Dihydroxy-isosteviol-methyl-ester, an active biological component of Pulsatilla nigricans, reduces arsenic induced cellular dysfunction in testis of male mice.

Arsenic contamination has become a menacing health concern, warranting search for new drugs capable of ameliorating its toxicity. Extract of Pulsatilla nigricans is occasionally used as traditional medicine including homeopathy to combat/alleviate toxicity-related symptoms of known or unknown cause. Mice were intoxicated with a sub-lethal dose of sodium arsenite (20mg/kg b.w./day, determined through a range-finding trial) and the effect on testicular toxicity after 30, 60, and 90 days was examined. We observed an increased level of reactive oxygen species, cellular damage in testes of SA-intoxicated mice and further analysed expressions of apoptotic signal proteins and mRNA like Bax, Bcl2 and caspase3. Treatment with EEPN showed significant inhibition/reversal of the arsenic-induced toxic effect in testis and reduced oxidative stress through modulating expressions of signal proteins, thereby inhibiting the progression of events of apoptosis in testis cells and sperm. Therefore, EEPN has potentials for therapeutic use in arsenic- induced reproductive toxicity.

The marginalization of hormesis.

Despite the substantial development and publication of highly reproducible toxicological data, the concept of hormetic dose-response relationships was never integrated into the mainstream of toxicological thought. Review of the historical foundations of the interpretation of the bioassay and assessment of competitive theories of dose-response relationships lead to the conclusion that multiple factors contributed to the marginalization of hormesis during the middle and subsequent decades of the 20th Century. These factors include the following: (a) the close association of hormesis with homeopathy, which led to the hostility of modern medicine toward homeopathy, thereby creating a guilt-by-association framework, and the carryover influence of that hostility toward hormesis in the judgements of medically based pharmacologists/toxicologists; (b) the emphasis of high-dose effects linked with a lack of appreciation of the significance of the implications of low-dose stimulatory effects; (c) the lack of an evolution-based mechanism(s) to account for hormetic effects; and (d) lack of appropriate scientific advocates to counter aggressive and intellectually powerful critics of the hormetic perspective.