprotective and antioxidant activities of the leaf extract of the medicinal plant Cassia fistula Linn. against diethylnitrosamine induced liver injury in ethanol pretreated rats. Albino Wistar rats, pretreated with ethanol for 15 days, were administered a single dose of DEN. Thirty days after DEN administration, hepatotocellular damage was observed histologically, along with elevated levels of serum AST, ALT, ALP, LDH, γ-GT and bilirubin and a simultaneous fall in the levels of the marker enzymes in the liver tissue. Liver oxidative stress was confirmed by elevated levels of lipid peroxidation (LPO) and a decrease in enzymic and non-enzymic antioxidants activities. Oral administration of the ethanolic leaf extract (ELE) of Cassia fistula for 30 days to ethanol + DEN treated rats significantly improved the above alterations in the markers of hepatotoxicity and oxidative stress, resulting in the reversal of most of the parameters studied and were comparable to the standard hepatoprotective drug silymarin.     

Epigallocatechin gallate potentially attenuates Fluoride induced oxidative stress mediated cardiotoxicity and dyslipidemia in rats

The present study was undertaken to evaluate the cardioprotective role of (−)-epigallocatechin-gallate (EGCG) against Fluoride (F) induced oxidative stress mediated cardiotoxicity in rats. The animals exposed to F as sodium Fluoride (NaF) (25 mg/kg BW) for 4 weeks exhibited a significant increase in the levels of cardiac troponins T and I (cTnT & I), cardiac serum markers, lipid peroxidative markers and plasma total cholesterol (TC), triglycerides (TG), phospholipids (PL), free fatty acids (FFA), low density lipoprotein cholesterol, very low density lipoprotein cholesterol as well as cardiac lipids profile (TC, TG and FFA) with the significant decrease of high density lipoprotein cholesterol and cardiac phospholipids. F intoxication also decreased the levels of mitochondrial enzymes such as ICDH, SDH, MDH, α-KGDH and NADH in the cardiac tissue of rats. The mitochondrial Ca²⁺ ion level was also significantly reduced along with the significant decrease in the levels of enzymatic and non enzymatic antioxidants. Furthermore, F treatment significantly increased the DNA fragmentation, up regulate cardiac pro-apoptotic markers, inflammatory markers and down-regulate the anti-apoptotic markers in the cardiac tissue. Pre administration of EGCG (40 mg/kg/bw) in F intoxicated rats remarkably recovered all these altered parameters to near normalcy through its antioxidant nature. Thus, results of the present study clearly demonstrated that treatment with EGCG prior to F intoxication has a significant role in protecting F-induced cardiotoxicity and dyslipidemia in rats.     

Protective effect of DL-alpha-lipoic acid on cyclophosphamide induced oxidative cardiac injury

Cyclophosphamide (CP), one of the most widely prescribed antineoplastic drugs could cause a lethal cardiotoxicity. The present study is aimed at evaluating the role of DL-alpha-lipoic acid (LA) in oxidative cardiac damage induced by CP. Adult male Wistar rats were divided into four treatment groups. Two groups received single intraperitoneal injection of CP (200 mg/kg BW) to induce cardiotoxicity, one of these groups received LA treatment (25 mg/kg BW for 10 days). A vehicle treated control group and a LA drug control were also included. Cardiotoxicity, evident from increased activities of serum creatine phosphokinase, lactate dehydrogenase, aspartate transaminase and alanine transaminase in CP administered rats, was reversed by LA treatment. CP administered rats showed abnormal levels of enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase) and non-enzymic antioxidants (glutathione, vitamin C and vitamin E) along with high malondialdehyde levels. However, normalized lipid peroxidation and antioxidant defenses were reported in the LA treated rats. These findings highlight the efficacy of LA as a cytoprotectant in CP induced cardiotoxicity.     

