Coenzyme Q10 protected against arsenite and enhanced the capacity of 2,3-dimercaptosuccinic acid to ameliorate arsenite-induced toxicity in mice

Abstract

Abstract Background Arsenic poisoning affects millions of people. The inorganic forms of arsenic are more toxic. Treatment for arsenic poisoning relies on chelation of extracellularly circulating arsenic molecules by 2,3-dimecaptosuccinic acid (DMSA). As a pharmacological intervention, DMSA is unable to chelate arsenic molecules from intracellular spaces. The consequence is continued toxicity and cell damage in the presence of DMSA. A two-pronged approach that removes extracellular arsenic, while protecting from the intracellular arsenic would provide a better pharmacotherapeutic outcome. In this study, Coenzyme Q 10 (CoQ 10 ), which has been shown to protect from intracellular organic arsenic, was administered separately or with DMSA; following oral exposure to sodium meta-arsenite (NaAsO 2 ) – a very toxic trivalent form of inorganic arsenic. The aim was to determine if CoQ 10 alone or when co-administered with DMSA would nullify arsenite-induced toxicity in mice. Methods Group one represented the control; the second group was treated with NaAsO 2 (15 mg/kg) daily for 30 days, the third, fourth and fifth groups of mice were given NaAsO 2 and treated with 200 mg/kg CoQ 10 (30 days) and 50 mg/kg DMSA (5 days) either alone or in combination. Results Administration of CoQ 10 and DMSA resulted in protection from arsenic-induced suppression of RBCs, haematocrit and hemoglobin levels. CoQ 10 and DMSA protected from arsenic-induced alteration of WBCs, basophils, neutrophils, monocytes, eosinophils and platelets. Arsenite-induced dyslipidemia was nullified by administration of CoQ 10 alone or in combination with DMSA. Arsenite induced a drastic depletion of the liver and brain GSH; that was significantly blocked by CoQ 10 and DMSA alone or in combination. Exposure to arsenite resulted in significant elevation of liver and kidney damage markers. The histological analysis of respective organs confirmed arsenic-induced organ damage, which was ameliorated by CoQ 10 alone or when co-administered with DMSA. When administered alone, DMSA did not prevent arsenic-driven tissue damage. Conclusions Findings from this study demonstrate that CoQ 10 and DMSA separately or in a combination, significantly protect against arsenic-driven toxicity in mice. It is evident that with further pre-clinical and clinical studies, an adjunct therapy that incorporates CoQ 10 alongside DMSA may find applications in nullifying arsenic-driven toxicity.

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