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Naderi, Roya, Shirpoor, Alireza, Samadi, Mahrokh, Gholizadeh-Ghaleh Aziz, Shiva. (1403). Transcriptional factors of FAT/CD36, PTP1B, SREBP-1c and HNF4A are involved in dyslipidemia following Cyclosporine A treatment in the liver of male rats: The protective effect of curcumin. سامانه مدیریت نشریات علمی, 80(1), 233-241. doi: 10.32592/ARI.2025.80.1.233
Roya Naderi; Alireza Shirpoor; Mahrokh Samadi; Shiva Gholizadeh-Ghaleh Aziz. "Transcriptional factors of FAT/CD36, PTP1B, SREBP-1c and HNF4A are involved in dyslipidemia following Cyclosporine A treatment in the liver of male rats: The protective effect of curcumin". سامانه مدیریت نشریات علمی, 80, 1, 1403, 233-241. doi: 10.32592/ARI.2025.80.1.233
Naderi, Roya, Shirpoor, Alireza, Samadi, Mahrokh, Gholizadeh-Ghaleh Aziz, Shiva. (1403). 'Transcriptional factors of FAT/CD36, PTP1B, SREBP-1c and HNF4A are involved in dyslipidemia following Cyclosporine A treatment in the liver of male rats: The protective effect of curcumin', سامانه مدیریت نشریات علمی, 80(1), pp. 233-241. doi: 10.32592/ARI.2025.80.1.233
Naderi, Roya, Shirpoor, Alireza, Samadi, Mahrokh, Gholizadeh-Ghaleh Aziz, Shiva. Transcriptional factors of FAT/CD36, PTP1B, SREBP-1c and HNF4A are involved in dyslipidemia following Cyclosporine A treatment in the liver of male rats: The protective effect of curcumin. سامانه مدیریت نشریات علمی, 1403; 80(1): 233-241. doi: 10.32592/ARI.2025.80.1.233

Transcriptional factors of FAT/CD36, PTP1B, SREBP-1c and HNF4A are involved in dyslipidemia following Cyclosporine A treatment in the liver of male rats: The protective effect of curcumin

Archives of Razi Institute
مقاله 29، دوره 80، شماره 1، فروردین و اردیبهشت 2025، صفحه 233-241    اصل مقاله (579.67 K)
نوع مقاله: Original Articles
شناسه دیجیتال (DOI): 10.32592/ARI.2025.80.1.233
نویسندگان
Roya Naderi* ؛ Alireza Shirpoor؛ Mahrokh Samadi؛ Shiva Gholizadeh-Ghaleh Aziz
Urmia University of Medical Sciences, Urmia, Iran
چکیده
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 30 mg/kg and curcumin at 40 mg/kg via a gastric tube for a duration of 28 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 1B (PTP1B), Fatty acid translocase CD36 (FAT/CD36), sterol regulatory element-binding protein-1c (SREBP-1c) and a significant decrease in hepatocyte nuclear factor 4 Alpha (HNF4A) 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/CD36, PTP1B and HNF4A 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.
کلیدواژه‌ها
Cyclosporine A؛ liver؛ curcumin؛ fibrosis؛ FAT/CD36
عنوان مقاله [English]
فاکتورهای رونویسی FAT/CD36، PTP1B، SREBP-1c و HNF4A در دیس لیپیدمی به دنبال درمان سیکلوسپورین A در کبد موش های صحرایی نر: اثر محافظتی کورکومین
چکیده [English]
سیکلوسپورین A (CsA) به عنوان یک داروی سرکوب کننده سیستم ایمنی قوی، گزارش شده است که باعث اختلالات مختلف از جمله سمیت کبدی می شود. با این حال، میانجی های مولکولی درگیر در آسیب کبدی ناشی از CsA بطور کامل مشخص نشده است. این مطالعه به دنبال توصیف عوامل رونویسی متابولیسم لیپید در آسیب کبدی ناشی از CsA به تنهایی یا در ترکیب با کورکومین بود. در مجموع بیست و هشت موش صحرایی نر ویستار به چهار گروه کنترل (Con)، شم، سیکلوسپورین A (CsA)، سیکلوسپورینA + کورکومین (CsA+cur) تقسیم شدند. موش‌ها سیکلوسپورین A (30 میلی‌گرم بر کیلوگرم) و کورکومین (40 میلی‌گرم بر کیلوگرم) را به مدت 28 روز از طریق گاواژ دریافت کردند. RT-PCR ورنگ آمیزی تری کروم ماسون جهت بررسی تغییرات استفاده شدند. نتایج نشان داد که قرار گرفتن در معرض CsA باعث افزایش قابل توجهی در ژن های 1B (PTP1B)، CD36 (FAT/CD36)، (SREBP-1c) و کاهش قابل توجهی در بیان ژن (HNF4A) در مقایسه با گروه کنترل و شم گردید. تجویز CsA همچنین LDL پلاسما، کلسترول، تری گلیسیرید، آلانین آمینوترانسفراز (ALT) آسپارتات آمینوترانسفراز (AST) و آلکالین فسفاتاز (ALP) را در مقایسه با گروه شاهد و شم به طور قابل توجهی افزایش داد. تغییرات فیبروتیک در گروه CsA با رنگ آمیزی تری کروم ماسون مشاهده شد. مصرف کورکومین منجر به بهبود قابل توجهی در تغییرات بافت شناسی و میانجی های مولکولی درگیر در آسیب کبد بدنبال CsA شد. در مجموع، یافته‌های ما پیشنهاد می‌کند که CsA می‌تواند از طریق اختلالات هموستاز لیپیدی به واسطه تغییرات بیان ژن FAT/CD36، PTP1B و HNF4A به بافت کبد آسیب برساند. همچنین نشان می دهد که این اثرات منفی CsA را می توان با استفاده از کورکومین به عنوان یک آنتی اکسیدان و عامل ضد التهاب کاهش داد.
کلیدواژه‌ها [English]
سیکلوسپورین A, کبد, کورکومین, فیبروز, FAT/CD36
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