Moringa oleifera Lam. leaf extract prevents early liver injury and restores antioxidant status in mice fed with high-fat diet

Consumption of high-fat diet (HFD) induces nonalcoholic fatty liver disease (NAFLD) and may lead to multiple complications affecting human health. In the present study, effect of Moringa oleifera leaf extract (MoLE) in alleviating HFD induced liver injury in mice has been reported. Liver histology and serum activity of hepatic marker enzymes i.e. aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) have been studied. Lipid peroxidation (LPO), ferric reducing antioxidant power (FRAP) and reduced glutathione (GSH) were also estimated using liver homogenate. Results of the study suggested that MoLE treatment protected HFD-induced liver damage as indicated by histopathology and liver enzyme activity compared to only-HFD fed group (P < 0.05). Interestingly, early signs of HFD-induced fatty liver were also alleviated by MoLE. Moreover, significant increase in endogenous antioxidant parameters and lower lipid peroxidation were found in liver of all MoLE treated groups. Results of the study indicated that MoLE has both preventive as also curative hepatoprotective activity.     

Epicatechin ameliorates ionising radiation-induced oxidative stress in mouse [corrected] liver

The current study was intended to evaluate the hepatoprotective effect of Epicatechin (EC) against radiation-induced oxidative stress, in terms of inflammation and lipid peroxidation. Swiss albino mice were administered with EC (15 mg/kg body weight) for three consecutive days before exposing them to a single dose of 5-Gy (60)Co gamma (γ) irradiation. Mice were necropsied and livers were taken for immunohistochemistry, western blot analysis and biochemical tests for the detection of markers of hepatic oxidative stress. Nuclear translocation of nuclear factor kappa B (NF-κB) and lipid peroxidation were increased whereas the activities of superoxide dismutase (SOD) and catalase (CAT), reduced glutathione (GSH) content and ferric reducing antioxidant power (FRAP) were diminished upon radiation exposure compared to control. Translocation of NF-κB from cytoplasm to nucleus and lipid peroxidation were found to be inhibited whereas an increase in SOD, CAT, GSH and FRAP was observed in the mice treated with EC prior to irradiation. Thus, pre-treatment with EC offers protection against γ-radiation induced hepatic alterations.     

Epicatechin ameliorates ionising radiation-induced oxidative stress in mouse liver

Abstract

The current study was intended to evaluate the hepatoprotective effect of Epicatechin (EC) against radiation-induced oxidative stress, in terms of inflammation and lipid peroxidation. Swiss albino mice were administered with EC (15 mg/kg body weight) for three consecutive days before exposing them to a single dose of 5-Gy ⁶⁰Co gamma (γ) irradiation. Mice were necropsied and livers were taken for immunohistochemistry, western blot analysis and biochemical tests for the detection of markers of hepatic oxidative stress. Nuclear translocation of nuclear factor kappa B (NF-κB) and lipid peroxidation were increased whereas the activities of superoxide dismutase (SOD) and catalase (CAT), reduced glutathione (GSH) content and ferric reducing antioxidant power (FRAP) were diminished upon radiation exposure compared to control. Translocation of NF-κB from cytoplasm to nucleus and lipid peroxidation were found to be inhibited whereas an increase in SOD, CAT, GSH and FRAP was observed in the mice treated with EC prior to irradiation. Thus, pre-treatment with EC offers protection against γ-radiation induced hepatic alterations.     

Modulation of glutathione and antioxidant enzymes by Ocimum sanctum and its role in protection against radiation injury

