Decreased renal heme oxygenase-1 expression contributes to decreased renal function during cirrhosis

Abstract

Heme oxygenase (HO) is the rate-limiting enzyme in the degradation of heme, catalyzing the oxidative cleavage of heme molecules to biliverdin, carbon monoxide, and iron. The present study was designed to investigate the role of HO-1 in the pathogenesis of renal dysfunction during cirrhosis. Biliary cirrhosis was induced in rats by common bile duct ligation (CBDL). Animals were studied 2 and 5 wk after surgery. In kidney from CBDL rats, HO-1 protein expression increased slightly at 2 wk but was abolished at 5 wk. In addition, we confirmed histologically that HO-1 expression was suppressed in renal tubules and interlobular arterioles in 5-wk-old CBDL rats. Conversely, HO-1 expression in liver was strongly increased. Consistent with the development of cirrhosis and renal dysfunction mean arterial pressure (MAP), glomerular filtration rate (GFR), and renal blood flow (RBF) were decreased in CBDL rats compared with sham-operated controls. In sham rats, treatment with the selective HO inhibitor zinc protoporphyrin markedly decreased GFR and RBF to values similar to those measured in CBDL rats without decreasing MAP. In conclusion, decreased renal HO-1 expression contributes to deteriorated renal function and hemodynamics during cirrhosis. This finding provides a novel mechanism for the pathophysiology of renal dysfunction during cirrhosis.

Natural heme oxygenase-1 inducers in hepatobiliary function

“…In kidneys from CBDL rats, Miyazono et al [73] have shown that HO-1 protein expression is increased slightly at 2 wk but is abolished at 5 wk. In addition, histologically, HO-1 expression was suppressed in renal tubules and interlobular arterioles in 5-wk-old CBDL rats.…”

“…Renal HO-1 expression is decreased in cirrhotic rats (bile ligation) in renal tubules and interlobular arterioles, while it is increased in the liver. The decreased HO-1 is related to renal dysfunction [73] . During HPS caused by liver cirrhosis, pulmonary endothelial NOS expression and NO production are increased.…”

Role of Heme Oxygenase-1 in Polymyxin B-Induced Nephrotoxicity in Rats

“…Rats weighing 286 Ϯ 12 g were divided into the following six groups: (i) saline group (control group), rats receiving 3 ml/kg 0.9% NaCl, intraperitoneally (i.p. ), once a day for 5 days; (ii) hemin group, rats receiving 10 mg/kg hemin (11), i.p., once a day for 5 days; (iii) ZnPP group, rats receiving 50 mol/kg zinc protoporphyrin (27), i.p., on day 5; (iv) PMB group, rats receiving 4 mg/kg PMB (10), i.p., once a day for 5 days; (v) PMB plus hemin group, rats receiving 4 mg/kg PMB, i.p., plus 10 mg/kg hemin, i.p., once a day for 5 days; and (vi) PMB plus ZnPP group, rats receiving 4 mg/kg PMB, i.p., once a day for 5 days, plus 50 mol/kg ZnPP, i.p., administered before PMB on day five.…”

Heat Shock Proteins and Mitogen-activated Protein Kinases in Steatotic Livers Undergoing Ischemia-Reperfusion: Some Answers

“…23 Under our conditions, control experiments indicated that the effective dose of ZnPP (which inhibited HO-1) was 20 mg/kg. Although the exact half-life in the circulation of ZnPP is unknown, 58 the plasma ZnPP concentration remained elevated for 2-3 days after a single dose of 25 mg/kg i.p. 59 In regards to SB203580, the elimination half-life of this drug (2.1 mg/kg i.v.)…”