Alqahtani Qamraa H, Alshehri Samiyah, Alhusaini Ahlam M, Sarawi Wedad S, Alqarni Sana S, Mohamed Raessa, Kumar Meha N, Al-Saab Juman, Hasan Iman H
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia.
Department of Clinical Laboratory Science, College of Applied Medical Sciences, King Saud University, P.O. Box 2925, Riyadh 11461, Saudi Arabia.
Diseases. 2023 Dec 18;11(4):184. doi: 10.3390/diseases11040184.
Diabetes is a ubiquitous disease that causes several complications. It is associated with insulin resistance, which affects the metabolism of proteins, carbohydrates, and fats and triggers liver diseases such as fatty liver disease, steatohepatitis, fibrosis, and cirrhosis. Despite the effectiveness of Sitagliptin (ST) as an antidiabetic drug, its role in diabetes-induced liver injury is yet to be fully investigated. Therefore, this study aims to investigate the effect of ST on hepatic oxidative injury, inflammation, apoptosis, and the mTOR/NF-κB/NLRP3 signaling pathway in streptozotocin (STZ)-induced liver injury. Rats were allocated into four groups: two nondiabetic groups, control rats and ST rats (100 mg/kg), and two diabetic groups induced by STZ, and they received either normal saline or ST for 90 days. Diabetic rats showed significant hyperglycemia, hyperlipidemia, and elevation in liver enzymes. After STZ induction, the results revealed remarkable increases in hepatic oxidative stress, inflammation, and hepatocyte degeneration. In addition, STZ upregulated the immunoreactivity of NF-κB/p65, NLRP3, and mTOR but downregulated IKB-α in liver tissue. The use of ST mitigated metabolic and hepatic changes induced by STZ; it also reduced oxidative stress, inflammation, and hepatocyte degeneration. The normal expression of NF-κB/p65, NLRP3, mTOR, and IKB-α were restored with ST treatment. Based on that, our study revealed for the first time the hepatoprotective effect of ST that is mediated by controlling inflammation, oxidative stress, and mTOR/NF-κB/NLRP3 signaling.
糖尿病是一种普遍存在的疾病，会引发多种并发症。它与胰岛素抵抗相关，胰岛素抵抗会影响蛋白质、碳水化合物和脂肪的代谢，并引发诸如脂肪肝、脂肪性肝炎、纤维化和肝硬化等肝脏疾病。尽管西他列汀（ST）作为一种抗糖尿病药物具有疗效，但其在糖尿病诱发的肝损伤中的作用尚未得到充分研究。因此，本研究旨在探讨ST对链脲佐菌素（STZ）诱导的肝损伤中肝脏氧化损伤、炎症、细胞凋亡以及mTOR/NF-κB/NLRP3信号通路的影响。将大鼠分为四组：两个非糖尿病组，即对照大鼠和ST大鼠（100毫克/千克），以及两个由STZ诱导的糖尿病组，它们分别接受生理盐水或ST治疗90天。糖尿病大鼠表现出显著的高血糖、高血脂以及肝酶升高。在STZ诱导后，结果显示肝脏氧化应激、炎症和肝细胞变性显著增加。此外，STZ上调了肝脏组织中NF-κB/p65、NLRP3和mTOR的免疫反应性，但下调了IKB-α。使用ST减轻了STZ诱导的代谢和肝脏变化；它还降低了氧化应激、炎症和肝细胞变性。ST治疗恢复了NF-κB/p65、NLRP3、mTOR和IKB-α的正常表达。基于此，我们的研究首次揭示了ST通过控制炎症、氧化应激和mTOR/NF-κB/NLRP3信号传导介导的肝脏保护作用。
