Different effects of (CIS+TRANS) 1,3-dichloropropene in renal cortical slices derived from male and female rats

1 Nephrotoxic effects of 1,3-dichloropropene (cis and trans isomers mixture ) was investigated in vitro by means of renal cortical slice model in male and female rats, including treatment with metabolism modifiers as an induce r of cytochrome P-450 1A class (beta-naphthoflavone), a reduced glutathione depleting (DL-buthionine-[S,R]-sulfoximine), an inhibitor of gamma-glutamy ltransferase (AT-125) and inhibitor of cysteine conjugate beta-lyase (amino oxiacetic acid). 2 Dose-dependent decrease of p-aminohippurate uptake was observed in male r enal cortical slices. Only the high doses (3.0 and 4.0 x 10 (4) M) caused a significant loss of organic anion uptake in females. 3 beta-Naphthoflavone and 5-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic ac id (AT-125) partially, but significantly, reduced organic anion loss in mal es. In females, DL-buthionine-[S,R]-sulfoximine significantly increased in females but in males loss of organic anion accumulation caused by 1,3-dichl oropropene. Aminooxyacetic acid did not ameliorate 1,3 D effects in vivo an d in vitro in male rats. It appeared very toxic for female rats (all rats d ied) after in vivo injection. 4 Sensitivity to nephrotoxicity induced by I,3-dichloropropene in vitro was about double in male than female rats. Reduced glutathione conjugation app eared involved in nephrotoxicity induced in males but in females, probably by means of a chloropropyl-cysteinylglycine-conjugate formation; slight tox icity in females is likely related to oxidative metabolism.