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-alpha 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-alpha. 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.
Ekşioğlu-Demiralp
Emel
E
Marmara University, School of Medicine, Department of Hematology and Immunology, Istanbul, Turkey. demiralp@marmara.edu.tr
Kardaş
E Riza
ER
Ozgül
Seçkin
S
Yağci
Tayfur
T
Bilgin
Hüseyin
H
Sehirli
Ozer
O
Ercan
Feriha
F
Sener
Göksel
G
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D053978:Pentacyclic Triterpenes; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D016897:Respiratory Burst; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D000094062:Betulinic Acid
D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D009195:Peroxidase; D000254:Sodium-Potassium-Exchanging ATPase; D000094062:Betulinic Acid