Garlic oil ameliorates ferric nitrilotriacetate (Fe-NTA)-induced damage and tumor promotion: implications for cancer prevention.

Intraperitoneal injection of ferric nitrilotriacetate (Fe-NTA) to rats and mice results in iron-induced free radical injury and cancer in kidneys. This study was designed to investigate the effects of garlic oil on Fe-NTA-induced damage and tumor promotion. Pretreatment of rats with garlic oil at a dose regimen of 50-100 mg/kg body weight for a week significantly and dose dependently protected against Fe-NTA induced damage as well as tumor promotion. Garlic oil afforded protection against hepatic lipid peroxidation, generation of hydrogen peroxide, preserved glutathione levels and activities of antioxidant enzymes. A protection against Fe-NTA induced hepatic tumor promotion was also apparent as inhibition in the modulation of hepatic tumor markers viz., ornithine decarboxylase activity and DNA synthesis. These results clearly demonstrate the role of oxidative stress and its relation to tumor promotion and suggest protective effects of garlic oil against Fe-NTA induced hepatic toxicity and it can serve as potent chemopreventive agent to suppress oxidant-induced tissue injury and carcinogenesis.

Purification and characterization of an extracellular protease produced by psychrotolerant Clostridium sp. LP3 from lake sediment of Leh, India.

An anaerobic, proteolytic bacterium isolated from lake sediments of Leh, India, was characterized with respect to morphology, biochemical characteristics, and 16S rRNA sequence and was identified as Clostridium species, with closest similarity to Clostridium subterminale. Isolate LP3 was psychrophilic, forming maximum cell mass between 10 and 20 degrees C, and produced extracellular protease. Growth was observed in the pH range of 7.0-8.5, with optimum at pH 7.5. Protease was purified 62.4-fold with a total yield of 17.5%. The effects of temperature, pH, and salt concentration on enzyme activity were studied. Protease was found to be a serine-type metallo-enzyme, active in a broad range of pHs. It was thermolabile and resistant to sodium dodecyl sulfate. Enzyme kinetics showed a tendency to increase Km with an increase in temperature for casein substrate.

Inhibitory effect of 18beta-glycyrrhetinic acid on 12-O-tetradecanoyl phorbol-13-acetate-induced cutaneous oxidative stress and tumor promotion in mice.

Glycyrrhetinic acid is an aglycone of glycyrrhizic acid, another major active component of licorice roots. Licorice root extract has been used for a long time as a medicine and a natural sweetening additive. In the present study, we found that glycyrrhetinic acid inhibits 12-O-tetradecanoylphorbol-13-acetate (TPA) mediated oxidative stress and tumor promotion in murine skin. Topical application of TPA alone in mouse skin enhances ornithine decarboxylase activity and also increases [3H]-thymidine incorporation in DNA. Topical application of TPA also resulted in the depletion of glutathione, activities of glutathione metabolizing and antioxidant enzymes. Application of glycyrrhetinic acid prior to TPA treatment reduces this enhanced ODC activity, [3H]-thymidine incorporation in DNA and oxidative stress. Glycyrrhetinic acid was also found to inhibit DMBA/TPA-induced skin tumor formation at doses of 1.25 and 2.5 mg by reducing the number of tumors per mouse by 24% (P < 0.05) and 62% (P < 0.05), respectively. These results suggest that glycyrrhetinic acid, an antioxidant, is a potential chemopreventive agent that can inhibit DMBA/TPA-induced cutaneous oxidative stress and tumor promotion.

Vitamin E inhibits hepatic oxidative stress, toxicity and hyperproliferation in rats treated with the renal carcinogen ferric nitrilotriacetate.

Ferric nitrilotriacetate (Fe-NTA) is a potent renal and hepatic tumor promoter, which acts through a mechanism involving oxidative stress. Fe-NTA when injected intraperitoneally into rats induces hepatic ornithine decarboxylase activity as well as hepatic DNA synthesis. Vitamin E is a well-known, lipid-soluble and chain-breaking antioxidant which protects cell membranes from peroxidative damage. In this study, we investigated the protective effect of vitamin E, a major fat-soluble antioxidant, against Fe-NTA-mediated hepatic oxidative stress, toxicity and hyperproliferation in Wistar rats. Animals were treated with two different doses of vitamin E for 1 week prior to Fe-NTA treatment. Vitamin E at a higher dose of 2.0 mg/animal/day showed significant reduction in Fe-NTA-induced hepatic ornithine decarboxylase activity, DNA synthesis, microsomal lipid peroxidation and hydrogen peroxide generation. Fe-NTA treatment alone caused depletion of glutathione, glutathione metabolizing and antioxidant enzymes in rat liver, whereas pretreatment of animals with vitamin E reversed these changes in a dose-dependent manner. Taken together, our results suggest that vitamin E may afford substantial protection against the damage caused by Fe-NTA exposure and can serve as a potent preventive agent to suppress oxidant-induced tissue injury.