Namasivayam Nalini

What Is New for an Old Molecule? Systematic Review and Recommendations on the Use of Resveratrol

Background Resveratrol is a natural compound suggested to have beneficial health effects. However, people are consuming resveratrol for this reason without having the adequate scientific evidence for its effects in humans. Therefore, scientific valid recommendations concerning the human intake of resveratrol based on available published scientific data are necessary. Such recommendations were formulated after the Resveratrol 2010 conference, held in September 2010 in Helsingør, Denmark. Methodology Literature search in databases as PubMed and ISI Web of Science in combination with manual search was used to answer the following five questions: 1Can resveratrol be recommended in the prevention or treatment of human diseases?; 2Are there observed “side effects” caused by the intake of resveratrol in humans?; 3What is the relevant dose of resveratrol?; 4What valid data are available regarding an effect in various species of experimental animals?; 5Which relevant (overall) mechanisms of action of resveratrol have been documented? Conclusions/Significance The overall conclusion is that the published evidence is not sufficiently strong to justify a recommendation for the administration of resveratrol to humans, beyond the dose which can be obtained from dietary sources. On the other hand, animal data are promising in prevention of various cancer types, coronary heart diseases and diabetes which strongly indicate the need for human clinical trials. Finally, we suggest directions for future research in resveratrol regarding its mechanism of action and its safety and toxicology in human subjects.

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

Abstract 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.

Dietary supplementation of resveratrol suppresses colonic tumour incidence in 1,2-dimethylhydrazine-treated rats by modulating biotransforming enzymes and aberrant crypt foci development

Diet-induced changes in the activities of bacterial enzymes are known to play a role in colon cancer development. Resveratrol has been implicated as a protective agent in carcinogenesis. In the present study, the effect of resveratrol on the activities of faecal and colonic biotransforming enzymes such as beta-glucuronidase, beta-glucosidase, beta-galactosidase, mucinase, nitroreductase and faecal sulfatase activity was assessed. The total number of aberrant crypt foci and their distribution in the proximal, medial and distal colon were observed in 1,2-dimethylhydrazine (DMH)-induced rats (group 3) and other treatment groups (groups 4-6). DMH (0.02 g/kg body weight) was given subcutaneously once a week for 15 consecutive weeks, and the experiment was terminated at 30 weeks. DMH-treated rats showed elevated levels of cancer-associated bacterial enzyme activities, whereas on resveratrol supplementation in three different regimens, rats showed lowered activities. Resveratrol supplementation throughout the experimental period (group 6) exerted a more pronounced effect (P < 0.01) by modulating the development of aberrant crypt foci and the activities of bacterial enzymes than did the other treatment regimens (groups 4 and 5). Thus, the present results demonstrate the inhibitory effect of resveratrol on DMH-induced colon carcinogenesis in rats.

Role of leptin on alcohol-induced oxidative stress in Swiss mice

Previous studies suggest a possible link between leptin and hepatic inflammation; however, the role of leptin on liver disease remains unclear. The purpose of the present study was to evaluate the effect of leptin on tissue lipid peroxidation and the antioxidant status in experimental hepatotoxicity. Administering ethanol (6.32 g/kg body weight) to 4-week-old healthy mice for 45 days resulted in significantly elevated levels of tissue thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and lowered activities of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and glutathione related enzymes such as glutathione peroxidase (GPx) and glutathione S-transferase (GST) as compared with those of the control mice. subsequent to the experimental induction of hepatotoxicity (i.e. after the initial period of 30 days) exogenous leptin was simultaneously administered (230 microg/kg body weight) every alternate day for 15 days along with the daily dose of alcohol. Leptin administration to control and alcohol-treated mice significantly reduced the weight gain, significantly elevated the liver and kidney levels of TBARS and CD, and significantly lowered the levels of enzymic and non-enzymic antioxidants as compared with the untreated control and alcohol supplemented mice. It is postulated that the increase in systemic leptin levels enhance the oxidative stress, and lower the antioxidant defence, leading to augmented hepatic inflammation in alcoholic liver disease.

