Impact of HIF1-α/TGF-β/Smad-2/Bax/Bcl2 Pathways on Cobalt chloride-induced Cardiac and Hepatorenal Dysfunction

Abstract

Background: Cobalt chloride (CoCl₂) is a ferromagnetic ubiquitous trace element extensively dispersed in the environment. Nevertheless, it may merit human hazard. Aim: Excess cobalt can harm vital organs this paves the way to elucidate the toxic impact of CoCl₂ on the liver, kidney and heart. Method: CoCl₂ was injected in a dose of (60 mg/kg, S.C.) proceeded via Carnosine (200 mg/kg) and/or Arginine (200 mg/kg) treatment 1 month, 24 and 1 h, prior to CoCl₂-intoxication. Results: CoCl₂ significantly alleviated hemoglobin concentration and BCl2; meanwhile, protein expression of transforming growth factor (TGF-β), hypoxia-inducible factor (HIF-1α), Mothers against decapentaplegic (Smad-2), AKT protein expression and Bax/Bcl2 ratio was noticeably elevated. Conclusion: The combination of the aforementioned antioxidants exerted a synergistic anti-apoptotic impact in all target tissues.

Plain Language Summary

Cobalt chloride (CoCl₂) is commonly found in the environment and used in medicine. However, it can be harmful to our health, particularly when consumed in excessive amounts, leading to damage in important organs. Therefore, we investigated the toxic effects of CoCl₂ on the liver, kidney, and heart. We also explored potential treatments using substances like Carnosine and Arginine. We discovered that Arginine and carnosine had a positive effect on certain factors related to the health of the organs. They helped regulate the levels of hemoglobin and BCl2, as well as the expression of proteins such as transforming growth factor (TGF-β), hypoxia-inducible factor (HIF-1α), Mothers against decapentaplegic (Smad-2), AKT, and apoptotic biomarkers like the Bax/Bcl2 ratio. When these antioxidants were combined, they had a stronger protective effect against cell death and mutations in all the organs studied.

Keywords:

• AKT
• Bax/Bcl2 ratio
• cobalt chloride
• HIF1-α
• Smad-2
• TGF-β

Author contributions

All the authors are responsible for writing the contents in this article and jointly contributed to the study conception and design, writing of introduction, methodology, discussion, conclusion, recommendations, future perspective, executive summary, appropriate referencing and protocols, the literature review search, research, data collection, data analysis, data interpretation, result presentation and approval of the final version of this article.

Acknowledgments

Authors are grateful for the National Research center for all the facilities and tools provided.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

Adult male albino Wister rats (200–220 g) were obtained from the Animal House at the National Research Centre The Animal Experimental protocol was approved by the Experimental Animal Ethics Committee of the National Research Center, Egypt under no. 24512012023.