Hepatorenal protection in renal ischemia/reperfusion by celecoxib and pentoxifylline

Renal ischemia/reperfusion (I/R) is a major clinical problem. Its pathogenesis is multifactorial involving oxidative stress, cytokine overproduction, and inflammatory responses in the kidney and remote organs. This study was performed to evaluate the effects of celecoxib (CEB) and pentoxifylline (PTX) on kidney and liver changes after renal I/R in rats.

Renal ischemia was induced by clamping renal pedicles for 1 h followed by reperfusion for another 1 h. The rats were assigned to five groups: sham control, untreated I/R, CEB + I/R, PTX + I/R, and (CEB + PTX)+I/R. Drug treatment was given for 7 d before I/R. Serum and tissue biochemical and histomorphologic changes were evaluated after reperfusion.

Renal I/R caused changes in kidney and liver histology with a significant reduction in the function of both organs. An increase in tumor necrosis factor-alpha, myeloperoxidase, and malondialdehyde levels with a decrease in glutathione content and superoxide dismutase activity was observed in kidney and liver tissues. Pretreatment with CEB, PTX, or CEB + PTX attenuated all these changes and the extent of improvement was similar in all drug-treated groups.

This study is the first experimental work demonstrating the simultaneous nephroprotective and hepatoprotective effects of CEB and PTX after renal I/R. It seems likely that both drugs protect the kidney and liver by reducing oxidative stress, attenuating tumor necrosis factor-alpha production and inhibiting neutrophil tissue infiltration. No additive protective effects were observed in rats received the combined treatment. Thus, our results may imply a promising therapeutic approach by using CEB or PTX to protect the kidney and liver against the hazardous consequences of renal I/R.