Antigenotoxic Effect of Ferulic Acid in 7;12-Dimethyl Beza (A) - Anthracene (DMBA) Induced Genotoxicity

The antigenotoxic effect of ferulic acid was carried out by evaluating the cytogenetic markers; the micronuclei frequency and chromosomal aberrations; in the bone marrow of hamsters in 7;12dimethylbenz(a)anthracene (DMBA) induced genotoxicity. Genotoxicity was induced in experimental hamsters by single intraperitoneal injection of DMBA (30mg kg-1 b.w). Pretreatment of ferulic acid orally at a dose of 40mg kg-1 b.w for five days significantly reduced the frequency of micronucleated polychromatic erythrocytes (MnPCEs) and the percentage of chromosomal aberrations in hamster's bone marrow. Our results thus suggest that ferulic acid has potent antigenotoxic effect in DMBA induced genotoxicity in golden Syrian hamsters

Histopathological and lipid changes in experimental colon cancer: effect of coconut kernal (Cocos nucifera Linn.) and (Capsicum annum Linn.) red chilli powder.

Influence of coconut kernal and red chilli on the metabolism of lipids was studied in animals given 1,2-dimethylhydrazine (DMH). The average weight gain by the animals in the coconut kernal group was more than DMH and chilli treated groups. The concentration of cholesterol showed a decrease and phospholipids an increase in most of the tissues studied, of the kernal groups. The cholesterol-phospholipid ratio was found to be increased in most of the tissues of all experimental groups, when compared to control animals. HMG CoA reductase activity decreased in the high fat and most of the tissues of the kernal + DMH, kernal + chilli and kernal + chilli + DMH groups, while it increased in the DMH, chilli and chilli + DMH groups. Histopathological studies showed that coconut kernal supplemented animals had fewer papillae, lesser infiltration into the submucosa and lesser changes in the cytoplasm with decreased mitotic figures. Coconut kernal, thus reduced the mutagenic and carcinogenic effect of chilli and DMH respectively.

Role of redchilli (Capsaicin) in the formation of colonic carcinoma.

The effect of feeding redchilli (Capsaicin) powder on the histopathological changes occurring in the colonic mucosa was studied in rats. These animals were compared with those treated with a colonic carcinogen 1,2-dimethylhydrazine (DMH). Animals fed with redchilli, dimethylhydrazine, dimethylhydrazine plus redchilli powder showed polyp and dysplasia, malignant tumour and malignant tumour with transitional area of dysplasia.

Protective effect of testosterone against alcohol and paracetamol induced hepatotoxicity in rats.

Chronic ethanol and paracetamol consumption, both individually and in combination, caused hepatic changes in rats. Treatment of testosterone (2.5 mg/kg body wt.) to the alcoholic and paracetamol administered rats showed decreased activities of serum transaminases, serum acid and alkaline phosphatases, and decreased levels of hepatic triglycerides, cholesterol and free fatty acids. Concentration of the lipid peroxidation product-malondialdehyde was significantly decreased in the liver after testosterone treatment in alcohol and paracetamol administered groups. Histopathological observations further confirm that testosterone could offer protection against alcohol and paracetamol induced damage to liver in animals.

Influence of red chilli on lipids and bile acids in different tissues in experimental colon cancer.

Effect of feeding red chilli on the levels of lipids, fecal bile acids and fecal sterols was studied in animals given 1,2-dimethylhydrazine (DMH). When the three experimental groups were compared with control, the levels of cholesterol increased while phospholipids and free fatty acids decreased or showed no alteration in most of the tissues studied. Cholesterol-phospholipid ratio was high in both DMH as well as in the chilli + DMH treated groups. Weekly assessment of bile acids and neutral sterols showed a significant increase in all the three experimental groups, when compared to the control rats. Morphological and histopathological studies show that there were a number of visible malignant tumors in the colon and intestine of all the three experimental animals.

Long term administration of testosterone on ascorbic acid metabolism in castrated rats.

Orchidectomy caused a significant decrease in the concentration of ascorbic acid and ascorbic acid-2-sulphate in tissues while administration of testosterone to these animals reverses this effect. Concentration of ascorbic acid in liver in experimental groups correlates with the activity of L-qualano-lactone oxidase and dehydroascorbatase in this tissue.

Lipid peroxide metabolism in oophorectomised rats.

