Abstract

Background: Chemotherapy with praziquantel is the cornerstone of schistosomiasis control, but an oxidative/nitrative stress may occur after a short-term treatment and participate in side effects. It was recommended that the drug must be re-evaluated because of its potential carcinogenicity and genotoxicity. Therefore, the aim of this study is to evaluate the antioxidant and genotoxic effects of the novel antischistosomal enaminone derivative of 4–hydroxyquinoline, BDHQ, alone or combined with PZQ in hepatic tissues of uninfected and Schistosoma mansoni challenged mice.
Methodology/Principal Findings: Eight groups of mice were used in this study. The first group represented the uninfected untreated control. The second group was infected with 50±10 S. mansoni cercariae. Groups (3-5) were also infected and treated with PZQ (500 mg/kg), BDHQ (600 mg/kg) and PZQ (250 mg/kg) combined with BDHQ (300 mg/kg) for 2 consecutive days 6 weeks post-infection (PI), respectively. Groups (6-8) included comparable uninfected treated animals. The mice in each group were evaluated 7 and 9 PI. At the end of the experimental period, liver tissues were harvested for measuring level of oxidative/nitrosative stress, fragmented DNA, mtDNA mutagenicity, and histopathological examination in hepatic tissues.
The studied biomarkers, related to oxidative/nitrosative stress and DNA damage were significantly improved in infected mice treated with BDHQ combined with PZQ more than does either drug alone compared with infected untreated one. This amelioration is accompanied with reduction in hepatic granuloma size and elevation in nitric oxide production as well as absence of histopathological lesions in hepatic tissue. Furthermore, we reported a novel PZQ-induced mutation of D-loop fragment of hepatic mitochondrial genome in healthy animals.
Conclusions/Significance: Our results suggested a protective role of BDHQ, against S. mansoni induced oxidative stress and genotoxicity in hepatic tissues of mice, especially when combined with PZQ. Also, protection against mtDNA mutation is potential areas for new therapeutics.

Key words: Schistosomiasis; praziquantel; BDHQ; mtDNA; point mutation; nitrosative stress