Role of Oxygen Free Radical Scavengers in Acute Renal Failure Complicating Obstructive Jaundice

Abstract

Obstructive jaundice is associated with high morbidity and mortality. Major complications such as pulmonary dysfunction, renal failure and sepsis are frequently encountered. Recent studies and observations suggest that the free oxygen radicals (FORs) produced in obstructive jaundice may play a significant role in the etiopathogenesis of acute renal failure (ARF). Thirty rats were divided into three groups, as sham, control and treatment groups containing 10 rats each. Laparatomy was performed on each animal in the control and treatment groups and common bile ducts were ligated. Common bile duct was observed but was not ligated for the rats in the sham group. Saline solution injection was begun on the first day of surgical procedure and repeated once a day during the following 5 days. The same procedure was performed with oxygen radical scavenger dimethyl sulfoxide (1.5 mg/kg/day i.p.) instead of saline in the treatment group. The rats were sacrificed on the 7th postoperative day. On the 7th postoperative day, the bilirubin, urea and creatinine levels of the control and treatment groups were significantly higher in comparison with the sham group (p < 0.01). Although there was no statistically significant difference between the bilirubin levels of the control and treatment groups (p > 0.05), the urea and creatinine levels in the treatment group were significantly lower (p < 0.01). On the 7th postoperative day, the erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels of the control and treatment groups were significantly lower than those of the sham group (p < 0.01), whereas renal and erythrocyte malondialdehyde (MDA) levels were significantly higher (p < 0.01). Although SOD and GSH-Px levels did not differ significantly between the treatment and control groups (p > 0.05), renal and erythrocyte MDA levels of the treatment group were significantly lower than those of the control group (p < 0.01). The histopathological scores were significantly higher in the control and treatment groups (p < 0.01); there was no significant difference between the control and treatment groups (p > 0.05). FORs seem to play a significant role in the etiopathogenesis of renal failure in obstructive jaundice. Antioxidant treatment may decrease oxidative damage due to FORs and may prevent renal failure.

Preventing oxygen free radical damage by proanthocyanidin in obstructive jaundice

“…We observed a significant decrease in pulmonary neutrophil leukocyte infiltration in the treatment group in comparison to the control group (p<0.05). Although the etiology of renal function disorders in obstructive jaundice is yet to be known, it has been suggested that cellular and extracellular hypovolemia, increase in oxygen free radicals, and decrease in antioxidant functions play a significant role (26,27). While there was a decrease in the scope of renal tubule damage in the treatment group of our study, it was not statistically significant.…”

Alteration of the renal regulatory hormonal pattern during experimental obstructive jaundice

“…The depletion of the extracellular compartment (4), myocardial dysfunction, and altered hemodynamic status (5) have been linked to renal failure in biliary obstruction. In addition, severe oxidative stress has been implicated in the renal dysfunction associated to experimental OJ (6,7) as well as other liver diseases (8). Other lines of research have looked at the involvement of vasoactive mediators such as endothelin-1 (ET-1).…”

Cholestasis induced nephrotoxicity: The role of endogenous opioids

“…Renal failure is one of the most frequent complications of obstructive jaundice and acute renal failure is observed in 4-18% of the patients (Kucuk et al 2003). Similarly, acute renal injury secondary to intra or extrahepatic bile duct obstruction is one of the main causes of postoperative multiple system failure, which affects approximately 6%-8% of patients with over 68% mortality (Fogarty et al 1995;Holt et al 1999).…”

“…This can be related to significant biochemical and metabolic changes that mightplay an independent role in contributing to the development of renal failure. These biochemical alterations include accumulation of bile acids and billirubin, increased levels of free oxygen radicals, endogenous opioids, and endotoxemia (Green and Better 1995;Kucuk et al 2003). The role of bile constituents (e.g., bile acids, bilirubin, cholesterol) is still controversial in mediating renal damage, but the role of plasma endogenous opioids, mainly methionine enkephalin, is extensively investigated and confirmed in terms of the pathophysiology of cholestatic disease and its complications (Dehpour et al 1998;Ghaffari et al 2004;Swain et al 1992).…”