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 analogs are used in the treatment of chronic kidney disease to delay the symptoms of uremia. However, it is unknown whether essential amino acid α-keto acid analogs affect the oxidative stress and the inflammation in acute renal injury such as those produced by ischemia-reperfusion.Objective: To evaluate the effect of essential amino acid α-keto acid analogs on renal ischemia-reperfusion injury in Wistar rats.Materials and methods: Rats were divided into 11 groups (n=6/group): Two groups received physiological saline with or without ischemia-reperfusion injury (45 min/24 h), six groups received essential amino acid α-keto acid analogs (400, 800, or 1,200 mg/kg/24 h/7d) with or without ischemia-reperfusion injury (essential amino acid α-keto acid analogs + ischemia-reperfusion), and two groups received allopurinol (50 mg/kg/24 h/7d) with or without ischemia-reperfusion 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.Results: The essential amino acid α-keto acid analog- and allopurinol-treated groups had lower levels of creatinine, BUN, renal damage markers, proinflammatory cytokines, and MDA than their corresponding ischemia-reperfusion groups. These changes were related to the essential amino acid α-keto acid analogs dosage. Total antioxidant activity was lower in essential amino acid α-keto acid analog- and allopurinol-treated groups than in the corresponding ischemia-reperfusion groups.Conclusions: This is a new report on the nephroprotective effects of essential amino acid α-keto acid analogs against ischemia-reperfusion injury. Essential amino acid α-keto acid analogs decreased the levels of biochemical markers, kidney injury markers, proinflammatory cytokines, and MDA while minimizing total antioxidant consumption.

Thymoquinone and Oleuropein Combination Ameliorates Renal Ischemia-Reperfusion Injury by Attenuating Oxidative Stress in Rats

“…4b). These outcomes were following the previous reports [58][59][60][61] and further substantiate the renal injury caused by the IR surgery. Moreover, a graded pattern of morphological mutilation was seen in the pretreatment groups, which again indicates that TQ and OP have potent nephroprotective potential.…”

Klotho plays a role in reno protective effect of allopurinol on renal ischemia-reperfusion injury

“…Clinical and experimental studies have con rmed the reno-protective effects of klotho(18) and allopurinol (19) in renal dysfunction induced by renal ischemia-reperfusion. Allopurinol, as a xanthine oxidase inhibitor, plays an important role in reducing oxidative stress in ischemic reperfusion (20).…”

Therapeutic Targets for Regulating Oxidative Damage Induced by Ischemia-Reperfusion Injury: A Study from a Pharmacological Perspective

“…These complexes promote the blocking of mitochondrial respiration and membrane disruption during diseases. Further, they are considered the primary cause of cell death in myocardial infarction I-R [ 93 – 95 ]. The mitochondrial antioxidant manganese SOD (MnSOD) expression is one of the objectives for modulating its dismutase scavenging function in superoxide radical O 2 affecting several cell compartments.…”