Transcriptional factors of FAT/CD۳۶, PTP۱B, SREBP-۱c and HNF۴A are involved in dyslipidemia following Cyclosporine A treatment in the liver of male rats: The protective effect of curcumin

Cyclosporine A (CsA) is a potent immunosuppressive drug which has been reported to cause various disorders including hepatotoxicity. However, the precise molecular mediators participated in CsA-induced liver injury remains poorly understood. This study aimed to characterize the transcription factors involved 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 cyclosporineA +curcumin (CsA+cur). The rats were administered CsA at a dosage of ۳۰ mg/kg and curcumin at ۴۰ mg/kg via a gastric tube for a duration of ۲۸ days. RT-PCR and also Masson trichrome staining were employed to measure related changes. Finally, CsA exposure caused a significant increase in protein tyrosine phosphatase ۱B (PTP۱B), Fatty acid translocase CD۳۶ (FAT/CD۳۶), sterol regulatory element-binding protein-۱c (SREBP-۱c) and a significant decrease in hepatocyte nuclear factor ۴ Alpha (HNF۴A) genes expressions compared to the control and sham group. The CsA treatment also significantly elevated plasma lipids (LDL, cholesterol, triglyceride) and liver enzymes (alanine aminotransferase (ALT) aspartate aminotransferase (AST), alkaline phosphatase (ALP)), compared to the control and sham group. Fibrotic changes were detected in CsA group by Masson trichrome staining. Curcumin consumption resulted in a considerable improvement in histological disorders and molecular mediators involved in liver injury following CsA treatment. Taken together, these findings proposed that CsA can cause deleterious effect to liver tissue via lipid homeostasis disorders mediated by FAT/CD۳۶, PTP۱B and HNF۴A gene expression alterations. It also reveals that these negative effects of CsA can be mitigated by using curcumin as an antioxidant and anti-inflammatory supplement.

کلیدواژه ها:

Cyclosporine A ، liver ، Curcumin ، Fibrosis ، FAT/CD۳۶