Aqueous extract (OE) of the leaves of Ocimum sanctum, the Indian holy basil, has been found to protect mouse against radiation lethality and chromosome damage and to possess significant antioxidant activity in vitro. Therefore a study was conducted to see if OE protects against radiation induced lipid peroxidation in liver and to determine the role, if any, of the inherent antioxidant system in radioprotection by OE. Adult Swiss mice were injected intraperitoneally (i.p.) with 10 mg/kg of OE for 5 consecutive days and exposed to 4.5 Gy of gamma radiation 30 min after the last injection. Glutathione (GSH) and the antioxidant enzymes glutathione transferase (GST), reductase (GSRx), peroxidase (GSPx) and superoxide dismutase (SOD), as well as lipid peroxide (LPx) activity were estimated in the liver at 15 min, 30 min, 1, 2, 4 and 8 hr post-treatment. LPx was also studied after treatment with a single dose of 50 mg/kg of OE with/without irradiation. OE itself increased the GSH and enzymes significantly above normal levels whereas radiation significantly reduced all the values. The maximum decline was at 30-60 min for GSH and related enzymes and at 2 hr for SOD. Pretreatment with the extract checked the radiation induced depletion of GSH and all the enzymes and maintained their levels within or above the control range. Radiation significantly increased the lipid peroxidation rate, reaching a maximum value at 2 hr after exposure (approximately 3.5 times that of control). OE pretreatment significantly (P < 0.0001) reduced the lipid peroxidation and accelerated recovery to normal levels. The results indicate that Ocimum extract protects against radiation induced lipid peroxidation and that GSH and the antioxidant enzymes appear to have an important role in the protection.     

Preferential radiation sensitization of prostate cancer in nude mice by nutraceutical antioxidant gamma-tocotrienol

Gamma-tocotrienol (GT) is a member of the vitamin E family. Our preliminary studies indicated that it protected mice from lethal irradiation, so we hypothesized that GT might be a radiation sensitizing agent for tumors. To test this, we induced prostate tumors by injecting PC3 cells into nude BALB/c mice. When the tumors were about 5 mm in diameter, mice were injected subcutaneously with 400 mg/kg gamma-tocotrienol and irradiated 24 h later at the site of the tumor with a dose of 12 Gy (60)Cobalt. Tumor size was monitored for 24 days after radiation. Tumor tissues as well as normal tissues like rectum, kidney, and liver were monitored for lipid peroxidation on day 4 and day 24 after radiation. The results indicated that the size of the tumors was reduced by almost 40%, but only in GT-treated and irradiated mice. In unstimulated and Fe-stimulated lipid peroxidation groups, lipid peroxidation in the tumors from irradiated mice increased to 135% and 150%, respectively, four days after irradiation and 33% and 66% in the same groups, respectively, 24 days after irradiation. In general, lipid peroxidation in the rectum did not increase in GT-treated and irradiated mice, although there was a slight increase in Fe-stimulated lipid peroxidation (29%) four days after irradiation. Unexpectedly, the kidneys were as equally sensitized to lipid peroxidation as the tumors. Liver tissue was protected in the short-term from radiation-induced lipid peroxidation. These studies indicate that the radiotherapy efficacy of prostate cancer can be increased with GT and a pro-oxidant if the kidneys can be shielded.     

S-adenosylmethionine (SAMe) protects against acute alcohol induced hepatotoxicity in mice small star, filled

Although S-Adenosylmethionine (SAMe) has beneficial effects in many hepatic disorders, the effects of SAMe on acute alcohol-induced liver injury are unknown. In the present study, we investigated effects of SAMe on liver injury in mice induced by acute alcohol administration. Male C57BL/6 mice received ethanol (5 g/kg BW) by gavage every 12 hrs for a total of 3 doses. SAMe (5 mg/kg BW) was administrated i.p. once a day for three days before ethanol administration. Subsequent serum ALT level, hepatic lipid peroxidation, enzymatic activity of CYP2E1 and hepatic mitochondrial glutathione levels were measured colorimetrically. Intracellular SAMe concentration was measured by high-performance liquid chromatography (HPLC). Histopathological changes were assessed by H&E staining. Our results showed that acute ethanol administration caused prominent microvesicular steatosis with mild necrosis and an elevation of serum ALT activity. SAMe treatment significantly attenuated the liver injury. In association with the hepatocyte injury, acute alcohol administration induced significant decreases in both hepatic SAMe and mitochondrial GSH levels along with enhanced lipid peroxidation. SAMe treatment attenuated hepatic SAMe and mitochondrial GSH depletion and lipid peroxidation following acute alcohol exposure. These results demonstrate that SAMe protects against the liver injury and attenuates the mitochondrial GSH depletion caused by acute alcohol administration. SAMe may prove to be an effective therapeutic agent in many toxin-induced liver injuries including those induced by alcohol.     

