Ferulic acid influences hepatic expression pattern of matrix metalloproteinases during alcohol and PUFA induced toxicity.

BACKGROUND AND OBJECTIVES: Alcoholic fibrosis and its end stage cirrhosis represent a major health problem worldwide. Liver fibrosis occurs when the rate of matrix synthesis exceeds matrix degradation. The degree of matrix remodeling depends on the ratio of active matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The objective of the present work was to study the influence of ferulic acid, a polyphenolic compound, on the expression of MMPs and TIMPs during alcohol and heated polyunsaturated fatty acid (delta PUFA) induced liver toxicity in male albino Wistar rats. MATERIALS AND METHODS: The levels of collagen, the activity of MMPs, the activity of TIMPs, the expression pattern of MMP were analyzed in liver. RESULTS: The matrix metalloproteinase expression was found to be significantly increased in alcohol as well as delta PUFA treated rats and significantly decreased in alcohol + delta PUFA treated rats. The levels of TIMPs and the collagen were significantly increased in alcohol, delta PUFA and alcohol + delta PUFA groups. Administration of ferulic acid significantly decreased the levels of collagen, TIMPs and positively modulated the expression of MMPs. CONCLUSIONS: Ferulic acid influences MMPs, TIMPs expression and effectively protects liver against alcohol and DPUFA induced liver fibrosis.

Antihyperlipidemic effect of chlorogenic acid and tetrahydrocurcumin in rats subjected to diabetogenic agents.

Diabetes mellitus is associated with dyslipidemia, which is a significant risk factor for cardiovascular complications. The present study was carried out to evaluate the effects of tetrahydrocurcumin (THC) and chlorogenic acid (CGA) alone and in combination on alterations in lipids, lipoproteins and enzymes involved in lipid metabolism in streptozotocin (STZ)-nicotinamide (NA)-induced type 2 diabetic rats. A significant (p<0.05) increase in the concentrations of plasma and tissue (liver and kidney) lipids (cholesterol, triglycerides (TGs), free fatty acids (FFAs) and phospholipids (PLs)) and low density and very low-density lipoproteins (LDL and VLDL), and a decrease in the concentration of high-density lipoproteins (HDL) were noticed in STZ administered diabetic rats. In addition, the activity of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase increased significantly (p<0.05) in the liver and kidney whereas the activities of lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) were decreased significantly (p<0.05) in the plasma of diabetic rats. Combined administration of CGA (5mg/kg b.w.) and THC (80mg/kg b.w.) for 45 days remarkably reduced the STZ-induced changes in lipids, lipoproteins and lipid metabolising enzymes when compared to the effects of CGA or THC alone in diabetic rats. These results indicate that combination of THC and CGA can potentially ameliorate lipid abnormalities in experimental type 2 diabetes.

Chemopreventive efficacy of curcumin and piperine during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis.

INTRODUCTION: Oral carcinoma accounts for 40-50 percent of all cancers in India. Tobacco chewing, smoking and alcohol consumption are the major risk factors associated with the high incidence of oral cancer in India. Our aim was to investigate the chemopreventive potential of curcumin and piperine during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. METHODS: Oral squamous cell carcinoma was developed in the buccal pouch of Syrian golden hamsters, by painting them with 0.5 percent DMBA in liquid paraffin, three times a week for 14 weeks. The tumour incidence, tumour volume and burden were determined in the buccal pouches. The status of phase II detoxification agents, lipid peroxidation and antioxidants were estimated by specific colorimetric methods. RESULTS: We observed 100 percent tumour formation in DMBA-alone painted hamsters. Disturbances in the status of lipid peroxidation, antioxidants and phase II detoxification agents were noticed in DMBA-alone painted hamsters. Oral administration of curcumin (80 mg/kg body weight) and piperine (50 mg/kg body weight) to DMBA-painted hamsters on alternate days to DMBA painting for 14 weeks completely prevented the formation of oral carcinoma. Also, curcumin and piperine restored the status of lipid peroxidation, antioxidants and detoxifying agents in DMBA-painted hamsters. CONCLUSION: The chemopreventive efficacy of curcumin and piperine is probably due to their antilipidperoxidative and antioxidant potential as well as their modulating effect on the carcinogen detoxification process.

