Spotting lights on genotoxicity and mutagenicity of cobalt chloride -Induced Multi-organ Dysfunction: Impact of HIF1-α/TGF-β/Smad-2/Bax/Bcl2 signaling pathways

Abstract

Abstract Cobalt chloride (CoCl2) is a ferromagnetic ubiquitous trace element that is commonly used in the production of diamonds, catalysts, and alloys. However, it might be considered a human health danger. Additionally, too much dietary cobalt can impair a variety of essential organs, which opens the door to understanding the toxicity of cobalt chloride in the liver, kidney, and cardiac tissues. To determine if the combination of arginine (Argi) and/or carnosine (Carn) can modify the expression of growth factors such Smad-2, TGF-, HIF1-, AKT mRNA, and apoptotic biomarkers Bax/ Bcl2 ratio by reducing the potentially harmful effects of cobalt chloride. Furthermore, investigate the new method by which these substances prevent Cobalt Chloride intoxication by preventing apoptosis in the target tissues. Organ poisoning was demonstrated by administering Cobalt Chloride at a dose of (60 mg/kg, SC), which was followed by treatments with Carnosine (200 mg/kg) and/or Arginine (200 mg/kg) 24 and 1 hour earlier, respectively. Hemoglobin concentration was dramatically reduced by cobalt chloride, meanwhile, protein expressions of hypoxia-inducible factor (HIF-1α), AKT, Suppressor of Mothers against decapentaplegic (Smad-2), transforming growth factor (TGF-β), and Bax/ Bcl2 ratio were elevated. Although, the combination of the fore mentioned antioxidants exerted a synergistic anti-apoptotic effect in all target tissues by the downregulation of the expression of the above-mentioned apoptotic biomarkers. It was revealed that Carn and Argi may inhibit apoptosis in response to cobalt chloride-induced poisoning through various signaling pathways.