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.     

Differential lipid peroxidative response of rat liver and lung tissues to glutathione depletion induced in vivo by diethyl maleate: effect of the antioxidant flavonoid (+)-cyanidanol-3

The administration of a single dose of diethyl maleate (DEM) to fed rats elicited a drastic decrease in the content of reduced glutathione (GSH) both in liver and lung tissues after 6 h of treatment. Cellular GSH depletion induced by DEM was accompanied by a marked increase in pulmonary lipid peroxidation which was completely abolished by (+)-cyanidanol-3, without changes in the liver. Superoxide dismutase (SOD) activity remained unchanged in both tissues in this situation. Hepatic and pulmonary GSH depletion induced by a second dose of DEM given 24 h later produced a further increase in lung lipid peroxidation and a diminution of pulmonary SOD activity. In this condition, hepatic lipid peroxidation and SOD activity were not altered. These results indicate that lung and liver tissues exhibit a different lipid peroxidative response to chemically-induced GSH depletion.     

Polyunsaturated fatty acids promote 8-hydroxy-2-deoxyguanosine formation through lipid peroxidation under the glutamate-induced GSH depletion in rat glioma cells

It has been reported that glutamate decreased the intracellular glutathione (GSH) concentration and thereby induced cell death in C6 rat glioma cells. Polyunsaturated fatty acids such as arachidonic acid, gamma-linolenic acid, and linoleic acid enhanced lipid peroxidation promoting 8-hydroxy-2'-deoxyguanosine (8-OH-dG) formation under the glutamate-induced GSH-depletion. The enhancement of lipid peroxidation by polyunsaturated fatty acids was species-dependent. Some antioxidants capable of scavenging oxygen and lipid radicals and some iron or copper scavengers inhibited both the lipid peroxidation and the 8-OH-dG formation, consequently protecting against cell death induced by glutamate-induced GSH depletion. These results suggest that GSH depletion caused by glutamate induces lipid peroxidation and consequently 8-OH-dG formation and that polyunsaturated fatty acids enhance lipid peroxidation associated with mediated 8-OH-dG formation through a chain reaction.     

Protection of liposomal lipids against radiation induced oxidative damage.

Liposomes were prepared from phospholipids extracted from biological membranes. A comparison was made between the peroxidation rate in handshake liposomes and in sonicated liposomes. The smaller sonicated liposomes were more vulnerable to peroxidation, probably because of the smaller radius of curvature, which results in a less dense packing of lipid molecules in the bilayer and a facilitated action of water radicals produced by the X-irradiation. High oxygen enhancement ratios were obtained, especially at low dose rates, suggesting the operation of slowly progressing chain reactions initiated by ionizing radiation. Three compounds were tested for their ability to protect the liposomal membranes against lipid peroxidation. The naturally occurring compounds reduced glutathione (GSH) and vitamin E(alpha-T) and the powerful radiation protector cysteamine (MEA). All three molecules could protect the liposomes against peroxidation. The membrane-soluble compound vitamin E was by far the most powerful. About 50 per cent protection was achieved by using 5 X 10(-6) M alpha-T, 10(-4) M GSH and 5 X 10(-4) M MEA. The fatty acid composition of the lipids altered drastically as a result of the irradiation. Arachidonic acid and docosahexanoic acid were the most vulnerable of the fatty acids. Very efficient protection of these polyunsaturated fatty acids could be obtained with relatively low concentrations of vitamin E built into the membranes.     

