Superior protective effects of febuxostat plus alpha-lipoic acid on renal ischemia/reperfusion-induced hepatorenal injury in rats

• Main Authors: Mahmoud M Farag, Sally M Ahmed, Wessam F Elhadidy, Radwa M Rashad
• Format: Article
• Language: English
• Published: Wolters Kluwer Medknow Publications 2019-01-01
• Series: Saudi Journal of Kidney Diseases and Transplantation
• Online Access: http://www.sjkdt.org/article.asp?issn=1319-2442;year=2019;volume=30;issue=6;spage=1364;epage=1374;aulast=Farag

A complex cascade of pathological events including oxidative stress and inflammation is involved in ischemia/reperfusion (I/R)-induced local and remote organ injuries. This study was performed to evaluate the effects of febuxostat (FEB), a selective xanthine oxidase (XO) inhibitor, and alpha-lipoic acid (ALA), a strong antioxidant, on the kidney and liver changes induced by renal I/R in rats. Renal I/R was induced in rats by clamping renal pedicles for 1 h followed by 2 h reperfusion. Fifty rats were assigned to five groups as follows: sham operated; vehicle + I/R; FEB + I/R; ALA + I/R, and (FEB + ALA) + I/R. Drug treatment was given 24 h and 1 h before I/R induction. Serum and tissue biochemical parameters and histopathological changes were examined after reperfusion. Serum creatinine, urea and uric acid levels, and alanine aminotransferase and aspartate aminotransferase activities were elevated after renal I/R. An increase in XO, myeloperoxidase, and malondialdehyde levels was observed in kidney and liver tissues with a concomitant decrease in both the glutathione level and superoxide dismutase activity. In addition, kidney and liver sections of vehicle-pretreated rats subjected to I/R exhibited a pronounced alteration in microanatomy. FEB, ALA, or FEB + ALA pretreatment attenuated the serum and tissue biochemical changes with amelioration of the histopathological changes in both the kidney and liver. The findings of this study revealed that FEB in combination with ALA had a greater protective effect than either drug alone. Thus, FEB and ALA co-administration may provide a potential superior therapeutic strategy to protect the kidney and liver against renal I/R-induced injury.