In vitro radical scavanging activities of Chrysaora quinquecirrha nematocyst venom.

The venom of Chrysaora quinquecirrha (sea nettle) contains several toxins that have bioactivity in mammals. In our study we aimed to extract proteins from Chrysaora quinquecirrha and to test the antioxidant potential of both crude protein and purified fractions. Proteins extracted from sea nettle nematocyst venom were purified through Sephadex G-100 column chromatography. The molecular weight of purified proteins was determined by gel filtration and SDS-PAGE and was found to be 105, 65, and 9 kDa for Frc-1, Frc-2, Frc-3, respectively. The in vitro antioxidant potential of Chrysaora quinquecirrha was evaluated in different systems viz. radical scavenging activity by DPPH reduction, superoxide radical scavenging activity in PMS/NADH-NBT system, hydroxyl radical by Fe(3+)-Ascorbate-EDTA-H2O2 system and nitric oxide (NO) radical scavenging activity in sodium nitroprusside/Greiss reagent system. Frc-3 displayed the maximal antioxidant activity and found to have different levels of antioxidant properties in the models tested. In scavenging hydroxyl radicals, its activity was intense (IC(50) = 50.8 µg/mL) while in scavenging NO radical, it was moderate (IC(50) = 381.4 µg/mL).

Antioxidant activity of an aminothiazole compound: possible mechanisms.

Oceans are among the richest natural sources of many bioactive compounds. Several of these compounds have shown pharmacological activities for many diseases. Dendrodoine (5-[(3-N-dimethylamino)-1,2,4-thiadiazolyl]-3-indanyl methanone) is an alkaloid extracted from the marine tunicate Dendrodoa grossularia. Aminothiazoles have a wide range of biological activities including anti-tumor and antioxidant properties. The aim of our study was to examine the antioxidant ability of an aminothiazole derivative, dendrodoine analogue (DA) [(4-amino-5-benzoyl-2-(4-methoxy phenylamino) thiazole] which has been chemically synthesized and is similar to dendrodoine. In all the biochemical assays used in our study, corresponding to different levels of protection, DA showed concentration dependent antioxidant ability. DA (3.07 microM) showed an ability to inhibit 2,2'-azobis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) radical formation to the extent of 0.17 microM of 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). The ferric complex reducing ability of 3.07 microM DA was equivalent to 110 microM Trolox. 3.07 microM DA gave 84% protection against deoxyribose degradation, a measure of hydroxyl radical scavenging. DA also has an ability to scavenge NO radical, 3.07 microM DA effecting 20% scavenging. Concentration dependent inhibition of lipid peroxidation and protein oxidation induced by 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) and ascorbate-Fe2+ was observed with low concentrations of DA (1.5-3.07 microM). Mechanistic studies using pulse radiolysis revealed that DA scavenges peroxyl radicals with a bimolecular rate constant of 3 x 10(8)M(-1)s(-1). Moreover, the initially formed nitrogen-centered radical gets transformed into sulfur-centered radical before furnishing any final product. Our results indicated that DA can be a free radical scavenger and potential antioxidant for future application.

Resveratrol enhances GLUT-4 translocation to the caveolar lipid raft fractions through AMPK/Akt/eNOS signalling pathway in diabetic myocardium.

