Renal Handling of Cephalosporins

However, cortical concentration does not appear to be the sole determinant of toxicity for other cephalosporin antibiotics, since several cephalosporins reach high cortical concentrations without producing nephrotoxicity. For example, both cepha-loglycin and cephaloridine produce nephrotoxicity whereas cephalexin is not nephrotoxic. Cortical concentrations of cephaloridine, cephaloglycin, and cephalexin are approximately equal initially (0-2 hr) following treatment with these antibiotics. While cortical cephaloridine concentration does not decline, cortical concentrations of both cephaloglycin and cephalexin decline in a similar fashion over 3 hr. Thus, 

In vitro exposure of renal cortical slices to cephaloridine results in time- and concentration-dependent increases in lipid peroxidation, as reflected by malondial-dehyde production. Furthermore, the onset of cephaloridine-induced malondial-dehyde production preceded cephaloridine-induced inhibition of organic ion accumulation, suggesting that cephaloridine-induced lipid peroxidation mediates the effects of cephaloridine on organic ion transport. Additionally, antioxidants (e.g., promethazine, N, A -diphenyl-p-phenylenediamine) block the effects of cephaloridine on lipid peroxidation and on organic ion transport, suggesting a cause-effect relationship between cephaloridine-induced lipid peroxidation and inhibition of organic ion transport. 

Chloroform is a nephrotoxicant that most likely undergoes metabolic bioactivation within the kidney. Chloroform (CHC13), a common organic solvent widely used in the chemical industry, produces hepatic and renal injury in humans and experimental animals. Renal necrosis due to chloroform is sex- and species-specific For example, male mice exhibit primarily renal necrosis whereas female mice develop 

Kidneys have relatively low xenobiotic-metabolizing enzyme activities, and chemically induced nephrotoxicity has been assumed to be produced by toxic intermediates generated in the liver and transported to the kidney. If a single hepatic metabolite of chloroform produced both kidney and liver injury, species, strain, and sex differences in susceptibility to chloroform nephro- and hepatotoxicity should be similar. However, species, strain and sex differences in susceptibility to chloroform nephrotoxicity are not consistent with those of chloroform hepatotoxicity. In addition, several modulators of tissue xenobiotic-metabolizing activities alter 

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