Anti-inflammatory and antioxidant activity of essential amino acid α-ketoacid analogues against renal ischemia-reperfusion damage in Wistar rats

Abstract

Introduction: Essential amino acid α-keto acid analogues (EAAs) are used in the treatment of chronic kidney disease (CKD) to delay the symptoms of uremia. However, it is unknown whether EAAs affect oxidative stress and inflammation present in acute renal injury, such as that produced by ischemia-reperfusion (I/R). Objective: The purpose of this study was to evaluate the effect of EAAs on renal I/R injury in Wistar rats. Materials and methods: Rats were divided into 11 groups (n = 6/group): two groups received physiological saline with or without I/R injury (45 min/24 h), six groups received EAAs (400, 800, or 1200 mg/kg/24 h/7d) with or without I/R injury (EAAs+I/R), and two groups received allopurinol (ALO) (50 mg/kg/24 h/7d) with or without I/R injury. Biochemical markers included creatinine and blood urea nitrogen (BUN), proinflammatory cytokines (IL-1β, IL-6, and TNF-α), renal damage markers (cystatin C, KIM-1, and NGAL), and markers of oxidative stress such as malondialdehyde (MDA) and total antioxidant activity (AOxT). Results: The EAAs-and ALO-treated groups had lower levels of creatinine, BUN, renal damage markers, proinflammatory cytokines, and MDA than their corresponding I/R groups; these changes related to the EAAs dosage. AOxT was lower in EAAs-and ALO-treated groups than in corresponding I/R groups. Conclusions: This is the first report of the nephroprotective effects of EAAs against I/R injury. EAAs decreased the levels of biochemical markers, kidney injury markers, proinflammatory cytokines, and MDA while minimizing total antioxidant consumption.