methylnitronitrosoguanidine and allyl-sulfide

Stavudine (Zerit, d4T) is widely used as an anti HIV infection drug. It prevents HIV by altering the genetic material of healthy cells but causes mutations in mitochondrial and nuclear DNA. It also produces clastogenic effects in mice. In the present investigation, comet assay test was applied to evaluate the possible genomic damage caused by stavudine and also the ameliorating effects of garlic oil and vitamin E against its genotoxicity in different organs of mice. Two different doses of garlic oil (low and high dose) and vitamin E were administered to mice separately and in combination for six consecutive days followed by a dose of stavudine. The mice were sacrificed after 24, 48 and 72 h of stavudine administration. Both the antioxidants (vitamin E and garlic oil) separately and in combination reduced the genotoxicity of stavudine. The protective effects of high doses of garlic oil were more pronounced as compared to vitamin E administered group.

Topics: Allyl Compounds; Animals; Anti-HIV Agents; Comet Assay; DNA Damage; Male; Methylnitronitrosoguanidine; Mice; Mutagens; Organ Specificity; Stavudine; Sulfides; Vitamin E

In order to predict the chemopreventive activity of garlic on gastric cancer, the effect of diallyl sulfide (DAS), a natural extract of the garlic, on MNNG-induced nuclear aberration (NA) and ornithine decarboxylase (ODC) activity in Wistar rat glandular stomach mucosa was studied. The results showed that NA and ODC activity were positively correlated to MNNG dose given 24 and 6 hr after oral intubation with MNNG. Oral or parenteral pretreatment with DAS significantly and dose-dependently inhibited MNNG-induced NA and ODC. These data suggest that DAS has the potential to inhibit MNNG-induced gastric cancer, supporting the epidemiological evidence of the chemopreventive effect of garlic on gastric cancer.

Topics: Allyl Compounds; Animals; Cell Nucleus; Dose-Response Relationship, Drug; Garlic; Gastric Mucosa; Male; Methylnitronitrosoguanidine; Ornithine Decarboxylase; Plants, Medicinal; Rats; Rats, Inbred Strains; Stomach Neoplasms; Sulfides

In previous investigations using models for gastrointestinal cancer, the anticarcinogenic effects of diallyl sulfide (DAS), an organosulfur compound present in garlic, was established. In this study, we conducted experiments to determine whether DAS modulates two biomarkers, nuclear aberrations (NA) and ornithine decarboxylase (ODC) activity, in the glandular stomach mucosa of the Wistar rat. N-methyl-N'-nitro-N-nitrosoguanidine (MN-NG) induced dose-related NA and ODC activity in the glandular stomach 24 h and 6 h, respectively, after oral intubation with the carcinogen. Either oral or parenteral pretreatment with DAS significantly reduced the MNNG induction of NA or ODC. Furthermore, the suppressions were observed to be dose dependent. These data suggest that DAS may potentially inhibit MNNG-induced gastric cancer. In view of recent epidemiologic evidence linking reduced risk for gastric cancer with increased consumption of allium vegetables, it is clear that DAS has pluripotent effects as an anticarcinogen, although studies addressing a mechanism of action have yet to be reported.

Topics: Allyl Compounds; Animals; Cell Nucleus; Dose-Response Relationship, Drug; Gastric Acidity Determination; Gastric Mucosa; Male; Methylnitronitrosoguanidine; Ornithine Decarboxylase; Rats; Rats, Inbred Strains; Sulfides