Skin tumorigenic potential of aflatoxin B1 in mice.

Aflatoxin B1 (AFB1) has been classified as a category I human carcinogen, which is responsible for a high incidence of hepatocellular carcinoma. Since exposure to AFB1 can occur through skin contact in addition to ingestion and inhalation, the carcinogenic potential of topically applied AFB1 on mouse skin was investigated. Our results show that single topical application of AFB1 (80 nmol) as a tumor initiator, followed by twice weekly application of 12-tetradecanoyl phorbol myristate acetate (TPA, 4 nmol), resulted in tumor formation after 13 weeks. However, no tumorigenic potential was observed when AFB1 (16 nmol) was used either as a complete carcinogen or as a tumor promoter (4 nmol). Histological analysis of skin showed squamous cell carcinoma in the AFB1/TPA treated group. The application of AFB1 as a complete carcinogen, an initiator or a promoter after 24 weeks demonstrated widespread degenerative and necrotic changes in hepatic tissue as well, suggesting liver to be the target organ following percutaneous absorption. Additionally, twice weekly topical application of AFB1 caused significant induction of cutaneous CYP IA monoxygenases without any effect on hepatic levels while glutathione-S-transferase activity was induced more in the liver than skin. The topical application of AFB1 also resulted in increased hepatic and cutaneous lipid peroxidation with concomitant depletion of glutathione content. It is likely that due to higher induction of hepatic GST activity, products of lipid peroxidation may be detoxified and therefore unable to cause DNA damage making mice resistant to hepatic tumor formation. The overall results indicate a tumor initiating potential of AFB1 in mice and suggest that continued dermal exposure of AFB1, even at low doses, might lead to degenerative changes in hepatocytes.

Prevention of acute cadmium toxicity by Picroliv.

The potential of Picroliv, a herbal extract against acute cadmium (Cd) intoxication, was evaluated in male rats. Biochemical and histopathological profile in rats pretreated with Picroliv (12 mg/kg, oral) followed by a single dose of Cd as cadmium chloride (CdCl2) (3 mg/kg, ip) revealed marked suppression of oxidative stress in liver and testes. The Cd-induced enhanced levels of lipid peroxidation, membrane fluidity and reduced levels of nonprotein sulphydryls and Na(+)K(+)ATPase were significantly restored to near normal by Picroliv pretreatment. In addition, the Cd-induced serum levels of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, gamma glutamyl transpeptidase and lactate dehydrogenase were restored to near basal levels. Hepatic and testicular histopathological damage was also minimized. The results strongly suggest definite hepato- and testicular protection by Picroliv. The antioxidant potential of the herbal extract in the major part, and not its chelating property, seems to be responsible for its ameliorative action.

Exacerbation of soft tissue lesions in lead exposed virus infected mice.

OBJECTIVE: To investigate the effect of Lead (Pb) acetate exposure on Semliki forest virus (SFV) pathogenesis in mice. METHODS: Different doses (62.5, 125, 250 and 500 mg/Kg body weight) of Pb dissolved in normal saline were given to mice by oral intubation in a sub-acute (28 days) and sub-chronic (90 days) regimen followed by SFV infection. Morbidity, mortality, clinical symptoms, mean survival time (MST), changes in body and organ weight, accumulation of lead in soft tissues, virus titre in brain and histopathological alterations were compared between lead exposed and infected groups. RESULTS: Early appearance of virus symptoms, increased mortality, decreased MST, enhanced SFV titre and greater tissue damage were observed in lead exposed-SFV-infected mice. CONCLUSION: Pre-exposure to lead increases the susceptibility of mice towards SFV infection. Further studies are suggested in view of the persistence of lead in the environment and the possibility of infection by microbial pathogens.