Protective effect of Lycium barbarum polysaccharides on streptozotocin-induced oxidative stress in rats

Fruit from Lycium barbarum L. in the family Solanaceae is well-known in traditional Chinese herbal medicine. Lycium barbarum polysaccharides (LBP) have been identified as one of the active ingredients responsible for its biological activities. We isolated polysaccharides from dried Lycium barbarum fruits by boiling water extraction. In the study, 50 animals were divided into two groups: a nondiabetic control (n = 10) and a diabetic group (n = 40). Diabetes was induced by a single injection of streptozotocin (50 mg/kg BW; Sigma, USA) freshly dissolved in a 0.1 mol/L citrate buffer (pH 4.5) into the intraperitonium. The normal control rats and the untreated diabetic control rats were only injected with the citrate buffer. Treated diabetic rats were administrated with LBP in drinking water through oral gavage for 30 days. At the end of experiment, oxidative indice in blood, liver and kidney of all groups were examined. The results show that administration of LBP can restore abnormal oxidative indice near normal levels. Therefore, we may assume that LBP is effective in the protection of liver and kidney tissue from the damage of STZ-induced diabetic rats and that the LBP may be of use as a antihyperglycemia agent.     

Loperamide‐induced cardiotoxicity in rats: Evidence from cardiac and oxidative stress biomarkers

At therapeutic dose, loperamide is a safe over‐the‐counter antidiarrheal drug but could induce cardiotoxic effect at a supratherapeutic dose. In this study, we use cardiac and oxidative biomarkers to evaluate loperamide‐induced cardiotoxicity in rats. Rats were orally gavaged with 1.5, 3, or 6 mg/kg body weight (BW) of loperamide hydrochloride for 7 days. The results after 7 days administration of loperamide, revealed dose‐dependent increase (P < 0.05) in aspartate aminotransferase, lactate dehydrogenase, creatine kinase‐MB, and serum concentration of cardiac troponin I, total homocysteine, and nitric oxide. A 50% decrease in antioxidant enzymes activity was observed at 6 mg/kg BW. Furthermore, malondialdehyde and fragmented DNA also increased significantly in the heart of the treatment groups. Loperamide provoked cardiotoxicity through oxidative stress, lipid peroxidation, and DNA fragmentation in rats. This study has provided a possible biochemical explanation for the reported cardiotoxicity induced by loperamide overdose.     

Antioxidant efficacy of black pepper (Piper nigrum L.) and piperine in rats with high fat diet induced oxidative stress

The present study was aimed to explore the effect of black pepper (Piper nigrum L.) on tissue lipid peroxidation, enzymic and non-enzymic antioxidants in rats fed a high-fat diet. Thirty male Wistar rats (95-115 g) were divided into 5 groups. They were fed standard pellet diet, high-fat diet (20% coconut oil, 2% cholesterol and 0.125% bile salts), high-fat diet plus black pepper (0.25 g or 0.5 g/kg body weight), high-fat diet plus piperine (0.02 g/kg body weight) for a period of 10 weeks. Significantly elevated levels of thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and significantly lowered activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) in the liver, heart, kidney, intestine and aorta were observed in rats fed the high fat diet as compared to the control rats. Simultaneous supplementation with black pepper or piperine lowered TBARS and CD levels and maintained SOD, CAT, GPx, GST, and GSH levels to near those of control rats. The data indicate that supplementation with black pepper or the active principle of black pepper, piperine, can reduce high-fat diet induced oxidative stress to the cells.     

Protective effect of Argan oil on mitochondrial function and oxidative stress against acrylamide-induced liver and kidney injury in rats

Abstract

Context

Acrylamide (ACR) is now a risk for general public health. Argan oil (AO) is harvested from the fruits of Argania spinosa and its rich source of antioxidant and phenolic compounds.     

