Treatment of chronic cadmium nephrotoxicity by N-acetyl cysteine

Chronic cadmium (Cd)-induced nephrotoxicity is believed to be irreversible at advanced stages and no treatment is currently available. This study exam ined the beneficial effect of N-acetyl cysteine (NAC) on Cd-induced nephrot oxicity. Female Sprague-Dawley rats were injected sc with 5 mu mol CdCl2/kg per day, five times/week for up to 26 weeks. Nephrotoxicity was detected a fter 10 weeks by elevation in urinary lactate dehydrogenase activity and pr otein. NAC co-administration from week 13 prevented the progression of neph rotoxicity. In these animals, with low-level nephrotoxicity, discontinuatio n of Cd exposure at the end of week 22 resulted in gradual recovery over th e next several weeks, without the need for treatment with NAG. On the other hand, discontinuation of NAC co-treatment at the end of week 22 resulted i n quick progression of nephrotoxicity, indicating that NAC protection was s hort-lived. Resumption of NAC treatment and cessation of Cd exposure after 26 weeks resulted in rapid recovery from advanced nephrotoxicity. It is con cluded that protection from Cd-induced nephrotoxicity is possible by contin ued co-administration of NAC and that recovery from advanced nephrotoxicity can also be achieved with NAG, provided that Cd exposure is stopped. (C) 1 999 Elsevier Science Ireland Ltd. All rights reserved.