Lipoic Acid Prevents Renal Dysfunction in Experimental Diabetes

Abstract

IntroductionDiabetic nephropathy affects approximately 30–40% of patients with type 1 diabetes mellitus and 8% to 10% of patients with type 2 diabetes, and is the main cause of end‐stage renal disease, requiring hemodialysis or renal transplantation.ObjectiveThe study evaluated the effect of lipoic acid for 60 days in the prevention of experimental diabetic nephropathy in diabetic rats. Male Wistar rats were divided into three groups: euglycemic (eugly; n = 12), untreated diabetic (Diab; n = 6), and diabetic treated with lipoic acid (AL) 20mg/kg every 12 hours Orally (Diab + AL; n = 12) for 60 days. The animals were induced to diabetes with intraperitoneal injection of streptozotocin (STZ) (65 mg/kg, i.p), diluted in citrate buffer (pH 4.5). The control group received only citrate buffer (0.1mL/100g; i.p). Renal function was evaluated in metabolic cages on days 0, 15, 30, 45 and 60, with collection of urine and blood. After 60 days, all the animals were assigned to functional studies of renal hemodynamics and pressure natriuresis, in addition to molecular marker studies of diabetic nephropathy.ResultsThe animals studied presented classic diabetes characteristics such as hyperglycemia, maintained throughout the experimental protocol, polyuria, polydipsia and glycosuria, whose treatment with lipoic acid, was able to improve all these alterations. After 60 days, they presented albuminuria, which was attenuated with AL treatment. The excreted fraction of sodium, was increased 4‐fold in the Diab group and was attenuated in the AL‐treated group. The natriuresis increased about 7‐fold in the Eugli group during the period of increased renal perfusion pressure, however, it was impaired by 65% in the control non‐treated diabetic animals. The AL treated group, however, had normal pressure natriuresis. The renal concentration of gluthatione (GSH) decreased by 48% in the diabetic group when compared to the Eugli group, and the AL treatment restored the GSH levels to control values. The lipoperoxidation marker, malondialdehyde, was increased in the Diab group (68%) but was normal in the AL‐treated diabetic group.ConclusionTreatment with lipoic acid is able to prevent the great majority of changes caused during the course of experimental diabetes, and could be an alternative to the composition of a primary prevention treatment in conjunction with metabolic control drugs.Support or Funding InformationFUNCAP, CAPES and CNPqThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.