Cis-diammine dichloroplatinum nefrotoxicity in rats. Prevention by Diallyldisulfide

CHIARANDINI FIORE J.P; CIGNOLI DE FERREYRA E.C.; FANELLI S.L.; CASTRO J.A

Córdoba

Congreso; XXXVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental (SAFE); 2006

Sociedad Argentina de Farmacología Experimental (SAFE),

Cis-diammine dichloroplatinum (CisPt) is an effective chemotherapeutic agent against several human cancers but it produces important nephrotoxicity. In this work we analize the possibility that the diallyldisulfide (DADS) could block this toxicity without risk or enhancement of this therapeutic. 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. Seric creatinine and urea determinations were performed and samples of kidneys were taken for histological and 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.