Homeostasis of blood glucose by insulin involves stimulation of glucose uptake by translocation of glucose transporter Glut-4 from intracellular pool to the caveolar membrane system. In this study we examined resveratrol (RSV)-mediated Glut-4 translocation in the streptozotocin (STZ)-induced diabetic myocardium. The rats were randomized into three groups: Control (Con), Diabetes Mellitus (DM) (STZ 65 mg/kg b.w., i.p.) & DM+RSV (2.5 mg/kg b.wt. for 2 weeks orally) (RSV). Isolated rat hearts were used as per the experimental model. RSV induced glucose uptake was observed in vitro with H9c2 cardiac myoblast cells. Decreased blood glucose level was observed after 30 days (375 mg/dl) in RSV-treated rats when compared to DM (587 mg/dl). Treatment with RSV demonstrated increased Adenosine Mono Phosphate Kinase (AMPK) phosphorylation compared to DM. Lipid raft fractions demonstrated decreased expression of Glut-4, Cav-3 (0.4, 0.6-fold) in DM which was increased to 0.75- and 1.1-fold on RSV treatment as compared to control. Increased Cav-1 expression (1.4-fold) in DM was reduced to 0.7-fold on RSV treatment. Increased phosphorylation of endothelial Nitric Oxide Synthase (eNOS) & Akt was also observed in RSV compared to DM (P<0.05). Confocal microscopy and coimmunoprecipitation studies demonstrated decreased association of Glut-4/Cav-3 and increased association of Cav-1/eNOS in DM as compared to control and converse results were obtained on RSV treatment. Our results suggests that the effect of RSV is non-insulin dependent and triggers some of the similar intracellular insulin signalling components in myocardium such as eNOS, Akt through AMPK pathway and also by regulating the caveolin-1 and caveolin-3 status that might play an essential role in Glut-4 translocation and glucose uptake in STZ- induced type-1 diabetic myocardium.

Heterozygous disruption of Flk-1 receptor leads to myocardial ischaemia reperfusion injury in mice: application of affymetrix gene chip analysis.

This study addresses an important clinical issue by identifying potential candidates of vascular endothelial growth factor (VEGF) signalling through the Flk-1 receptor that trigger cardioprotective signals under ischaemic stress. Isolated working mouse hearts of both wild-type (WT) and Flk-1(+/-) were subjected to global ischaemia (I) for 30 min. followed by 2 hrs of reperfusion (R). Flk-1(+/-) myocardium displayed almost 50% reduction in Flk-1 mRNA as examined by quantitative real-time RT-PCR at the baseline level. Flk-1(+/-) mouse hearts displayed reduction in left ventricular functional recovery throughout reperfusion (dp/dt 605 versus 884), after 2 hrs (P<0.05). Coronary (1.9 versus 2.4 ml) and aortic flow (AF) (0.16 versus 1.2 ml) were reduced in Flk-1(+/-) after 2 hrs of reperfusion. In addition, increased infarct size (38.4%versus 28.41%, P<0.05) and apoptotic cardiomyocytes (495 versus 213) were observed in Flk-1(+/-) knockout (KO) mice. We also examined whether ischaemic preconditioning (PC), a novel method to induce cardioprotection against ischaemia reperfusion injury, through stimulating the VEGF signalling pathway might function in Flk-1(+/-) mice. We found that knocking down Flk-1 resulted in significant reduction in the cardioprotective effect by PC compared to WT. Affymetrix gene chip analysis demonstrated down-regulation of important genes after IR and preconditioning followed by ischaemia reperfusion in Flk-1(+/-) mice compared to WT. To get insight into the underlying molecular pathways involved in ischaemic PC, we determined the distinct and overlapping biological processes using Ingenuity pathway analysis tool. Independent evidence at the mRNA level supporting the Affymetrix results were validated using real-time RT-PCR for selected down-regulated genes, which are thought to play important roles in cardioprotection after ischaemic insult. In summary, our data indicated for the first time that ischaemic PC modifies genomic responses in heterozygous VEGFR-2/Flk-1 KO mice and abolishes its cardioprotective effect on ischaemic myocardium.

Effect of ellagic acid, a natural polyphenol, on alcohol-induced prooxidant and antioxidant imbalance: a drug dose dependent study.

INTRODUCTION: Alcohol abuse, alcohol intolerance and other alcohol-related disabilities are some of the most challenging public health problems. Alcohol, by its property of generating free radicals, causes severe damage to the membrane and affects almost all organs of the human body. Ellagic acid (EA), a natural polyphenolic compound found in fruits and nuts, possess several biological properties. Our aim was to investigate, in vivo, the antioxidant potential of ellagic acid against oxidative stress induced by alcohol intoxication. METHODS: Female albino Wistar rats were used for the study. The toxicity was induced by administering 20 percent alcohol orally (7.9 g/kg body weight) for 45 days. Rats were treated with EA at three different doses (30, 60 and 90 mg/kg body weight) via intragastric intubations. The antioxidant property of EA was studied by assessing the activities of liver marker enzymes (gamma-glutamyl transferase and alkaline phosphatase), superoxide dismutase and catalase and the levels of vitamin E, vitamin C and reduced glutathione, nitric oxide (NO), protein carbonyl content (PCC), thiobarbituric acid reactive substances (TBARS) and hydroperoxides. RESULTS: Oxidative stress was effectively modulated by EA co-administration. EA significantly improved the status of antioxidants and decreased TBARS, hydroperoxides, NO, PCC and liver marker enzymes at the dose of 60 mg/kg body weight when compared with the alcohol-treated group. CONCLUSION: The study provides the antioxidant and cytoprotective properties of EA at a dose of 60 mg/kg body weight against oxidative stress induced by alcohol.

