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. 2023 Jul 13;9(8):FSO874.
doi: 10.2144/fsoa-2023-0050. eCollection 2023 Sep.

Impact of HIF1-α/TGF-β/Smad-2/Bax/Bcl2 pathways on cobalt chloride-induced cardiac and hepatorenal dysfunction

Mai O Kadry  1 , Hanaa Mahmoud Ali  2
Affiliations

Impact of HIF1-α/TGF-β/Smad-2/Bax/Bcl2 pathways on cobalt chloride-induced cardiac and hepatorenal dysfunction

Mai O Kadry et al. Future Sci OA. .

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.

Keywords: AKT; Bax/Bcl2 ratio; HIF1-α; Smad-2; TGF-β; cobalt chloride.

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.

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Conflict of interest statement

Conflicts of interest disclosure The authors declare that there are no conflicts of interest present.

Figures

Figure 1.
Figure 1.. (A–C) Representative immunoblots (Western blot analysis) of hepatic Bax, Bcl 2, and Smad-2 in control and different treated groups.
Figure 2.
Figure 2.. (A–C) Representative immunoblots (Western blot analysis) of hepatic TGF-β, HIF1-α, and AKT in control and different treated groups.
Figure 3.
Figure 3.. Impact of Arginine (AR), Carnosine (CR) and their combination on AKT, Smad-2, HIF1-α, TGF-β, Bax and Bcl2 protein expression post CoCl2 induced liver toxicity.
Data are expressed as mean ± S.E.M (n = 10). p ≤ 0.05 value is considered significant. Groups having the same letter are not significantly different from each other, while those having different letters are significantly different from each other.
Figure 4.
Figure 4.. (A–C) Representative immunoblots (Western blot analysis) of renal Bax, Bcl 2, and Smad-2 in control and different treated groups.
Figure 5.
Figure 5.. (A–C) Representative immunoblots (Western blot analysis) of renal TGF-β, HIF1-α, and AKT in control and different treated groups.
Figure 6.
Figure 6.. Impact of Arginine (AR), Carnosine (CR) and their combination on AKT, Smad-2, HIF1-α, TGF-β, Bax and Bcl2 protein expression post CoCl2 induced kidney toxicity.
Data are expressed as mean ± S.E.M (n = 10). p ≤ 0.05 value is considered significant. Groups having the same letter are not significantly different from each other, while those having different letters are significantly different from each other.
Figure 7.
Figure 7.. (A–C) Representative immunoblots (Western blot analysis) of cardiac Bax, Bcl 2, and Smad-2 in control and different treated groups.
Figure 8.
Figure 8.. (A–C) Representative immunoblots (Western blot analysis) of cardiac TGF-β, HIF1-α, and AKT in control and different treated groups.
Figure 9.
Figure 9.. Impact of Arginine (AR), Carnosine (CR) and their combination on AKT, Smad-2, HIF1-α, TGF-β, Bax and Bcl2 protein expression post CoCl2 induced heart toxicity.
Data are expressed as mean ± S.E.M (n = 10). p ≤ 0.05 value is considered significant. Groups having the same letter are not significantly different from each other, while those having different letters are significantly different from each other.
See this image and copyright information in PMC

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