Role of S-adenosylmethionine on the hepatobiliary homeostasis of glutathione during cyclosporine A treatment

The effects of cyclosporine A (CyA) treatment on the hepatic content and biliary output of reduced (GSH) and oxidized (GSSG) glutathione and lipid peroxidation in the liver, and the ability of S-adenosylmethionine (SAMe) to antagonize the CyA-induced alterations were studied in male Wistar rats. To evaluate the efficacy of SAMe, three CyA and SAMe protocols were used: cotreatment with SAMe plus CyA, pretreatment with SAMe before starting cotreatment, and post-treatment with SAMe after beginning treatment with CyA alone. CyA treatment for one and four weeks depleted liver GSH, decreased the GSH/GSSG ratio and significantly reduced GSH and GSSG biliary concentrations and secretion rates. Additionally, long-term treatment enhanced lipid peroxidation. By contrast, when the rats were treated with CyA plus SAMe using any of the administration protocols, SAMe was seen to be efficient in antagonizing the GSH hepatic depletion, the changes in hepatic GSH/GSSG ratio and the increase induced by CyA in lipid peroxidation. Furthermore, SAMe also abolished the effects of CyA on the biliary secretion rates of GSH and GSSG. The efficacy of SAMe was similar, regardless of the administration protocols used. In conclusion, our results clearly demonstrate that SAMe is good for preventing, antagonizing and reversing the CyA-induced alterations in the hepatobiliary homeostasis of glutathione.     

Mitigating role of lupeol and lupeol linoleate on hepatic lipemic-oxidative injury and lipoprotein peroxidation in experimental hypercholesterolemia

In the present study, the role of pentacyclic triterpenes, lupeol and its ester lupeol linoleate, was studied in relation to hepatic oxidative abnormalities and lipoprotein peroxidation in hypercholesterolemic rats. Hypercholesterolemia was induced in male Wistar rats by feeding them with high cholesterol diet (4% cholesterol + 1% cholic acid; HCD) for 30 days. Pentacyclic triterpenes, lupeol and lupeol linoleate were supplemented (50 mg/kg body wt/day) during the last 15 days. After the experimental period, there was a significant depression in hepatic activities of antioxidant enzymes, SOD (38.39%), CAT (25.03%) and GPx (30.26%) along with a marked fall in the levels of non-enzymic antioxidant molecules GSH (31.39%), vitamin C (46.07%) and vitamin E (42.28%), with a concomitant increase (p<0.001) in lipid peroxidation and in the activities of serum alkaline phosphatase, lactate dehydrogenase and aminotransferases when compared to controls. Treatment with triterpenes decreased lipid peroxidation and reverted the activities of antioxidants (p<0.001 and p<0.01) and marker enzymes to near control. Histopathological findings further confirmed the hepatoprotective nature of triterpenes by showing the normal architecture in treated rats, as against the fatty cellular changes in HCD fed rats. Further, the susceptibility of apo-B containing lipoprotein to oxidation by copper and Fenton’s reagent was increased in in vitro condition in HCD fed rats, whereas the lipoproteins were less susceptible to oxidation in triterpenes treated animals. Therefore, it may be concluded that lupeol and its ester afford protection against the hepatic abnormalities and lipoprotein peroxidation in hypercholesterolemic rats.     

Promoting effects of polyunsaturated fatty acids on chromosomal giant DNA fragmentation associated with cell death induced by glutathione depletion

Glutamate and buthionine sulfoximine (BSO) both reduce intracellular glutathione (GSH) concentration but by different mechanisms, and thereby induce cell death in C6 rat glioma cells. The effects of lipid peroxidation on chromosomal DNA damage during the GSH depletion-induced cell death were assessed. Polyunsaturated fatty acids (PUFA), such as arachidonic acid (AA), gamma-linolenic acid and linoleic acid enhanced lipid peroxidation, induced a loss of membrane integrity and consequently promoted 1-2 Mbp giant DNA fragmentation under both glutamate- and BSO-induced GSH-depletion. Treated C6 cells had 3'-OH termini in their DNA which were recognized by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) analysis. Antioxidants capable of scavenging reactive oxygen species and lipid radicals and iron or copper scavengers inhibited both lipid peroxidation and 1-2 Mbp giant DNA fragmentation, consequently protecting against cell death under GSH depletion. These results suggest that GSH depletion induces lipid peroxidation and leads to 1-2 Mbp giant DNA fragmentation; and that PUFAs can promote giant DNA fragmentation and 3'-OH termini in chromosomal DNA enhancing lipid peroxidation of C6 cells.     