Protective effect of zinc on liver injury induced byd-galactosamine in rats

The protective effects of zinc on liver injury induced byd-galactosamine (GalN) were investigated in rats in vivo and in vitro. Zinc supplementation (50 mg/kg/d) for 5 d of rats treated with GalN (1.5 g/kg, ip) could reduce their mortality rate, restore liver pathomorphological changes, maintain zinc content, inhibit the lipid peroxidation, hasten the protein synthesis, and improve liver function. In vitro, zinc supplement could abate the death of GalN-intoxicated hepatocytes, decrease malonaldehyde (MDA) content, and maintain reduced glutathione (GSH). It is concluded that zinc has protective effects on GalN-induced liver damage. Its effects may be owing to inhibition of lipid peroxidation and hastening of protein syntheses.     

Protective effect of alpha-tocopherol on oxidative stress in experimental pulmonary fibrosis in rats

The study was undertaken to investigate the influence of alpha-tocopherol (vitamin E) on malondialdehyde (MDA) and glutathione (GSH) levels and catalase (CAT) activity in lung of rats with bleomycin-induced pulmonary fibrosis (PF). Fourteen Wistar-albino rats were randomly divided into two groups of seven animals each. The first group was treated intra-tracheally with bleomycin hydrochloride (BM group); the second group was also instilled with BM but received injections of alpha-tocopherol twice a week (BM + E group). The third group was treated in the same manner with saline solution only, acting as controls (C). There were decreases in GSH level and CAT activity while an increase in MDA level in BM group was found compared to the control group (p < 0.05). Vitamin E had a regulator effect on these parameters. After administration of alpha-tocopherol, the increase in GSH level and CAT activity and the decrease in MDA level were seen in BM + E group compared to BM group (p < 0.05). Distinct histopathological changes were found in the BM group compared to the untreated rats. Less severe fibrotic lesions were also observed in the BM + E group. The results show that vitamin E is effective on the prevention of BM-induced PF, as indicated by differences in the lung levels of oxidants and antioxidants.     

Protective effect of sulfated Achyranthes bidentata polysaccharides on streptozotocin-induced oxidative stress in rats

Sulfated Achyranthes bidentata polysaccharide (SAbP) is derived from traditional Chinese herbal medicine A. bidentata polysaccharide (AbP) by chemical modification. The present study was designed to determine the possible protective effect of SAbP against oxidative damage in streptozotocin (STZ)-treated diabetic rats. Results showed SAbP significantly reduced blood glucose level and malondialdehyde (MDA) concentration in diabetic rats. The activities of GPx and SOD were increased in diabetic rats. But the effects of AbP on blood glucose, MDA concentration and antioxidant enzymes activities are not obvious as SAbP. Therefore, we postulate that SAbP has a better protective effect in diabetes than AbP and this may be attributed to its antioxidative potential.     

Protective effect of acetyl-L-carnitine against oxidative stress induced by antiretroviral drugs

Both HIV infection per se and antiretroviral drugs might contribute to oxidative stress and mitochondrial dysfunctions. In this study we assess zidovudine, stavudine and didanosine on U937 and CEM cell lines. All these drugs induced apoptosis and increased intracellular hydrogen peroxide but not superoxide anions. The addition of acetyl-l-carnitine (ALC) was able to prevent the pro-oxidant effect of the drugs tested. Supplementation with ALC, deficient in certain cohorts of HIV-infected individuals, especially on high active antiretroviral therapy regimen, has been associated with favourable effects. These data suggest that one of these effects could be a direct anti-oxidant action.     

