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

Overview

Journal Future Sci OA

Specialty Biotechnology

Date 2023 Aug 25

PMID 37621844

Authors

Mai O Kadry

Hanaa Mahmoud Ali

Affiliations

Soon will be listed here.

Abstract

Background: Cobalt chloride (CoCl) 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 CoCl on the liver, kidney and heart.

Method: CoCl 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 CoCl-intoxication.

Results: CoCl 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.

References

Bradford M . A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72:248-54. DOI: 10.1016/0003-2697(76)90527-3. View

Sandner P, Wolf K, Bergmaier U, Gess B, Kurtz A . Induction of VEGF and VEGF receptor gene expression by hypoxia: divergent regulation in vivo and in vitro. Kidney Int. 1997; 51(2):448-53. DOI: 10.1038/ki.1997.60. View

Li W, Sun K, Hu F, Chen L, Zhang X, Wang F . Protective effects of natural compounds against oxidative stress in ischemic diseases and cancers via activating the Nrf2 signaling pathway: A mini review. J Biochem Mol Toxicol. 2020; 35(3):e22658. DOI: 10.1002/jbt.22658. View

Tapiero H, MATHE G, Couvreur P, Tew K . I. Arginine. Biomed Pharmacother. 2002; 56(9):439-45. DOI: 10.1016/s0753-3322(02)00284-6. View

Aldini G, de Courten B, Regazzoni L, Gilardoni E, Ferrario G, Baron G . Understanding the antioxidant and carbonyl sequestering activity of carnosine: direct and indirect mechanisms. Free Radic Res. 2020; 55(4):321-330. DOI: 10.1080/10715762.2020.1856830. View

Karakka Kal A, Perwad Z, Karatt T, Nalakath J, Subhahar M . Using Inductively Coupled Plasma Mass Spectrometry to Assess Essential and Performance-Enhancing Metals in the Urine of Racehorses. J Anal Toxicol. 2020; 44(5):490-498. DOI: 10.1093/jat/bkaa004. View

Wang Z, Zhao G, Issotina Zibrila A, Li Y, Liu J, Feng W . Acetylcholine ameliorated hypoxia-induced oxidative stress and apoptosis in trophoblast cells via p38 MAPK/NF-κB pathway. Mol Hum Reprod. 2021; 27(8). DOI: 10.1093/molehr/gaab045. View

Lugun O, Singh J, Thakur R, Pandey A . Cobalt oxide (Co3O4) nanoparticles induced genotoxicity in Chinese hamster lung fibroblast (V79) cells through modulation of reactive oxygen species. Mutagenesis. 2022; 37(1):44-59. DOI: 10.1093/mutage/geac005. View

Oyagbemi A, Akinrinde A, Adebiyi O, Jarikre T, Omobowale T, Ola-Davies O . Luteolin supplementation ameliorates cobalt-induced oxidative stress and inflammation by suppressing NF-кB/Kim-1 signaling in the heart and kidney of rats. Environ Toxicol Pharmacol. 2020; 80:103488. DOI: 10.1016/j.etap.2020.103488. View

10.

Kong D, Zhang F, Shao J, Wu L, Zhang X, Chen L . Curcumin inhibits cobalt chloride-induced epithelial-to-mesenchymal transition associated with interference with TGF-β/Smad signaling in hepatocytes. Lab Invest. 2015; 95(11):1234-45. DOI: 10.1038/labinvest.2015.107. View

11.

Mahdavi Gorabi A, Kiaie N, Hajighasemi S, Banach M, Penson P, Jamialahmadi T . Statin-Induced Nitric Oxide Signaling: Mechanisms and Therapeutic Implications. J Clin Med. 2019; 8(12). PMC: 6947613. DOI: 10.3390/jcm8122051. View

12.

Kirkland D, Brock T, Haddouk H, Hargeaves V, Lloyd M, Mc Garry S . New investigations into the genotoxicity of cobalt compounds and their impact on overall assessment of genotoxic risk. Regul Toxicol Pharmacol. 2015; 73(1):311-38. DOI: 10.1016/j.yrtph.2015.07.016. View

13.

Bailey J, Diotallevi M, Nicol T, McNeill E, Shaw A, Chuaiphichai S . Nitric Oxide Modulates Metabolic Remodeling in Inflammatory Macrophages through TCA Cycle Regulation and Itaconate Accumulation. Cell Rep. 2019; 28(1):218-230.e7. PMC: 6616861. DOI: 10.1016/j.celrep.2019.06.018. View

14.

Qin C, Yang S, Chu Y, Zhang H, Pang X, Chen L . Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions. Signal Transduct Target Ther. 2022; 7(1):215. PMC: 9259607. DOI: 10.1038/s41392-022-01064-1. View

15.

Garoui E, Troudi A, Fetoui H, Soudani N, Boudawara T, Zeghal N . Propolis attenuates cobalt induced-nephrotoxicity in adult rats and their progeny. Exp Toxicol Pathol. 2011; 64(7-8):837-46. DOI: 10.1016/j.etp.2011.03.004. View

16.

Tong Y, Tong K, Zhu Q, Wu Y, Yang Y, Zhang J . Cobalt Chloride Induced Apoptosis by Inhibiting GPC3 Expression via the HIF-1α/c-Myc Axis in HepG2 Cells. Onco Targets Ther. 2019; 12:10663-10670. PMC: 6901039. DOI: 10.2147/OTT.S227215. View

17.

Czarnek K, Terpilowska S, Siwicki A . Selected aspects of the action of cobalt ions in the human body. Cent Eur J Immunol. 2015; 40(2):236-42. PMC: 4637398. DOI: 10.5114/ceji.2015.52837. View

18.

Feehan J, Hariharan R, Buckenham T, Handley C, Bhatnagar A, Baba S . Carnosine as a potential therapeutic for the management of peripheral vascular disease. Nutr Metab Cardiovasc Dis. 2022; 32(10):2289-2296. DOI: 10.1016/j.numecd.2022.07.006. View

19.

Maliyur Basavaraju A, Shivanna N, Yadavalli C, Garlapati P, Kandangath Raghavan A . Ameliorative Effect of Ananas comosus on Cobalt Chloride-Induced Hypoxia in Caco2 cells via HIF-1α, GLUT 1, VEGF, ANG and FGF. Biol Trace Elem Res. 2020; 199(4):1345-1355. DOI: 10.1007/s12011-020-02278-6. View

20.

Oyagbemi A, Ajibade T, Esan O, Adetona M, Obisesan A, Adeogun A . Naringin abrogates angiotensin-converting enzyme (ACE) activity and podocin signalling pathway in cobalt chloride-induced nephrotoxicity and hypertension. Biomarkers. 2022; 28(2):206-216. DOI: 10.1080/1354750X.2022.2157489. View