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1,25-Dihydroxycholecalciferol down-regulates 3-mercaptopyruvate sulfur transferase and caspase-3 in rat model of non-alcoholic fatty liver disease

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Abstract

Non-alcoholic fatty liver disease (NAFLD) is the commonest cause of liver morbidity and mortality and has multiple unclear pathogenic mechanisms. Vitamin D deficiency was associated with increased incidence and severity of NAFLD. Increased hepatic expression of 3-mercaptopyruvate sulfur transferase (MPST) and dysregulated hepatocyte apoptosis were involved in NAFLD pathogenesis. We aimed to explore the protective effect of 1,25-Dihydroxycholecalciferol (1,25-(OH)2 D3) against development of NAFLD and the possible underlying mechanisms, regarding hepatic MPST and caspase-3 expression. 60 male adult rats were divided into 4 and 12 week fed groups; each was subdivided into control, high-fat diet (HFD), and HFD + VD. Serum levels of lipid profile parameters, liver enzymes, insulin, glucose, C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and hepatic levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and reactive oxygen species (ROS) were measured. BMI and HOMA-IR were calculated, and liver tissues were processed for histopathological and immunohistochemical studies. The present study found that 1,25-(OH)2 D3 significantly decreased BMI, HOMA-IR, serum levels of glucose, insulin, liver enzymes, lipid profile parameters, CRP, TNF-α, hepatic levels of MDA, ROS, hepatic expression of MPST, TNF-α, 8-hydroxy-2′-deoxyguanosine (8-OHdG), and caspase-3; and significantly increased hepatic TAC in both HFD-fed groups. In conclusion: Administration of 1,25-(OH)2 D3 with HFD abolished the NAFLD changes associated with HFD in 4-week group, and markedly attenuated the changes in 12-week group. The anti-apoptotic effect via decrement of caspase-3 and MPST expression are novel mechanisms suggested to be implicated in the protective effect of 1,25-(OH)2 D3.

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Acknowledgements

Great appreciation to the Image Analysis Unit of the Human Anatomy and Embryology Department, Zagazig University for executing the histopathological and morphometrical studies.

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Authors and Affiliations

  1. Department of Medical Physiology, Faculty of Medicine, Zagazig University, Zagazig, 44519, Egypt

    Maher N. Ibrahim, Abeer A. Khalifa, Dalia A. Hemead & Marwa A. Habib

  2. Department of Human Anatomy and Embryology, Faculty of Medicine, Zagazig University, Zagazig, 44519, Egypt

    Amira Ebrahim Alsemeh

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  1. Maher N. Ibrahim
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  2. Abeer A. Khalifa
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  4. Amira Ebrahim Alsemeh
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Contributions

MAH prepared the design, interpretation of the studies, analysis of the data and wrote the manuscript; MAH and DAH conducted the experiments, AEA performed the histological, and immunohistochemical and morphometrical studies and analyzing them, MNI revised the manuscript, AAK and MAH revised and prepared the manuscript for publications.

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Correspondence to Amira Ebrahim Alsemeh.

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Ibrahim, M.N., Khalifa, A.A., Hemead, D.A. et al. 1,25-Dihydroxycholecalciferol down-regulates 3-mercaptopyruvate sulfur transferase and caspase-3 in rat model of non-alcoholic fatty liver disease. J Mol Histol 54, 119–134 (2023). https://doi.org/10.1007/s10735-023-10118-9

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