Lipid peroxidation induced by phenylbutazone radicals

Lipid peroxidation was investigated to evaluate the deleterious effect on tissues by phenylbutazone (PB). PB induced lipid peroxidation of microsomes in the presence of horseradish peroxidase and hydrogen peroxide (HRP-H2O2). The lipid peroxidation was completely inhibited by catalase but not by superoxide dismutase. Mannitol and dimethylsulfoxide had no effect. These results indicated no paticipation of superoxide and hydroxyl radical in the lipid peroxidation. Reduced glutathione (GSH) efficiently inhibited the lipid peroxidation. PB radicals emitted electron spin resonance (ESR) signals during the reaction of PB with HRP-H2O2. Microsomes and arachidonic acid strongly diminished the ESR signals, indicating that PB radicals directly react with unsaturated lipids of microsomes to cause thiobarbituric acid reactive substances. GSH sharply diminished the ESR signals of PB radicals, suggesting that GSH scavenges PB radicals to inhibit lipid peroxidation. Also, 2-methyl-2-nitrosopropan strongly inhibited lipid peroxidation. R-Phycoerythrin, a peroxyl radical detector substance, was decomposed by PB with HRP-H2O2. These results suggest that lipid peroxidation of microsomes is induced by PB radicals or peroxyl radicals, or both.     

Tryptophan fluorescence of erythrocyte ghosts following irradiation and Fe2+ initiation of lipid peroxidation

It was shown that under the effect of Fe2+-initiated lipid peroxidation and ionizing radiation tryptophan fluorescence parameters (i.e. intensity and polarization) were subjected to similar changes. Shortly (15 min) after irradiation no changes were observed in the level of products reacting with thiobarbituric acid. It is concluded that the process and products of lipid peroxidation do not markedly contribute to the postirradiation alteration of tryptophan fluorescence. At the same time additional postirradiation damages to proteins can be attributed to activation of lipid peroxidation.     

Identification of protein kinase C inhibitory activity associated with a polypeptide isolated from a phage display system with homology to PCM-1, the pericentriolar material-1 protein

L-arginine may aid in the liver detoxification and may benefit in the treatment of liver disorders such as liver injury. The present study was to investigate the possible protective and curative effects of L-arginine on carbon tetrachloride (CCl(4)) induced hepatotoxicity. Mice received a single dose of CCl(4). L-arginine treatment was given for 6 days prior or post to CCl(4) injection. CCl(4)-intoxication caused marked liver cell necrosis with inflammatory and apoptotic lesions. L-arginine treatment reduced hepatic necrosis and inflammation. CCl(4)-intoxication also enhanced hepatic lipid peroxidation, decreased hepatic GSH level and inhibited the activities of antioxidant enzymes. Pre-treatment and post-treatment with L-arginine decreased lipid peroxidation and restored the antioxidant status to near normal levels. These results suggest that L-arginine administration has hepatoprotective and hepatocurative effects against CCl(4) induced hepatotoxicity in mice.     

Protection by pantothenol and beta-carotene against liver damage produced by low-dose gamma radiation.

