In vivo antioxidant and antigenotoxic evaluation of an enaminone derivative BDHQ combined with praziquantel in uninfected and Schistosoma mansoni infected mice

Chemotherapy with praziquantel is the cornerstone of schistosomiasis control, but an oxidative/nitrative stress may occur after short-term treatment and participate in side effects. The aim of this study was to evaluate the antioxidant and antigenotoxic effects of the novel antischistosomal enaminone derivative, 4a"hydroxyquinoline (BDHQ), alone or combined with PZQ, in hepatic tissues of uninfected and Schistosoma mansoni infected mice. Uninfected untreated control mice and infected mice were treated with 0 or 500 mg/kg PZQ, 600 mg/kg BDHQ, or PZQ (250 mg/kg) combined with BDHQ (300 mg/kg) for 2 consecutive days. The studied biomarkers, related to oxidative/nitrosative stress and DNA damage were significantly improved in infected mice treated with BDHQ combined with PZQ as compared to either drug alone. This amelioration was accompanied with reduction in hepatic granuloma size and histopathologic lesions. Furthermore, we documented a novel PZQ-induced mutation of hepatic mitochondrial genome in uninfected animals.