Ameliorative Effects of Coadministered Coenzyme Q10 And Dimercaptosuccinic Acid on Arsenic-Induced Toxicity in a Mouse Model

Abstract

Exposure to arsenic is a growing human health threat to millions of people globally. Dimercaptosuccinic Acid (DMSA), the current treatment drug, chelates extracellularly distributed arsenic, allowing the intracellular arsenic to persist and get metabolized to toxic by-products. Previous studies on Coenzyme Q10 (CoQ10) have demonstrated remarkable protective roles against organic forms of arsenic. So far, no studies have determined if coadministered CoQ10 and DMSA can protect from inorganic forms of arsenic. Therefore, this study was conducted to evaluate the ameliorative effect of coadministered DMSA and Coenzyme Q10 on inorganic arsenite-induced toxicity in male Swiss albino mice. Male mice were exposed to sodium arsenite (15mg/kg) then either maintained on drinking water or treated. Treated mice received 50mg/kg DMSA (5 days) and 200mg/kg CoQ10 (30 days) either singly or in combination. Mice were subjected to weekly weight measurement and Rapid Murine Behavioral Coma scoring tests (RMBC). After 30 days’ post treatment mice were sacrificed and samples obtained for analysis. Further hematological and biochemical parameters as well as inflammatory and histopathological profiles were determined. Data collected was analyzed using One-Way ANOVA with Tukey’s post hoc test for pairwise comparisons. Coadministered CoQ10 and DMSA significantly protected mice from arsenite-induced weight loss. Further, exposure to arsenite resulted in a significant reduction of Hematocrit, Red blood cells concentration, and hemoglobin. Treatment with CoQ10 and DMSA either alone or in combination prevented the suppression of the Hematocrit, Red blood cells and hemoglobin levels following arsenite exposure. Further, arsenite caused an increase in White blood cell (WBC) count and basophils with a decrease in the neutrophils, monocytes, and eosinophils. Coadministered CoQ10 and DMSA prevented arsenite-induced changes in WBC and differential count. Mice exposed to arsenite had high cholesterol, triglyceride, and high density lipoprotein levels. Coenzyme Q10, and DMSA, significantly protected mice from arsenite-induced alterations of the lipid profiles. This study demonstrated arsenic-driven oxidative stress in the liver, brain, lungs, spleen, and heart indicated by drastic depletion of (Reduced Glutathione) GSH. Administered CoQ10 protected mice from arsenic-induced depletion of GSH. Elevation of liver (Aspartate aminotransferase, Alanine aminotransferase, Gamma glutamyl transferase, bilirubin) and kidney (Creatinine) markers further demonstrated the possible injury due to arsenite exposure. Investigations of liver, kidney, and brain tissue sections also confirmed this finding. It was noted that CoQ10 blocked those adverse events more efficiently than DMSA. Moreover, arsenic-induced inflammation was evident by the elevation of Interferon- gamma (INF- and Tumor necrosis factor-alpha (TNF-, with concomitant depletion of anti-inflammatory marker Interleukin -10 (IL-10). The remarkable finding from this study is that treatment with CoQ10 and DMSA was effective in countering oxidative stress and inflammation than DMSA alone that showed no protection against organ injury. Findings from this study provide an alternative avenue for developing new strategies to improve the treatment and management of arsenic-induced toxicity.