Veterinary Research Forum

Protective effects of melatonin against hypoxia-induced TM3 cell damage via suppression of the TGF-β pathway

Document Type : Original Article

Authors

Sahar Rashidi 1
Adel Saberivand 1
Mohammadreza Gholami 2
Vahideh Asadollahi 3
Masoud Alasvand 4
Maryam Saberivand 5
Mona Ghasemi 1

1 Department of Clinical Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran

2 Medical Technology Research Center, Institute of Health Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran

3 Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

4 Cancer and Immunology Research Center, Research Institute for Health Development, Kurdistan University of Medical Science, Sanandaj, Iran

5 Connective Tissue Diseases Research Center, Tabriz University of Medical Science, Tabriz, Iran

https://doi.org/10.30466/vrf.2024.2039638.4415
Abstract
This study aimed to explore whether melatonin protects TM3 Leydig cells from cobalt (II) chloride (CoCl2)-induced hypoxia through the transforming growth factor beta (TGF-β) signaling pathway. Cells were divided into four groups: a control group without treatment (Group 1), a melatonin group (10.00 ng mL-1; Group 2), a group treated with CoCl2 (100 µM) to induce hypoxia (Group 3), and a melatonin + CoCl2 group (Group 4). After 96 hr of incubation, cell viability was assessed using the MTT assay, and transforming growth factor beta 1, activin receptor-like kinase-5, and bone morphogenetic protein 4 gene and protein expressions were measured through RT‑PCR and western blotting. The CoCl2 and melatonin + CoCl2 groups exhibited significantly diminished cell viability compared to the control. However, melatonin treatment enhanced survival in the CoCl2-exposed cells. Notably, transforming growth factor beta 1 expression was elevated in all groups. Activin receptor-like kinase-5 (gene and protein expression increased in CoCl2-treated groups but was lower in the melatonin + CoCl2 group. Melatonin treatment reduced bone morphogenetic protein 4 expression compared to the control, while CoCl2 groups showed increased bone morphogenetic protein 4 levels. These findings suggest melatonin's potential as a therapeutic agent against oxidative stress and hypoxia in TM3 cells through its antioxidant properties.

Keywords

Cobalt (II) chloride
Leydig cells
Melatonin
TGF-&beta
signaling pathway
Subjects
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Veterinary Research Forum
Volume 17, Issue 3
March 2026
Pages 145-152

  • Receive Date 26 August 2024
  • Revise Date 25 December 2024
  • Accept Date 30 December 2024

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