Comparative effects of curcumin and its synthetic analogue on tissue lipid peroxidation and antioxidant status during nicotine-induced toxicity.

INTRODUCTION: Tobacco consumption is one of the leading preventable causes of death and disease worldwide. Nicotine, a major toxic component of tobacco, has been identified as an important risk factor for lung-related diseases. Increasing evidence demonstrates that oxidative stress plays a crucial aetiological role in the development of lung-related diseases. The present study aims at evaluating the protective role of curcumin and a synthetic analogue of curcumin (BDMC-A) on nicotine-induced oxidative stress. METHODS: Male albino rats of Wistar strain were used for the experimental study. Lung toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5 mg/kg body weight (five days a week, for 22 weeks) and curcuminoids were given simultaneously by intragastric intubation for 22 weeks. Measurement of lipid peroxidation indices, thiobarbituric acid reactive substances and hydroperoxides, nitric oxide and antioxidants, such as superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, vitamin E and vitamin C, were used as biomarkers for testing the antioxidant potential of the drugs. RESULTS: Oxidative stress, as evidenced by lipid peroxidation indices, was significantly increased in nicotine-treated groups. Administration of curcumin and BDMC-A abrogated this effect. The antioxidant status which was decreased in nicotine was effectively modulated by both curcumin and BDMC-A treatment. However, the reduction in oxidative stress was more pronounced in BDMC-A treatment groups compared to those treated with curcumin. CONCLUSION: The present study suggests that BDMC-A exerts its protective effect by modulating the extent of lipid peroxidation and augmenting the antioxidant defence system.

Lycopene as a natural protector against gamma-radiation induced DNA damage, lipid peroxidation and antioxidant status in primary culture of isolated rat hepatocytes in vitro.

The present study was designed to evaluate the radioprotective effect of lycopene, a naturally occurring dietary carotenoid, on gamma-radiation induced toxicity in cultured rat hepatocytes. The cellular changes were estimated using lipid peroxidative indices like thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), ceruloplasmin, vitamins A, E, C and uric acid. The DNA damage was analysed by single cell gel electrophoresis (comet assay). The increase in the severity of DNA damage was observed with the increase in gamma-radiation dose (1, 2 and 4 Gy) in cultured rat hepatocytes. TBARS were increased significantly whereas the levels of GSH, vitamins C, E and A, ceruloplasmin, uric acid and antioxidant enzymes were significantly decreased in gamma-irradiated groups. The maximum damage to hepatocytes was observed at 4 Gy irradiation. Pretreatment with lycopene (1.86, 9.31 and 18.62 microM) showed a significant decrease in the levels of TBARS and DNA damage. The antioxidant enzymes increased significantly along with the levels of GSH, vitamins A, E, C, uric acid and ceruloplasmin. The maximum protection of hepatocytes was observed at 9.31 muM of lycopene pretreatment. Thus, our results show that pretreatment with lycopene offers protection against gamma-radiation induced cellular damage and can be developed as an effective radioprotector during radiotherapy.

Modulatory effects of curcumin on γ-radiation-induced cellular damage in primary culture of isolated rat hepatocytes.

