Cis-Diammine Dichloroplatinum nephrotoxicity in rats and its prevention by diallyldisulfide

CASTRO JA; CHIARANDINI FIORE JP; CIGNOLI DE FERREYRA EC; FANELLI SL.

Palais des Congrès de Montréal , Montreal, Canadá.

Congreso; Eleventh International Congress of Toxicology (IUTOX) ICTXI; 2007

International Union of Toxicology

Cis-diammine dichloroplatinum (CisPt) is an effective chemotherapeutic agent against several human cancers but it produces important nephrotoxicity. In this work we analyze the possibility that diallyldisulfide (DADS) could block this toxicity. Four groups of male Sprague Dawley rats were used (control, DADS control, CisPt and CisPt + DADS). CisPt was administered subcutaneously as a single dose (10.5 mg/kg) in saline. The DADS was administered daily intragastrically in olive oil (292.5 mg/kg) .The animals were sacrificed 5 days after CisPt administration. Serum creatinine and urea determinations were performed and samples of kidneys were taken for histological and for t-butylhydroperoxide promoted chemiluminiscence studies. DADS significantly decreased mortality and blocked CisPt nephrotoxicity. CisPt renal toxicity involved the production of oxygen reactive species (ROS); DADS blocked ROS production without changing Pt levels in kidney. In hands of other laboratories, DADS exhibited an ability to inhibit cellular replication and to promote apoptosis of tumoral cells and thus, we envisage a potential application of DADS as adjuvant of CisPt chemotherapy. Supported by CONICET and UNSAM.