Betulinic acid protects against ischemia/reperfusion‐induced renal damage and inhibits leukocyte apoptosis

The possible protective effect of betulinic acid on renal ischemia/reperfusion (I/R) injury was studied. Wistar Albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 6 h of reperfusion. Betulinic acid (250 mg/kg, i.p.) or saline was administered at 30 min prior to ischemia and immediately before the reperfusion. Creatinine, blood urea nitrogen (BUN), lactate dehydrogenase (LDH) and TNF‐α as well as the oxidative burst of neutrophil and leukocyte apoptosis were assayed in blood samples. Malondialdehyde (MDA), glutathione (GSH) levels, Na⁺, K⁺‐ATPase and myeloperoxidase (MPO) activities were determined in kidney tissue which was also analysed microscopically. I/R caused significant increases in blood creatinine, BUN, LDH and TNF‐α. In the kidney samples of the I/R group, MDA levels and MPO activity were increased significantly, however, GSH levels and Na⁺, K⁺‐ATPase activity were decreased. Betulinic acid ameliorated the oxidative burst response to both formyl‐methionyl‐leucyl‐phenylalanine (fMLP) and phorbol 12‐myristate 13‐acetate (PMA) stimuli, normalized the apoptotic response and most of the biochemical indices as well as histopathological alterations induced by I/R. In conclusion, these data suggest that betulinic acid attenuates I/R‐induced oxidant responses, improved microscopic damage and renal function by regulating the apoptotic function of leukocytes and inhibiting neutrophil infiltration. Copyright © 2009 John Wiley & Sons, Ltd.