Sex- and age-related nephrotoxicity due to 1,2-dichloropropane in vitro

Abstract

Sex- and age-related nephrotoxicity due to 1,2-dichloropropane was studied in vitro by means of renal cortical slices obtained from Wistar rats. Reduced glutathione content, organic anion accumulation (p-aminohippurate), and release of malondialdehyde (to measure the extent of lipid peroxidation), aspartate aminotransferase, gamma-glutamyltransferase and lactate dehydrogenase into the incubation medium were determined. Sex differences in naive rats parameters were slight, but male were more susceptible to toxic effects of 1,2-dichloropropane than female rats; glutathione depletion, lipid peroxidation, and loss of organic anion accumulation were higher in male than in female slices. During senescence, naive male rats showed a progressive decrease of glutathione content (statistically significant from 7-9 months of age), increase of spontaneous lipid peroxidation from the same age, and increase of signs of cytotoxicity (release of aspartate aminotransferase and lactate dehydrogenase into the incubation medium) from 3-4 months of age. A loss of organic anion accumulation started from 7-9 months of age. Slices from rats of 3-4 months old showed the apparently highest susceptibility to 1,2-dichloropropane but depletion of glutathione content and loss of organic anion accumulation were at the same level in the oldest rats. The age decrease of control values caused the differences in the percentage ratio and then, apparently, a lower DCP effect. On the contrary, the increase of aspartate aminotransferase released in the incubation medium by DCP-treated slices corresponded to the age-related increase in cytotoxicity.

Sex-related differences in renal toxicodynamics in rodents

“…1,2-Dichloropropane causes nephrotoxic effects via mercapturic acid metabolism [109]. In vitro, renal cortical slices prepared from male Wistar rat kidney were more sensitive to DCP effects than those from females [110]. Further, in a classic sex hormone paradigm study, Odinecs et al [111] confirmed that male rats are more sensitive than females and that testosterone plays a pivotal role in nephrotoxicity.…”