Dugbartey George J, Alornyo Karl K, N'guessan Benoit B, Atule Stephen, Mensah Samuel D, Adjei Samuel
Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.
Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.
Biomed Pharmacother. 2022 May;149:112818. doi: 10.1016/j.biopha.2022.112818. Epub 2022 Mar 11.
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Current pharmacological interventions only retard DN progression. Alpha-lipoic acid (ALA) is a potent antioxidant with beneficial effect in other diabetic complications. This study investigates whether ALA supplementation prevents early development and progression of DN.
Fifty-eight male Sprague-Dawley rats were randomly assigned to healthy control and diabetic groups and subjected to overnight fasting. Type 2 diabetes mellitus (T2DM) was induced in diabetic group by intraperitoneal administration of nicotinamide (110 mg/kg) and streptozotocin (55 mg/kg). On day 3 after T2DM induction, diabetic rats received oral daily administration of ALA (60 mg/kg), gliclazide (15 mg/kg), ramipril (10 mg/kg) or drug combinations for 6 weeks. Untreated diabetic rats served as diabetic control. Blood, kidneys and pancreas were harvested for biochemical and histological analyses.
Induction of T2DM resulted in hypoinsulinemia, hyperglycemia and renal pathology. ALA supplementation maintained β-cell function, normoinsulinemia and normoglycemia in diabetic rats, and prevented renal pathology (PAS, KIM-1, plasma creatinine, total protein, blood urea nitrogen, uric acid and urine albumin/creatinine ratio) and triglycerides level compared to diabetic control (p < 0.001). Additionally, ALA supplementation significantly prevented elevated serum and tissue malondialdehyde, collagen deposition, α-SMA expression, apoptosis and serum IL-1β and IL-6 levels while it markedly increased renal glutathione content and plasma HDL-C compared to diabetic control group (p < 0.001).
ALA supplementation prevents early development and progression of DN by exerting anti-hyperglycemic, antioxidant, anti-inflammatory, anti-fibrotic and anti-apoptotic effects. Our findings provide additional option for clinical treatment of DN in T2DM patients.
糖尿病肾病（DN）是终末期肾病的主要病因。目前的药物干预只能延缓DN的进展。α-硫辛酸（ALA）是一种有效的抗氧化剂，对其他糖尿病并发症具有有益作用。本研究调查补充ALA是否能预防DN的早期发生和进展。
58只雄性Sprague-Dawley大鼠随机分为健康对照组和糖尿病组，并进行过夜禁食。糖尿病组通过腹腔注射烟酰胺（110mg/kg）和链脲佐菌素（55mg/kg）诱导2型糖尿病（T2DM）。在诱导T2DM后第3天，糖尿病大鼠每日口服ALA（60mg/kg）、格列齐特（15mg/kg）、雷米普利（10mg/kg）或药物组合，持续6周。未治疗的糖尿病大鼠作为糖尿病对照组。采集血液、肾脏和胰腺进行生化和组织学分析。
T2DM的诱导导致低胰岛素血症、高血糖和肾脏病变。与糖尿病对照组相比，补充ALA可维持糖尿病大鼠的β细胞功能、正常胰岛素血症和正常血糖，并预防肾脏病变（PAS、KIM-1、血浆肌酐、总蛋白、血尿素氮、尿酸和尿白蛋白/肌酐比值）和甘油三酯水平（p<0.001）。此外，与糖尿病对照组相比，补充ALA可显著预防血清和组织丙二醛升高、胶原蛋白沉积、α-SMA表达、细胞凋亡以及血清IL-1β和IL-6水平升高，同时显著增加肾脏谷胱甘肽含量和血浆HDL-C（p<0.001）。
补充ALA通过发挥抗高血糖、抗氧化、抗炎、抗纤维化和抗凋亡作用，预防DN的早期发生和进展。我们的研究结果为T2DM患者DN的临床治疗提供了额外的选择。