Rats were exposed to a total dose of 0.75 Gy of gamma radiation from a 60Co source, receiving three doses of 0.25 Gy at weekly intervals. During two days before each irradiation, the animals received daily intragastric doses of 26 mg pantothenol or 15 mg beta-carotene per kg body mass. The animals were killed after the third irradiation session, and their blood and livers were analyzed. As found previously (Slyshenkov, V.S., Omelyanchik, S.N., Moiseenok, A.G., Trebukhina, R.V. & Wojtczak, L. (1998) Free Radical Biol. Med. 24, 894-899), in livers of animals not supplied with either pantothenol or beta-carotene and killed one hour after the irradiation, a large accumulation of lipid peroxidation products, as conjugated dienes, ketotrienes and thiobarbituric acid-reactive substances, could be observed. The contents of CoA, pantothenic acid, total phospholipids, total glutathione and GSH/GSSG ratio were considerably decreased, whereas the NAD/NADH ratio was increased. All these effects were alleviated in animals supplied with beta-carotene and were completely abolished in animals supplied with pantothenol. In the present paper, we extended our observations of irradiation effects over a period of up to 7 days after the last irradiation session. We found that most of these changes, with the exception of GSH/GSSG ratio, disappeared spontaneously, whereas supplementation with beta-carotene shortened the time required for the normalization of biochemical parameters. In addition, we found that the activities of glutathione reductase, glutathione peroxidase, catalase and NADP-dependent malate (decarboxylating) dehydrogenase ('malic enzyme') in liver were also significantly decreased one hour after irradiation but returned to the normal level within 7 days. Little or no decrease in these activities, already 1 h after the irradiation, could be seen in animals supplemented with either beta-carotene or pantothenol. It is concluded that pantothenol is an excellent radioprotective agent against low-dose gamma radiation.     

Investigation of lipid peroxidation in liposomes induced by heavy ion irradiation

Lipid peroxidation induced by heavy ion irradiation was investigated in 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC) liposomes. Lipid peroxidation was induced using accelerated heavy ions that exhibit linear energy transfer (LET) values between 30 and 15 000 keV/μm and doses up to 100 kGy. With increasing LET, the formation of lipid peroxidation products such as conjugated dienes, lipid hydroperoxides, and thiobarbituric acid-reactive substances decreased. When comparing differential absorption spectra and membrane fluidity following irradiation with heavy ions and x-rays (3 Gy/min), respectively, it is obvious that there are significant differences between the influences of densely and sparsely ionizing radiation on liposomal membranes. Indications for lipid fragmentation could be detected after heavy ion irradiation. Received: 6 March 1997 / Accepted in revised form: 31 March 1998     

Effect of brahma rasayana on antioxidant system after radiation

Oral administration of brahma rasayana (BR; 50 mg/animal for 10 and 30 days) significantly increased the liver antioxidant enzymes such as superoxide dismutase (SOD), catalase(CAT) and tissue and serum levels of reduced glutathione (GSH). Whole body irradiation suppressed the levels of SOD, CAT and GSH. Reduced activity of SOD, CAT and GSH was significantly elevated by treatment with BR after radiation treatment. Similarly radiation exposure induced increase in serum and liver lipid peroxides was significantly reduced by further treatment with BR. The results indicate that BR could ameliorate the oxidative damage produced in the body by radiation and may be useful as an adjuvant during radiation therapy.     

Attenuation of 4-nitroquinoline 1-oxide induced in vitro lipid peroxidation by green tea polyphenols

Lipid peroxidation is believed to play an important role in pathogenesis of diseases. 4-Nitroquiunoline 1-oxide (4-NQO) a potent oral carcinogen, widely used for induction of oral carcinogenesis, was found to induce lipid peroxidation in vivo and in vitro. Green tea contains high content of polyphenols, which are potent antioxidants. Thus green tea polyphenols (GP) can play a protective role in 4-NQO induced in vitro lipid peroxidation. 4-NQO at the concentration of 1.5 mM was found to induce lipid peroxidation in 5% liver homogenate in phosphate buffered saline and extent of lipid peroxidation at the different time intervals 0, 15, 30 and 45 min where studied by assessing parameters such as hydroxyl radical production (OH), thiobarbituric acid reactants (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). It was found that addition of 4-NQO caused an increase in OH and TBARS level and a decrease in activity of SOD, CAT and the levels of GSH. Simultaneous addition of GP 10 mg/ml significantly decreased lipid peroxidation and increased in antioxidant status. Thus, we conclude that GP, a potent antioxidant, was found to nullify 4-NQO induced lipid peroxidation in vitro and 4-NQO acts initially by causing oxidative stress and leads to carcinogenesis.