Toxicoproteomics

The opportunity to discover new markers of impending toxic side effects is ready to be exploited by existing proteomic technology (55). Some work has already been done in this area: Fountoulakis et al. (56) characterized the effects of xenobiotics on protein expression in rodent liver, in an attempt to define a liver proteomic toxicity database; a further study on hepatic protein changes associated with a number of drug treatments was carried out by Man et al. (57). Similar analyses have been carried out for specific compounds, such as the hepatotoxic effects of substituted pyrimidine derivatives (58) or nephrotoxicity in antimicrobial agents, such as gentamycin (59), and cyclosporin A

(60). ICRF187, a cardio-protectant, has been shown to suppress a significant number of protein alterations in the serum of rats treated with cardiotoxic levels of doxorubicin

(61), suggesting key protein markers of cardiotoxicity. The elucidation of markers affected by protective drugs may give functional hints as to the mechanism of protection, accelerating the development of more effective agents.

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