Protective Effects of Silymarin against Doxorubicin-induced Toxicity

Objectives: The aim of the present study was to investigate the effect of silymarin on doxorubicin-induced toxicity to the rat kidney, heart, and liver. Materials and methods: A single dose of 10 mg/kg doxorubicin was injected intraperitoneally (ip) in the doxorubicin group. The silymarin group received silymarin (100 mg/kg) every other day. In the doxorubicin + silymarin group, silymarin was injected ip at 100 mg/kg dose for 5 days before doxorubicin administration (10 mg/kg, single ip injection) and then continued daily thereafter until euthanization. On the seventh day after doxorubicin injection, eight animals from each group were decapitated and liver and heart samples were obtained. The remaining eight animals of each group continued to receive silymarin every other day, till euthanized on the twenty first day. Serum was separated for determination of superoxide dismutase (SOD), glutathione peroxidase (GSHPx), catalase (CAT), malondialdehyde (MDA), nitric oxide (NO), creatinine, urea, AST, ALT, lactate dehydrogenase (LDH) and creatinine phosphokinase (CPK) activities. Histopathological and electron microscopic examinations of heart, kidney and liver sections were also performed. Results: Doxorubicin caused a significant increase in serum NO levels compared to controls. Silymarin pretreatment group lowered these. Histopathological and electron microscopic examinations of kidney, heart, and liver sections showed doxorubicin to cause myocardial and renal injury which was levv evident in silymarin treated rats. Conclusion(s): Results of the present study indicate that silymarin significantly protected doxorubicin-induced toxicities to the rat kidney, heart, and liver, thus suggesting its administration as a supportive care agent during anti-cancer treatment featuring doxorubicin

Evaluating the effect of peroral bentonite administration on iron disposition and mortality in rat model of acute iron toxicity.

Activated charcoal lacks efficacy in preventing the absorption of iron. We hypothesized that bentonite, which is an inert natural adsorbent, may decrease the iron absorption and ameliorate the toxic manifestations in rats after iron poisoning. For the pharmacokinetic experiments, rats were randomized into three groups which received iron (as ferrous sulfate)+distilled water (Control), iron+bentonite (B5(five- fold higher than the iron dose)), iron+bentonite (B10 (ten-fold higher than the iron dose)) via gavage. The blood samples were taken for six hours. The area under the plasma concentration-time curve (AUC) (0-360) (min mu g/dl), peak concentration of iron in serum (Cmax) and time to reach Cmax (tmax) were calculated from the individual serum concentration-time profiles. For the survival part, rats were randomized into three groups and received (LD50), iron+distilled water (Control (s)), iron+bentonite (Bs5 (fivefold bentonite)) and iron+bentonite (Bs10) via gavage. Rats were observed for 72 hours. Iron levels showed a wide variation, and no significant differences in AUC (0-360), Cmax and tmax were detected. However, the mortality rate was significantly lower (9.1%) in the Bs10 group, as compared to Control (s) (55.6%) groups. Bentonite was found to be effective in preventing mortality in the rat model of acute iron toxicity