Circulating lipid peroxidation and antioxidant status in cervical cancer patients: a case-control study

OBJECTIVES The present case-control study was conducted to investigate the status of circulating lipid peroxidation and the enzymic and nonenzymic antioxidants of cervical cancer patients. DESIGN AND METHODS Plasma thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and the levels of antioxidants such as reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), vitamin C and vitamin E were estimated in circulation of thirty patients and an equal number of age matched normal subjects as control. RESULTS Significantly elevated levels of plasma TBARS and CD and significantly lowered levels of GSH, GPx, GST, SOD vitamin C and vitamin E were observed in cervical cancer patients as compared to controls. Our study reveals increased lipid peroxidation and possible breakdown of antioxidant status in patients with cervical carcinoma. CONCLUSION These results indicate that low levels of GSH, GPx, GST, SOD, vitamin E and vitamin C in the circulation of cervical cancer patients may be due to their increased utilization to scavenge lipid peroxides as well as their sequestration by tumor cells. Malnutrition may also be a significant cause for the increased prevalence of cervical cancer in women with a low socioeconomic status.

Influence of spices on the bacterial (enzyme) activity in experimental colon cancer.

In the presence of a known colon carcinogen, 1,2-dimethyl hydrazine (DMH), the activity of beta-glucuronidase was found to be significantly increased in the distal colon, distal intestine, liver and colon contents and the activity of mucinase was increased in both the colon and fecal contents when compared to control rats. Chilli (Capsicum annum L., Solanaceae) administration also showed an increase when compared to control rats, whereas supplementation with cumin (Cuminum cyminum L., Apiaceae) and black pepper (Piper nigrum L., Piperaceae) in the presence of DMH, showed more or less similar values as that of the control rats. The increase in beta-glucuronidase activity may increase the hydrolysis of glucuronide conjugates, liberating the toxins, while the increase in mucinase activity may enhance the hydrolysis of the protective mucins in the colon. Thus cumin and black pepper may protect the colon by decreasing the activity of beta-glucuronidase and mucinase. Histopathological studies also showed lesser infiltration into the submucosa, fewer papillae and lesser changes in the cytoplasm of the cells in the colon in cumin and black pepper groups when compared to the DMH and chilli treated animals.

Efficacy of the potential chemopreventive agent, hesperetin (citrus flavanone), on 1,2-dimethylhydrazine induced colon carcinogenesis

Our current study is an effort to identify a potent chemopreventive agent against colon cancer. Here we have investigated the efficacy of hesperetin on tissue lipid peroxidation, antioxidant defense system and colonic histoarchitecture in male Wistar rats in colon carcinogenesis. Rats in groups 3, 4, 5 and 6 were treated with DMH (20 mg kg body weight s.c.) once a week for 15 weeks. Group 1 rats received modified pellet diet and served as control; group 2 received modified pellet diet along with hesperetin (20mg/kg body weight, p.o., every day); and hesperetin was given to the rats as in-group 2 during the initiation, post-initiation and entire period stages of colon carcinogenesis. Lipid peroxidation was studied by measuring the formation of thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH) and conjugated dienes (CD), and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), reduced glutathione (GSH), in the liver and colonic tissues of DMH administered rats. (1) Decreased levels of lipid peroxidation in the colonic tissues; (2) decreased activities of antioxidant enzymes SOD, CAT, GPX, GR and GSH levels in the tissues on DMH treatment. Hesperetin supplementation during the initiation, post-initiation and entire period stages of carcinogenesis significantly reversed these activities. These results indicate that hesperetin may be a potential chemopreventive agent against DMH-induced colon cancer.

Resveratrol ameliorates DNA damage, prooxidant and antioxidant imbalance in 1,2-dimethylhydrazine induced rat colon carcinogenesis.

Colorectal cancer is one of the most common internal malignancies in Western society. Currently oxidative stress has been increasingly postulated as a major contributor to carcinogenesis. The assessment of damage in various biological matrices, such as tissues and cells, is vital to understand the development of carcinogenesis and subsequently devising intervention strategies. Thus, the major objective of the present study was to examine the effect of resveratrol (Res) on DNA damage in a short-term study of 16 days and circulatory lipid peroxidation, enzymic/non-enzymic antioxidants status in a long-term study of 30 weeks in 1,2-dimethylhydrazine (DMH) induced colon carcinogenesis. Wistar male rats were divided into 6 groups, group 1 were control rats, group 2 rats received Res (8mg/kg body weight, orally, everyday), rats in groups 3-6 were administered (DMH, 20mg/kg body weight, s.c.) as four injections in order to induce DNA damage in the short-term or once a week for the first 15 weeks in the long-term study. In addition to DMH, group 4 (initiation), 5 (post-initiation) and 6 (entire-period) received Res (8mg/kg body weight, p.o., everyday). The results revealed that, supplementation with Res (entire-period) treatment regimen significantly reduced the DMH-induced leukocytic DNA damage (tail length, tail moment, % DNA in the comet tail and olive tail moment) as compared to DMH-alone treated rats. In addition, entire-period Res supplementation increased the enzymic (superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and glutathione S-transferase) and non-enzymic (reduced glutathione, vitamin C, vitamin E and beta-carotene) antioxidant status with a corresponding decrease in the extent of lipid peroxidation markers (thiobarbituric acid reactive substances, diene conjugates and lipid hydroperoxides). Conversely, Res supplementation during initiation and post-initiation regimen did not produce greater modulatory effects. Our results indicate that DMH-induced DNA damage and oxidative stress were suppressed/prevented effectively by chronic Res supplementation.

