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

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 Q10 (CoQ10), which has been shown to protect from intracellular organic arsenic, was administered separately or with DMSA; following oral exposure to sodium meta-arsenite (NaAsO2) – a very toxic trivalent form of inorganic arsenic. The aim was to determine if CoQ10 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 NaAsO2 (15 mg/kg) daily for 30 days, the third, fourth and fifth groups of mice were given NaAsO2 and treated with 200 mg/kg CoQ10 (30 days) and 50 mg/kg DMSA (5 days) either alone or in combination. Results Administration of CoQ10 and DMSA resulted in protection from arsenic-induced suppression of RBCs, haematocrit and hemoglobin levels. CoQ10 and DMSA protected from arsenic-induced alteration of WBCs, basophils, neutrophils, monocytes, eosinophils and platelets. Arsenite-induced dyslipidemia was nullified by administration of CoQ10 alone or in combination with DMSA. Arsenite induced a drastic depletion of the liver and brain GSH; that was significantly blocked by CoQ10 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 CoQ10 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 CoQ10 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 CoQ10 alongside DMSA may find applications in nullifying arsenic-driven toxicity.

Coenzyme Q10 supplementation alleviates the oxidative stress on the liver imposed by mercuric chloride in albino rats

“…Conversely, the hepatic lesions in the CoQ10+ HgCl2 co-treated rats improved more or less in line with the control group. Our findings were in agreement with those of Mwaeni et al, (2021), who discovered that oral administration of CoQ10 (200 mg/kg, for 15 days) and continued with arsenate (15 mg/kg, for a further 30 days) alleviated the elevation of biomarkers enzymes of livers and histopathological changes of hepatic tissues caused by arsenic poisoning. The degree of liver damage is connected with the intensity of intracellular and extracellular oxidative stress, which is based on an excessive synthesis of free radicals and an insufficient concentration of antioxidants (El-Sayed et al, 2015).…”

Contemporary Comprehensive Review on Arsenic-Induced Male Reproductive Toxicity and Mechanisms of Phytonutrient Intervention

“…Coenzyme-Q10 is a naturally occurring hydrophobic molecule with potent antioxidant properties that have also been found to inhibit the generation of TNF-α, NO, and NF-Kβ as well as the activation of apoptosis in rats when given at a dose of 10 mg/kg intraperitoneally for five days [189,199]. Oral administration of quercetin at a dose of 50 mg/kg for 15 days improved serum testosterone levels, restored testicular architecture, and reduced TUNEL-positive cells [191], whereas exposure for 49 days showed powerful chelating and antioxidant properties to defend against lipid peroxidation, which recovered daily sperm production, sperm count, and reversed sperm DNA damage in the epididymis and testis of rats [192,193].…”

Coenzyme Q10-Loaded Albumin Nanoparticles Protect against Redox Imbalance and Inflammatory, Apoptotic, and Histopathological Alterations in Mercuric Chloride-Induced Hepatorenal Toxicity in Rats

“…Additionally, following lead exposure, CoQ10 reversed the raised levels of serum urea and creatinine, demonstrating that it has a renal protective effect by preserving membrane integrity and preventing the leaking of these nitrogenous indicators into the bloodstream [52,53]. In other experimental models, CoQ10 decreased the increased levels of ALT, AST, ALP, creatinine, and urea mediated by piroxicam [54] and arsenic toxicity [55].…”