Melatonin, a potent regulator of hemeoxygenase-1, reduces cardiopulmonary bypass-induced renal damage in rats.
Acute renal dysfunction is a frequent complication after cardiac surgery with cardiopulmonary bypass (CPB). This study was designed to evaluate the potential protective effect of melatonin on CPB-induced renal damage in a rat model. Forty male Sprague-Dawley rats were randomly divided into four groups: sham, control (CPB + placebo), low dose of melatonin (CPB + 10 mg/kg melatonin) and high dose of melatonin (CPB + 20 mg/kg melatonin). Blood samples were collected at the beginning, at the end of CPB, and at 0.5, 1, 2, 3, and 24 hr postoperation. Serum creatinine and blood urea nitrogen levels were assayed. Rats were killed 24 hr after surgery, the histologic appearance of the kidney and malondialdehyde (MDA), myeloperoxidase (MPO), catalase (CAT) and superoxide dismutase (SOD) contents were determined. The expression levels of hemeoxygenase-1 (HO-1) protein and gene were determined using western blotting and real-time PCR, respectively. In the control group, CPB surgery significantly increased urea, creatinine levels in serum, MDA and MPO levels in tissues, while decreasing SOD and CAT activities in tissues. Histopathologic findings of the control group confirmed that there was renal impairment by cast formation and tubular necrosis in the tubular epithelium. These changes were markedly reversed in both low dose of melatonin and high dose of melatonin groups. Furthermore, HO-1 gene transcript and protein were significantly upregulated in the kidney tissues after melatonin treatment compared with the placebo treatment. Our findings show that melatonin was effective in preventing CPB-induced renal damage probably through its antioxidant function and upregulation of HO-1.
Wang
Zhongqiu
Z
Department of Cardiothoracic Surgery, Jinling Hospital, Clinical Medicine School of Nanjing University, Nanjing, China.
Zhang
Junwen
J
Liu
Hao
H
Huang
Hairong
H
Wang
Changtian
C
Shen
Yi
Y
Li
Demin
D
Jing
Hua
H