Alsharif Khalaf F, Hamad Asmaa A, Alblihd Mohamed A, Ali Fatma Abo Zakaib, Mohammed Sherine Ahmed, Theyab Abdulrahman, Al-Amer Osama M, Almuqati Malik Saad, Almalki Abdulraheem Ali, Albarakati Alaa Jameel A, Alzahrani Khalid J, Albrakati Ashraf, Albarakati Mohammad Hamed, Abass Doaa, Lokman Maha S, Elmahallawy Ehab Kotb
Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia.
High Altitude Research Center, Taif University, Taif, Saudi Arabia.
Front Vet Sci. 2023 Aug 16;10:1214533. doi: 10.3389/fvets.2023.1214533. eCollection 2023.
Diabetes mellitus (DM) is a chronic metabolic disorder. Hepatopathy is one of the serious effects of DM Melatonin (MT) is a potent endogenous antioxidant that can control insulin output. However, little information is available about the potential association between melatonin and hepatic alpha-fetoprotein expression in diabetes.
This study was conducted to assess the influence of MT on diabetes-related hepatic injuries and to determine how β-cells of the pancreas in diabetic rats respond to MT administration.
Forty rats were assigned to four groups at random (ten animals per group). Group I served as a normal control group. Group II was induced with DM, and a single dose of freshly prepared streptozotocin (45 mg/kg body weight) was intraperitoneally injected. In Group III, rats received 10 mg/kg/day of intraperitoneal melatonin (IP MT) intraperitoneally over a period of 4 weeks. In Group IV (DM + MT), following the induction of diabetes, rats received MT (the same as in Group III). Fasting blood sugar, glycosylated hemoglobin (HbA1c), and serum insulin levels were assessed at the end of the experimental period. Serum liver function tests were performed. The pancreas and liver were examined histopathologically and immunohistochemically for insulin and alpha-fetoprotein (AFP) antibodies, respectively.
MT was found to significantly modulate the raised blood glucose, HbA1c, and insulin levels induced by diabetes, as well as the decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, MT attenuated diabetic degenerative changes in the pancreas and the hepatic histological structure, increased the β-cell percentage area, and decreased AFP expression in the liver tissue. It attenuated diabetes-induced hepatic injury by restoring pancreatic β-cells; its antioxidant effect also reduced hepatocyte injury.
Collectively, the present study confirmed the potential benefits of MT in downregulating the increased hepatic alpha-fetoprotein expression and in restoring pancreatic β-cells in a streptozotocin-induced diabetic rat model, suggesting its promising role in the treatment of diabetes.
糖尿病（DM）是一种慢性代谢紊乱疾病。肝病是糖尿病的严重后果之一。褪黑素（MT）是一种强大的内源性抗氧化剂，可控制胰岛素分泌。然而，关于褪黑素与糖尿病患者肝脏甲胎蛋白表达之间的潜在关联，目前所知甚少。
本研究旨在评估MT对糖尿病相关肝损伤的影响，并确定糖尿病大鼠胰腺β细胞对MT给药的反应。
40只大鼠随机分为四组（每组10只动物）。第一组作为正常对照组。第二组诱导糖尿病，腹腔注射单剂量新鲜配制的链脲佐菌素（45mg/kg体重）。第三组大鼠在4周内腹腔注射10mg/kg/天的腹腔内褪黑素（IP MT）。第四组（DM + MT）在诱导糖尿病后，大鼠接受MT（与第三组相同）。在实验期结束时评估空腹血糖、糖化血红蛋白（HbA1c）和血清胰岛素水平。进行血清肝功能测试。分别对胰腺和肝脏进行组织病理学和免疫组织化学检查，以检测胰岛素和甲胎蛋白（AFP）抗体。
发现MT能显著调节糖尿病引起的血糖、HbA1c和胰岛素水平升高，以及丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）降低。此外，MT减轻了胰腺和肝脏组织结构的糖尿病性退行性变化，增加了β细胞百分比面积，并降低了肝组织中AFP的表达。它通过恢复胰腺β细胞减轻了糖尿病诱导的肝损伤；其抗氧化作用也减少了肝细胞损伤。
总体而言，本研究证实了MT在链脲佐菌素诱导的糖尿病大鼠模型中下调肝脏甲胎蛋白表达增加和恢复胰腺β细胞方面的潜在益处，表明其在糖尿病治疗中具有广阔前景。
