Biochemical interactions and nephrotoxicity.

To understand the nephrotoxicity of xenobiotics, the species, strain, sex, and the presence of other chemicals must be considered. This review has considered the importance of these factors in determining the nephrotoxic liability of a drug. For example, cephaloridine is more nephrotoxic in rabbit than rats and is least nephrotoxic in mice. This species-dependent susceptibility to cephaloridine nephrotoxicity appears to be related to the degree in which cephaloridine depletes renal cortical glutathione. Additionally, only male mice of certain strains are susceptible to chloroform-induced nephrotoxicity. Lastly, the presence of certain ketones or ketogenic substances such as acetone and hexane enhance chloroform-induced nephrotoxicity in male Sprague-Dawley rats. Knowing which factors can enhance or limit nephrotoxicity of drugs will lend to a better understanding of the mechanism of these toxicities as well as to design compounds with lesser toxicities.