The effect of bilateral oophorectomy and the administration of beta-estradiol on lipid peroxide metabolism were studied in rats. The lipid peroxide levels were measured in the oophorectomised and the estradiol administered animals. The level of lipid peroxide increased in the liver in oophorectomised animals, whereas no change was observed in the heart. The activity of antiperoxidative enzymes superoxide dismutase and catalase was found to be decreased in both the liver and the heart. Oophorectomy resulted in the elevation of serum ceruloplasmin. Administration of estradiol to oophorectomised rats restored the altered lipid peroxide levels.

Role of lipid peroxides, glutathione and antiperoxidative enzymes in alcohol and drug toxicity.

Ethanol administration to rats for 30 days and 90 days followed by paracetamol administration resulted in liver injury indicated by the significant increase in the serum GOT and GPT levels. The ethanol treatment to rats and the administration of paracetamol to the normal and alcoholic rats also caused a significant increase in the activity of serum acid and alkaline phosphatase. The hepatotoxicity of ethanol and paracetamol were indicated by the histological alterations in this study. The content of lipid peroxidation products-malondialdehyde, hydroperoxides and conjugated dienes were increased in the liver, heart, kidney and brain of the acute and chronic ethanol treated and paracetamol treated rats. The activities of the antiperoxidative enzymes-SOD and catalase decreased in the ethanol and paracetamol treated rats. The changes in the activities of the antiperoxidative enzymes in alcoholism and drug toxicity suggests increased peroxidation, increased synthesis of ecosonoids and increased damage to the tissues. The glutathione levels were decreased in the rats administered ethanol for 30 days, while the glutathione levels increased in the 90 days ethanol treated rats. The paracetamol treatment caused a decrease in the glutathione levels in the normals and the ethanol treated rats.

Testosterone and lipid peroxide metabolism in orchidectomised rats.

The effect of testosterone on lipid peroxides and antiperoxidative enzymes in normal and orchidectomised animals has been studied. Orchidectomy results in increased lipid peroxidation in the heart, while administration of testosterone to the animals reverses this to a certain extent. On the other hand the administration of testosterone to normal rats results in increased lipid peroxidation in the liver and heart.

Role of antibiotics in lipid peroxidation.

Alterations in the levels of lipid peroxides, superoxide dismutase, catalase, glutathione, free fatty acid and serum ceruloplasmin were studied in rats fed with high fat cholesterol diet administered different antibiotics, viz. ampicillin, tetracycline, streptomycin, chloramphenicol and cephalosporin. The concentrations of lipid peroxides, glutathione, free fatty acid decreased in most of the tissues, except in tetracycline, streptomycin and cephalosporin treated rats. The changes observed in the activities of superoxide dismutase and catalase in the liver and kidney of these antibiotics administered groups also are in accordance with the changes in lipid peroxides. The results show that the tetracycline is hepatotoxic and nephrotoxic, while cephalosporin and streptomycin are nephrotoxic.

Peroxidative changes in experimental diabetes mellitus.

Changes in the levels of lipid peroxides and antioxidant enzymes were studied in male albino rats with experimental diabetes mellitus. Diabetes was induced by single subcutaneous injection of alloxan (19 mg/100 g body weight). The concentration of malondialdehyde (MDA) showed an increase both in the liver (P less than 0.01) and kidney (0 less than 0.05), while in the heart, there was a decrease (P less than 0.01), as compared to control values. A similar pattern of change was observed in the level of hydroperoxides in the liver and heart. The conjugated dienes showed an elevation during diabetes in all tissues (P less than 0.01). Glutathione levels in heart (P less than 0.01) and kidney were found to be decreased (P less than 0.05) while the liver showed an elevation during long-term diabetes (P less than 0.01). Serum ceruloplasmin showed an increase (P less than 0.05) in diabetes. Antioxidant enzymes superoxide dismutase and catalase decreased in all tissues (P less than 0.01) while the activity of glutathione s-transferase increased in heart, but no change in other tissues. The studies thus show that lipid peroxidation is activated in liver and kidney while heart tissues show some resistance towards lipid peroxidation.

Changes in levels of lipid peroxides and activity of superoxide dismutase and catalase in diabetes associated with myocardial infarction.

