Oxygen Free Radical Induced Damage in Kidneys Subjected to Warm Ischemia and Reperfusion

Abstract

Superoxide anion free radical (O2-.) has been implicated in the pathogenesis of tissue injury consequent to ischemia/reperfusion in several different organs, including heart and bowel. Superoxide dismutase (SOD), an enzyme free radical scavenger specific for O2-., has been used successfully to protect these organs from structural damage during reoxygenation of ischemic tissue. It has been suggested that the catalytic action of xanthine oxidase in injured tissue is an important source of O2-. during reoxygenation. In order to evaluate the potential of SOD to protect against kidney damage resulting from transient ischemia followed by reperfusion with oxygenated blood, a model of warm renal ischemia was studied. LBNF1 rats underwent right nephrectomy and occlusion of the left renal artery for 45 minutes. Survival in the group of ischemic untreated rats (N = 30) was 56% at 7 days and serum creatinine was greatly elevated (p less than 0.01) in rats remaining alive over the full 7-day period. In strong contrast to these results, all of the animals treated with SOD before reperfusion (N = 18) were alive after 7 days similar to sham operated control rats (N = 8). Serum creatinine in the SOD treated rats was significantly elevated only to postoperative day 3 and thereafter returned to normal. Rats treated with inactive SOD (N = 4) or SOD before ischemia (N = 4) had decreased survival rates compared to ischemic untreated animals and prolonged elevation of serum creatinine. When the ischemia time was extended to 60 minutes, only 19% of the untreated animals (N = 16) survived at 7 days whereas nearly 60% of the SOD-treated animals survived (N = 19). Serum creatinine was greatly elevated during the full 7-day observation period in all surviving rats in the untreated ischemic group, whereas serum creatinine returned to normal (p less than 0.05) after 4 days in the surviving rats treated with SOD. To test whether the action of xanthine oxidase contributed to the kidney damage after reoxygenation, 45 min. ischemic rat kidneys were treated with allopurinol. All of the animals treated with allopurinol (N = 12) were alive at 7 days. Serum creatinine values returned to normal after the episode of ischemia and reperfusion but more slowly than after SOD treatment. Histologic evaluation of kidney tissue taken from animals after ischemia alone showed extensive renal tubular damage, which was essentially absent in kidneys from SOD-treated animals.(ABSTRACT TRUNCATED AT 400 WORDS)

Tempol Reduces Oxidative Stress, Improves Insulin Sensitivity, Decreases Renal Dopamine D1 Receptor Hyperphosphorylation, and Restores D1 Receptor–G-Protein Coupling and Function in Obese Zucker Rats

“…One of the novel observations of our study is that 2-week treatment with tempol not only lowered the oxidative stress but also improved the insulin sensitivity and decreased blood pressure. Administration of antioxidant enzymes such as SOD and catalase has been shown to prevent or treat hypertension (31,32). However, the potential benefits of the systemic administration of SOD are limited, because SOD does not permeate biological membranes and is, therefore, unable to remove O 2 Ϫ produced intracellularly.…”

The Role of Carnitine in Preventing Renal Damage Developed as a Result of Infrarenal Aortic Ischemia–Reperfusion

“…In many studies serum and/or tissue MDA levels were shown as increased. 19,20,22,[44][45][46][47] In our study, serum creatinine and tissue MDA levels were significantly higher in AIR group than other groups. Also there was a positive correlation between serum creatinine and tissue MDA levels and between creatinine values and TSHD.…”

Effects of Flaxseed oil supplementation on renal dysfunction due to ischemia/reperfusion in rat

“…Multiple mediators are involved in the pathogenesis of ARFs such as ROSs, cytokines and adhesion molecules/chemokines which activate the leukocytes and endothelial cells that lead to inflammation, tubular damage and endothelial dysfunction (20,21) and paradoxically subsequent blood reflow enhances the damage in the renal tissue (22). By increasing the ROSs as an important factor in the pathogenesis of ARFs in the ischemic environment, the antioxidants reduce and resulting in oxidative stress and tissue impairment (23). In the current study, ischemia reperfusion resulted in increased MDA level as a lipid peroxidation production and decreased SOD level.…”