Ionizing radiation is known to induce oxidative stress through generation of reactive oxygen species (ROS) resulting in imbalance of the pro-oxidant and antioxidant in the cells, which is suggested to culminate in cell death. The present work was aimed to evaluate the radioprotective effect of curcumin, a yellow pigment of turmeric on γ-radiation-induced toxicity in primary cultures of isolated rat hepatocytes. Hepatocytes were isolated from the liver of rats by collagenase perfusion. The cellular changes were estimated using lipid peroxidative indices like thiobarbituric acid reactive substances (TBARS), the antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH), ceruloplasmin, vitamins A, E and C and uric acid. The comet assay is a sensitive and rapid technique for quantifying and analyzing DNA damage in individual cells was exposed under γ-radiation. The increase in the severity of DNA damage was observed with the increase dose (1, 2 and 4Gy) of γ-radiation in cultured hepatocytes. TBARS were increased significantly, whereas the levels of GSH, vitamins C, E and A, ceruloplasmin, uric acid and antioxidant enzymes were significantly decreased in γ-irradiated hepatocytes. The maximum damage to hepatocytes was observed at 4Gy irradiation. On pretreatment with curcumin (1, 5 and 10µg/ml) showed a significant decrease in the levels of TBARS and DNA damage. The antioxidant enzymes were increased significantly along with the levels of GSH, vitamins A, E and C, uric acid and ceruloplamin. The maximum protection of hepatocytes was observed at 10µg/ml of curcumin pretreatment. Thus, pretreatment with curcumin helps in protecting the hepatocytes against γ-radiation-induced cellular damage and can be developed as an effective radioprotector during radiotherapy in near future.

Influence of ferulic acid on gamma-radiation induced DNA damage, lipid peroxidation and antioxidant status in primary culture of isolated rat hepatocytes.

Ionizing radiation is known to induce oxidative stress through generation of reactive oxygen species (ROS) resulting in imbalance of the pro-oxidant and antioxidant activities ultimately resulting in cell death. Ferulic acid (FA) is a phytochemical commonly found in fruits and vegetables such as tomatoes, sweet corn, and ricebran. FA exhibit a wide range of pharmacological effects including antiageing, anti-inflammatory, anticancer, antidiabetic, antiapoptotic, and neuroprotective. The present work is aimed at evaluating the radioprotective effect of FA, on gamma-radiation induced toxicity in primary cultures of isolated rat hepatocytes. Hepatocytes were isolated from the liver of rats by collagenase perfusion. The cellular changes were estimated using lipid peroxidative indices like thiobarbituric acid reactive substances (TBARS), the antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH), ceruloplasmin, Vitamins A, E and C and uric acid. DNA damage was analyzed by single cell gel electrophoresis (comet assay). An increase in the severity of DNA damage was observed with increasing dose (1, 2 and 4Gy) of gamma-radiation in cultured hepatocytes. TBARS were increased significantly, whereas the levels of GSH, Vitamins C, E and A, ceruloplasmin, uric acid and antioxidant enzymes were significantly decreased in gamma-irradiated groups. The maximum damage to hepatocytes was observed at 4Gy irradiation. Pretreatment with FA (1, 5 and 10 microg/ml) significantly decrease the levels of TBARS and DNA damage. In addition, pretreatment with FA significantly increased antioxidant enzymes, GSH, Vitamins A, E and C, uric acid and ceruloplasmin levels. The maximum protection of hepatocytes was observed at 10 microg/ml of FA pretreatment. Thus, pretreatment with FA helps in protecting the hepatocytes against gamma-radiation induced cellular damage and can be developed as a effective radioprotector during radiotherapy.

Fish venom (Pterios volitans) peptide reduces tumor burden and ameliorates oxidative stress in Ehrlich's ascites carcinoma xenografted mice.

The present study was carried out to assess the effect of Pterios volitans venom (mixture of peptides) on Ehrlich's ascites carcinoma (EAC) and its influence on antioxidant status in the liver. Among six groups of albino mice, three were treated with sublethal doses of venom, along with the standard drug, 5-fluorouracil. In EAC-bearing mice, mean life span and antioxidants were significantly decreased, whereas, body weight, tumor volume, viable tumor cell count, lipid peroxidation and expression of proliferating cell nuclear antigen were significantly increased. These changes were brought back to near normal in treatment groups. The findings are further confirmed by histopathological observations.

Effect of spices on lipid metabolism in 1,2-dimethylhydrazine-induced rat colon carcinogenesis.