Studies were carried out on the metabolism of lipid peroxides and antioxidative enzymes during diabetes and diabetes superimposed with myocardial infarction. Diabetes was induced using alloxan and myocardial infarction was induced by isoproterenol. In the case of diabetic animals there was a decrease in the levels of lipid peroxides in the heart while in the case of diabetes associated with myocardial infarction it was slightly elevated. The activity of superoxide dismutase and catalase showed a decrease in both the groups. Glutathione showed a fall in the case of diabetes and diabetes associated with myocardial infarction while taurine in heart and ceruloplasmin in the serum was elevated. Histopathological changes in the heart tissue showed some focal changes in the case of both diabetes and diabetes associated with myocardial infarction, but the degree of necrosis was much less than in the case of myocardial infarction.

Dietary fiber and lipid peroxidation: effect of dietary fiber on levels of lipids and lipid peroxides in high fat diet.

Effect of feeding coconut and blackgram fiber isolated as neutral detergent fiber (NDF) on the levels of lipids and lipid peroxides was studied in rats given a high fat diet. Concentration of cholesterol, free falty acid and phospholipids showed significant decrease in the serum, liver aorta and intestine of coconut and blackgram fiber groups. Concentration of malondialdehyde (MDA) and conjugated dienes was significantly decreased in liver and intestine of both fiber groups, while hydroperoxides showed significant increase in liver and heart of both the fiber groups. SOD and catalase activity was found to be increased in liver, intestine, heart proximal colon and distal colon of both the fiber groups. Serum ceruloplasmin levels showed a slight increase in animals fed coconut and blackgram fiber groups. Glutathione levels in liver, intestine proximal colon, distal colon and heart also showed a significant decrease in the animals of both the fiber groups.

Protective action of aspirin in experimental myocardial infarction induced by isoproterenol in rats and its effect on lipid peroxidation.

The protective action of aspirin in experimental myocardial infraction induced by isoproterenol was studied in rats. Aspirin treated rats showed lower mortality rate and smaller changes in the myocardium on histopathological examination when compared to corresponding animals given isoproterenol alone. Changes were also observed in the different lipid fractions studied. The ratio of cholesterol to phospholipids decreased in the heart in aspirin treated animals when compared to control rats given isoproterenol alone. The levels of lipid peroxide also showed a decrease while the activity of superoxide dismutase (SOD) and catalase registered an increase in the aspirin treated animals given isoproterenol when compared to corresponding animals given isoproterenol alone.

Effect of vitamin E on the severity of myocardial infarction induced by isoproterenol.

The effect of vitamin E administration on the severity of myocardial infarction induced by isoproterenol on rats was studied. Judging from serum enzyme activity (CPK 714 micromoles; GOT 291.7 micromoles; and GPT 155.5 micromoles), mortality rate (60 to 65% survived) and histopathological observation, vitamin E has been observed to offer very little protection to the myocardium during experimental myocardial infarction when compared to control animals given isoproterenol alone (CPK 775.8 micromoles; GOT 336.2 micromoles; and GPT 168 micromoles), mortality rate (60 to 65% survived) and histopathological observation (more or less similar). The level of lipid peroxides namely hydroperoxides (control 3.15; vitamin E + iso. 14.8); conjugated diene (4.45 and 6.85) and malondialdehyde (1.22 and 2.55) in the heart were higher in the vitamin E treated animals given isoproterenol when compared to control animals given vitamin E alone. The level of cholesterol and phospholipid was more or less similar in the control animals given vitamin E alone (183.6 and 3.12) and vitamin E treated animals given isoproterenol (170.25 and 2.49), but the ratio of cholesterol to phospholipid was higher in the vitamin E treated animals given isoproterenol when compared to control animals given vitamin E alone.

Effect of carnitine on malondialdehyde, taurine and glutathione levels in heart of rats subjected to myocardial stress by isoproterenol.

The effect of carnitine on free fatty acid, malondialdehyde, taurine and glutathione levels in myocardium was studied in rats administered isoproterenol to induce a stress in the myocardium resulting in myocardial ischaemia. Carnitine decreased the levels of free fatty acid and malondialdehyde (an index of lipid peroxidation) when compared to control rats given isoproterenol alone. Taurine and glutathione also registered a fall in the carnitine treated animals when compared to rats treated with isoproterenol alone. The results indicate that carnitine by decreasing the levels of these parameters helps the myocardium to survive from the stress induced by isoproterenol.