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 examined the beneficial effect of N-acetyl cysteine (NAC) on Cd-induced nephrotoxicity. Female Sprague-Dawley rats were injected s.c. with 5 micromol CdCl2/kg per day, five times/week for up to 26 weeks. Nephrotoxicity was detected after 10 weeks by elevation in urinary lactate dehydrogenase activity and protein. NAC co-administration from week 13 prevented the progression of nephrotoxicity. In these animals, with low-level nephrotoxicity, discontinuation of Cd exposure at the end of week 22 resulted in gradual recovery over the next several weeks, without the need for treatment with NAC. On the other hand, discontinuation of NAC co-treatment at the end of week 22 resulted in quick progression of nephrotoxicity, indicating that NAC protection was short-lived. Resumption of NAC treatment and cessation of Cd exposure after 26 weeks resulted in rapid recovery from advanced nephrotoxicity. It is concluded that protection from Cd-induced nephrotoxicity is possible by continued co-administration of NAC and that recovery from advanced nephrotoxicity can also be achieved with NAC, provided that Cd exposure is stopped.