Colon cancer is the second most common cancer among men and women worldwide. We investigated the effect of red chilli (Capsicum annum L.), cumin (Cuminum cyminum L.), and black pepper (Piper nigrum L.) on colon cancer induced in rats by a colon-specific carcinogen, 1,2-dimethylhydrazine (DMH). Colon cancer was induced by subcutaneous injection of DMH at a dosage of 20 mg/kg of body weight (15 doses, at 1-week intervals). The rats were continued with the standard pellet diet and supplemented red chilli [C. annum L., 0.015% (wt/wt) mixed with the diet], cumin seeds [C. cyminum L., 1.25% (wt/wt) mixed with the diet], and black pepper (P. nigrum L., 0.5% (wt/wt) mixed with the diet] throughout the experimental period. After the total experimental period of 32 weeks (including 2 weeks of acclimatization) the incidence and number of tumors in the colon were observed to be significantly higher in the rats administered DMH and/or red chillis, as compared with the cumin + DMH and black pepper + DMH groups. No tumors were observed in the control, cumin + DMH, or black pepper + DMH groups. The levels of fecal bile acids and neutral sterols in 24-hour fecal samples were significantly decreased in DMH + chilli-administered rats, while the excretion of fecal bile acids and neutral sterols was significantly increased in cumin + DMH- and black pepper + DMH-administered rats. In DMH-, chilli-, and chilli + DMH-administered rats the levels of cholesterol, cholesterol/phospholipid ratio, and 3-hydroxy-3-methylglutaryl-CoA reductase activity were decreased in cumin + DMH- and black pepper + DMH-treated rats. The phospholipid levels were reduced in the DMH, chilli, and chilli + DMH groups as compared with the cumin + DMH and black pepper + DMH groups. Our results show that chilli supplementation promotes colon carcinogenesis, whereas cumin or black pepper suppresses colon carcinogensis in the presence of the procarcinogen DMH.

Protective Role of a Novel Curcuminoid on Alcohol and PUFA-Induced Hyperlipidemia.

Alcohol use is contributing to an unprecedented decline in life expectancy. It induces hyperlipidemia when taken at higher concentrations. Alcoholics usually after a heavy binge of alcohols take fried food items normally made up of polyunsaturated fatty acids (PUFAs). The combined ingestion of alcohol and PUFAs is considered to be dangerous and known to result in hyperlipidemic conditions. Previous studies have shown that curcumin, an active principle of turmeric (Curcuma longa), has antihyperlipidemic properties. So in the present work we have synthesized an analog of curcumin and tested the protective role of that synthetic curcuminoid on alcohol and thermally oxidized sunflower oil-induced hyperlipidemia. Male Albino rats of Wistar strain were used for the experimental study. Antihyperlipidemic activity of the synthetic curcuminoid was evaluated by analyzing the levels of lipids (cholesterol, triglycerides [TGs], phospholipids [PLs], and free fatty acids [FFAs]) in different tissues and histopathological changes in the liver. The results showed that the levels of cholesterol, TGs, and FFAs were increased significantly in alcohol, thermally oxidized sunflower oil (Delta PUFA), and alcohol + Delta PUFAs treated groups. Administration of synthetic curcuminoid effectively reduced these levels. The phospholipid (PL) levels, which were decreased in the liver and kidney and increased in the heart in the alcohol, Delta PUFA, and alcohol + Delta PUFA groups, were positively modulated by treatment with synthetic curcuminoid (CA). Our histopathological observations were also in correlation with the biochemical parameters. From the results obtained, we could conclude that the synthetic curcuminoid effectively protects the system against alcohol and Delta PUFA-induced hyperlipidemia and may become an effective therapeutic agent for the treatment of hyperlipidemia.

Modulatory effects of curcumin on lipid peroxidation and antioxidant status during nicotine-induced toxicity.

Nicotine, a pharmacologically active substance in tobacco, has been identified as a major risk factor for lung diseases. In the present study, we evaluated the protective effects of curcumin on tissue lipid peroxidation and antioxidants in nicotine-treated Wistar rats. Lung toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5 mg/kg (5 days a week, for 22 weeks). Curcumin (80 mg/kg) was given simultaneously by intragastric intubation for 22 weeks. The enhanced level of tissue lipid peroxides in nicotine-treated rats was accompanied by a significant decrease in the levels of ascorbic acid, vitamin E, reduced glutathione, glutathione peroxidase, superoxide dismutase and catalase. Administration of curcumin significantly lowered the level of lipid peroxidation and enhanced the antioxidant status. The results of the present study suggest that curcumin exerts its protective effect against nicotine-induced lung toxicity by modulating the extent of lipid peroxidation and augmenting antioxidant defense system.