Piperine, an Active Principle from Piper Nigrum, Modulates Hormonal and Apolipoprotein Profiles in Hyperlipidemic Rats

PURPOSE To study the effect of piperine, an alkaloid, on thyroid hormones and apolipoproteins in high-fat-diet (HFD) and antithyroid drug-induced hyperlipidemic rats. EXPERIMENTAL Male Wistar rats were first divided into two groups, control diet and high-fat diet (HFD) and then subdivided into four subgroups of ten animals each. The animals were treated with the following regimens for 10 weeks: 1% carboxymethyl cellulose; 10 mg carbimazole (CM)/kg body weight; 10 mg CM + 40 mg piperine/kg body weight, and 10 mg CM + 2 mg atorvastatin /ATV//kg body weight. Lipid profiles, hormone levels, and apolipoprotein levels were studied in all groups. RESULTS HFD and/or CM administration significantly elevated the plasma levels of total cholesterol, VLDL, LDL, triglycerides, free fatty acids, and phospholipids, but significantly reduced the HDL levels. Moreover, CM administration significantly reduced apo A-I levels and T3, T4 and testosterone levels while significantly elevating plasma apo B, thyroid stimulating hormone (TSH) and insulin levels. The simultaneous administration of piperine and HFD significantly reduced plasma lipids and lipoproteins levels, except for HDL, which was significantly elevated. Piperine supplementation also improved the plasma levels of apo A-I, T3, T4, testosterone, and I and significantly reduced apo B, TSH, and insulin to near normal levels. CONCLUSIONS The data presented here provide evidence that piperine possesses thyrogenic activity, thus modulating apolipoprotein levels and insulin resistance in HFD-fed rats, opening a new view in the management of dyslipidemia by dietary supplementation with nutrients.

Effect of hesperetin, a citrus flavonoid, on bacterial enzymes and carcinogen-induced aberrant crypt foci in colon cancer rats: a dose-dependent study.

Hesperetin, an important bioactive compound in Chinese traditional medicine, has antioxidant and anticarcinogenic properties. Hesperetin is found in abundance in orange and grape juices (200–590 mg L−1) consumed in the daily diet. We have investigated the effect of different doses of hesperetin on faecal and colonic mucosal bacterial enzymes and aberrant crypt foci (ACF) in 1,2‐dimethylhydrazine (DMH)‐induced colon carcinogenesis in male Wistar rats. The rats were divided into six groups and were fed a modified pellet diet for 16 weeks. Group 1 served as control and group 2 received the modified pellet diet along with hesperetin (30 mg kg−1). The rats in groups 3–6 rats were given a weekly subcutaneous injection of DMH (20 mg kg−1) for the first four weeks. Hesperetin was supplemented orally at different doses (10, 20 or 30 mg kg−1) for a total of 16 weeks. At the end of the experimental period all rats were killed. In DMH‐treated rats, the activity of faecal and colonic mucosal bacterial enzymes, such as β‐glucuronidase, β‐galactosidase, β‐glucosidase, nitroreductase, sulfatase and mucinase, were significantly elevated, but in rats supplemented hesperetin along with DMH the activity was significantly lowered (P < 0.05). The total number of aberrant crypts was significantly increased in unsupplemented DMH‐treated rats, while hesperetin supplementation to DMH‐treated rats significantly reduced the total number of crypts. The results demonstrated that hesperetin supplementation at a dose of 20 mg kg−1 played a potent role in suppressing the formation of aberrant crypt foci and reducing the activity of bacterial enzymes in colon cancer.