Prevention of renal ischemia/reperfusion‐induced injury in rats by leflunomide

Abstract

Objective: There is increasing evidence to suggest that toxic oxygen radicals play an essential role in the pathogenesis of ischemia/ reperfusion (I/R) injury in the kidney. This study was designed to investigate the effects of leflunomide, an isoxazole derivative and a unique immunomodulatory agent, in I/R-induced renal injury in rats. Methods: Forty female Sprague-Dawley rats were divided equally into four groups: (I) control (only leflunomide 10 mg/kg, intragastrically treated); (II) sham operated (only unilateral nephrectomy); (III) I/R; and (IV) leflunomide (10 mg/kg for two doses prior to experiment) plus I/R groups. In groups III and IV, after unilateral nephrectomy, the rats were subjected to 60 min of left renal pedicle occlusion, followed by 6 h of reperfusion. At the end of the reperfusion period, rats were killed and kidneys and blood were removed. Catalase, myeloperoxidase and xanthine oxidase activities, and malondialdehyde, nitric oxide and protein carbonyl levels were determined in renal tissue. Serum creatinine, blood urea nitrogen and aspartate aminotransferase were measured for the evaluation of renal function. In histopathological examination, renal damage was scored 0-3. Results: Group III animals demonstrated severe deterioration of renal function, renal morphology and a significant renal oxidative stress. Pretreatment of animals with leflunomide markedly attenuated renal dysfunction, morphological alterations, reduced elevated oxidative stress products levels and restored the depleted renal antioxidant enzyme. Conclusion:The findings imply that oxygen radicals play a causal role in I/R-induced renal injury, and leflunomide exerts renoprotective effects probably by the radical scavenging and antioxidant activities with immunomodulatory effect.

The Protective Effects of Ascorbic Acid against Renal Ischemia-Reperfusion Injury in Male Rats

“…[25] Thus, ROS are believed to play a central role in I/R injury in addition to several other diseases, including neoplasia, atherosclerosis, and neurodegenerative diseases. [8] ROS are capable of reacting with proteins, lipids, and nucleic acids leading to the lipid peroxidation of biological membranes, which in turn impacts upon enzymatic processes such as ion pump activity [15,26] . Previous experiments show that various exogenous antioxidant agents such as allopurinol, melatonin, tocopherol, leflunomide, and some flavonoids have the potential to reduce I/R induced-renal injury and help the improvement of kidney function.…”

“…Previous experiments show that various exogenous antioxidant agents such as allopurinol, melatonin, tocopherol, leflunomide, and some flavonoids have the potential to reduce I/R induced-renal injury and help the improvement of kidney function. [10,[13][14][15]26] In this study, we used AA as an exogenous antioxidant. AA is one of the water-soluble vitamins and is well known as a strong antioxidant agent.…”

Effects of melatonin on the serum levels of pro-inflammatory cytokines and tissue injury after renal ischemia reperfusion in rats

“…The sham group received only nephrectomy without occlusion, while no surgery was performed on the control group. 21 Melatonin (Sigma Chemical Co., St. Louis, MO) was dissolved in ethanol and then diluted in saline (0.09% NaCl wt/vol) to give a final alcohol concentration of 1% ethanol. Melatonin injected to the rats 10 mg/kg intraperitoneally prior to ischemia.…”

Coenzyme Q10and its Relation with Oxidant and Antioxidant System Markers in Patients with End-Stage Renal Disease

“…4 Precise mechanisms of increased oxidative stress in patients with renal disease largely remain speculative at this time despite some experimental data showing role of renin-angiotensin system 5 and immune modulation. 6 In patients with ESRD, the balance between reactive oxygen species (ROS) and antioxidant system is deranged in favor of ROS. To date, it has been clearly demonstrated that different markers of oxidative stress such as glyoxal, F 2 -isoprostanes, and malondialdehyde (MDA) are increased in patients with decreased kidney function.…”