Transcriptional Factors of FAT/CD36, PTP1B, SREBP-1c and HNF4A Are Involved in Dyslipidemia Following Cyclosporine a Treatment in the Liver of Rats: The Rescue Effect of Curcumin.
A Shirpoor, M Samadi, S Gholizadeh-Ghaleh Aziz, R Naderi
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引用次数: 0
Abstract
Cyclosporine A (CsA) is a potent immunosuppressive agent that has been reported to cause various disorders, including hepatotoxicity. However, the precise molecular mediators involved in CsA-induced liver injury remain to be fully elucidated. The present study aspires to elucidate the transcription factors implicated in lipid metabolism in the context of hepatic injury induced by cyclosporine A (CsA), both independently and in conjunction with curcumin. A total of twenty-eight male adult Wistar rats were assigned into four groups, including control (Con), sham, cyclosporine A (CsA), and cyclosporine A (CsA) + curcumin (CsA+cur). The rats were administered CsA at a dosage of 30 mg/kg and curcumin at 40 mg/kg via a gastric tube for a duration of 28 days. RT-PCR and Masson trichrome staining were used to measure related changes. The results demonstrated that CsA exposure led to a substantial upregulation of protein tyrosine phosphatase 1B (PTP1B), fatty acid translocase CD36 (FAT/CD36), and sterol regulatory element-binding protein-1c (SREBP-1c) genes, along with a notable decrease in hepatocyte nuclear factor 4 Alpha (HNF4A) gene expression compared to the control and sham groups. Furthermore, CsA treatment led to a substantial elevation in plasma lipids (LDL, cholesterol, triglycerides) and liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP)), in comparison to the control and sham groups. Furthermore, fibrotic changes were detected in the CsA group through Masson trichrome staining. Curcumin consumption resulted in a considerable improvement in histological disorders and molecular mediators involved in liver injury following CsA treatment. Consequently, these findings collectively suggest that CsA can exert deleterious effects on liver tissue, manifesting as lipid homeostasis disorders, as evidenced by alterations in FAT/CD36, PTP1B, and HNF4A gene expression. The findings of this study suggest that the use of curcumin, a natural antioxidant and anti-inflammatory agent, can mitigate the adverse effects of CsA on liver tissue by restoring lipid homeostasis.