Influence of ferulic acid on circulatory prooxidant-antioxidant status during alcohol and PUFA induced toxicity.

In recent years, there has been an escalation in alcohol abuse and inevitably, alcohol related disorders are becoming an increasingly important cause of morbidity and mortality. Alcohol is known to induce a dose dependent increase in lipid peroxidation. Alcohol related disabilities are more pronounced when taken along with diet rich in polyunsaturated fatty acid (PUFA). The present work aims at analysing the protective role of ferulic acid (FA), a naturally occurring nutritional component on alcohol and PUFA induced oxidative stress. Two different doses of ferulic acid, 20 mg/kg body weight and 40 mg /kg body weight were used for the study. The results showed that the levels of oxidative markers; thiobarbituric acid reactive substances (TBARS), hydroperoxides (HP) and levels of copper (Cu) and ferritin were increased significantly in plasma of alcohol, thermally oxidised PUFA (DeltaPUFA) and alcohol + DeltaPUFA groups, which were decreased significantly on treatment with both the doses of ferulic acid. The activities of enzymic antioxidants viz. superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non enzymic antioxidants like vitamin C, vitamin E, and reduced glutathione (GSH) and the levels of zinc (Zn) were significantly decreased in alcohol, DeltaPUFA and alcohol + DeltaPUFA groups which were improved significantly on treatment with both the doses of FA. The reduction in oxidative stress was more significant in 20 mg/kg body weight treatment groups compared to 40 mg/kg body weight. Thus from the results obtained, we conclude that FA effectively protects the system against alcohol and PUFA induced oxidative stress.

Role of an aminothiazole derivative on ethanol- and thermally oxidized sunflower oil-induced toxicity.

It is a known fact that ethanol increases lipid levels in humans and experimental animals. In this study, we have investigated the effect of dendrodoine analogue (DA), DA-[4-amino-5-benzoyl-2-(4-methoxyphenylamino)-thiazole], on alcohol- and thermally oxidized sunflower oil-induced hyperlipidemia. Ethanol was given to animals at a dose of 5 ml of 20% solution and thermally oxidized sunflower oil at a level of 15% (15 g oil/100 g feed). Our results showed increased activity of aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) and increased levels of cholesterol, triglycerides and phospholipids in the plasma of groups given alcohol, thermally oxidized oil and alcohol + thermally oxidized oil when compared with normal control group. The levels of tissue (liver and kidney) cholesterol and triglycerides were increased significantly in groups treated with alcohol, thermally oxidized oil and alcohol + thermally oxidized oil when compared with normal control rats. The levels were decreased when DA was given along with alcohol and thermally oxidized oil. The level of phospholipids decreased significantly in the liver and kidney of rats administered alcohol, thermally oxidized oil and alcohol + thermally oxidized oil when compared with normal control rats. The level increased when DA was administered along with alcohol and thermally oxidized oil. The activity of phospholipase A and C increased significantly in the liver of groups given alcohol, thermally oxidized oil and alcohol + thermally oxidized oil when compared with normal control rats, whereas the activity was decreased upon DA treatment. The obtained results indicate that DA can decrease the lipid levels in alcohol- and thermally oxidized oil-treated rats.

Protective effects of ferulic acid on hyperlipidemic diabetic rats.

Diabetes, when uncontrolled, causes dyslipidemia often followed by atherogenic abnormalities. The present study was focused to determine whether ferulic acid (FA), a flavonoid, has any role to play in diabetes-induced dyslipidemia. Diabetes in rats was induced with streptozotocin. The levels of blood glucose and plasma triglycerides (TG), free fatty acids (FFA), cholesterol and phospholipids were elevated during diabetes. Treatment with FA significantly reduced the elevated plasma lipid and blood glucose levels; a more pronounced effect was found with low-dose ferulic acid than with high dose. Thus, our study demonstrates that ferulic acid lowers the lipid levels in diabetic rats and hence prevents further complications.