Protective effect of aminoguanidine against oxidative stress and bladder injury in cyclophosphamide‐induced hemorrhagic cystitis in rat

Cyclophosphamide (CP) is an antineoplastic agent that is used for the treatment of many neoplastic diseases. Hemorrhagic cystitis (HC) is a major dose limiting side effect of CP. Recent studies show that aminogaunidine, an inhibitor of inducible nitric oxide synthase is a potent antioxidant and prevents changes caused by oxidative stress such as depletion of antioxidant activity and tissue injury. The purpose of the study is to investigate the effect of aminoguanidine on parameters of oxidative stress, antioxidant enzymes and bladder injury caused by CP. Adult male rats were randomly divided into four groups. Control rats were administered saline; the AG control group received 200 mg/kg body wt of aminoguanidine; The CP group received a single injection of CP at the dose of 150 mg/kg body wt intraperitoneally. The CP + AG group received aminoguanidine (200 mg/kg body wt) intraperitoneally 1 h before the administration of CP. The rats were sacrificed 16 h after CP/saline administration. The bladder was used for light microscopic studies and biochemical studies. The markers of oxidative damage including protein carbonyl content, protein thiol, malondialdehyde and conjugated dienes were assayed in the homogenates along with the activities of the antioxidant enzymes, superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase and glutathione S transferase. In the bladders of CP treated rats edema of lamina propria with epithelial and sub‐epithelial hemorrhage was seen. All the parameters of oxidative stress that were studied were significantly elevated in the bladders of CP treated rats. The activities of the antioxidant enzymes were significantly lowered in the bladders of CP treated rats. Aminoguanidine pretreatment prevented CP‐induced oxidative stress, decrease in the activities of anti‐oxidant enzymes and reduced bladder damage. The results of the present study suggest the antioxidant role for aminoguanidine in CP‐induced bladder damage. Copyright © 2008 John Wiley & Sons, Ltd.     

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.     

Isolation and Characterization of Antidermatophytic Bioactive Molecules from Piper longum L. Leaves

Piper longum L. (Piperaceae) commonly known as “long pepper” is a well known medicinal plant in ayurveda. Different parts of this plant, such as root, seed, fruit, whole plant etc. are used traditionally in various ailments. Here we have investigated the antidermatophytic activity of sequentially extracted petroleum ether, chloroform, methanol and water extracts from P. longum leaf against Trichophytonmentagrophytes, T. rubrum, T. tonsurans, Microsporum fulvum and M. gypseum. Better activity of chloroform and methanol extracts was observed. The chloroform extract was selected for further study and the MIC value was recorded as 5.0 mg ml⁻¹ against the test organisms. In the chloroform extract, tannins and phenolic compounds were detected. Further activity-guided fractionation of chloroform extract by silica gel column chromatography yielded nine major fractions. Among these, fraction-1, 4, 5 and 7 showed higher antidermatophytic activity. Fraction-4 on further purification by repeated column chromatography yielded a potential antidermatophytic fraction showing MIC value of 0.625 mg ml⁻¹ against T. mentagrophytes and T. rubrum as determined by broth microdilution method. The major compounds were identified as 1,2-benzenedicarboxylic acid, bis(2-ethylhexyl) ester (C₂₄H₃₈O₄] (41.45 %), 2,2-dimethoxybutane (C₆H₁₄O₂] (13.6 %) and β-myrcene (C₁₀H₁₆) (6.75 %) based on GC–MS data.     

Protective effects of dietary nasunin on paraquat-induced oxidative stress in rats.

The preventive effects of nasunin (delphinidin-3-[4-p-coumaroyl-rhamnosyl(1-->6)glucosid e]-5-glucoside) on paraquat-induced oxidative stress were determined in rats. Decreased food intake and body weight gain and increased lung weight by feeding the rats a diet containing paraquat were clearly suppressed by supplementing nasunin to the paraquat diet. Paraquat feeding increased the concentration of thiobarbituric acid-reactive substances (TBARS) in liver lipids and the atherogenic index, and decreased the liver triacylglycerol level. These effects were also suppressed by supplementing nasunin to the paraquat diet. In addition, catalase activity in the liver mitochondrial fraction was markedly decreased by feeding the paraquat diet, this decrease being partially suppressed by supplementing the paraquat diet with nasunin. These results suggest that nasunin acted preventively against the oxidative stress in vivo that may have been due to active oxygen species formed through the action of paraquat.