Effect of heme oxygenase-1 on renal function in rats with liver cirrhosis

Guo, Shi‐Bin

doi:10.3748/wjg.v17.i3.322

Cited by 19 publications

(27 citation statements)

References 28 publications

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“…Prior to the pharmacokinetic experiments, the animals were fasted for 12 h with water available ad libitum. Biliary cirrhosis with PH was induced via bile duct ligation (BDL) as previously described (12). The surgical procedures were approved by the Animal Care and Use Committee of Dalian Medical University.…”

Section: Methodsmentioning

confidence: 99%

“…Protein concentration was determined according to the Lowry method using bovine serum albumin as a standard. The western blot assay was performed as previously described (12). Total protein (20 µg/ml) was separated by 10% sodium dodecyl sulphate-polyacrylamide gel electrophoresis and transferred to a polyvinylidene difluoride membrane (EMD Millipore, Bedford, MA, USA).…”

Section: Rt-pcrmentioning

confidence: 99%

“…Tissue samples of the upper jejunums were prepared for immunohistochemical analysis as previously described (12). The primary antibodies for P-gp, MRP2 and CYP3A4 were the same as those used in the western blot analysis, and were used at dilutions of 1:58, 1:100 and 1:70, respectively, with incubation at room temperature for 1-2 h. The primary antibody was replaced with phosphate-buffered saline (Beyotime Institute of Biotechnology) to serve as a negative control.…”

Section: Rt-pcrmentioning

confidence: 99%

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Inhibition of P-glycoprotein, multidrug resistance-associated protein 2 and cytochrome P450 3A4 improves the oral absorption of octreotide in rats with portal hypertension

Sun

Duan

Liu

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to increase the intestinal transport of octreotide (OCT) by targeting the first-pass impact to identify a potential method for decreasing portal vein pressure (PVP) using oral OCT. Thus, the bioavailability of intestinally absorbed OCT was evaluated in normal rats and rats with portal hypertension (PH) that had been administered P-glycoprotein/multidrug resistance-associated protein 2/cytochrome P450 3A4 (P-gp/MRP2/CYP3A4) inhibitors. The mRNA and protein expression levels of P-gp, MRP2 and CYP3A4 were evaluated in normal and PH rats with or without OCT and the inhibitors using RT-PCR, western blot and immunohistochemical analyses. The potential effects of the inhibitor administration on PVP were also examined. The results suggest that P-gp, MRP2 and CYP3A4 play important roles in prohibiting the enteral absorption of OCT, particularly under a PH environment. Moreover, inhibitors of P-gp, MRP2 and CYP3A4 decrease the first-pass effects of OCT and effectively reduce PVP under PH conditions. Therefore, the present results suggest P-gp, MRP2 and CYP3A4 are key factors in the intestinal absorption of OCT. The inhibition of P-gp, MRP2 and CYP3A4 can markedly decrease the first-pass effects of OCT, and their use may facilitate the use of orally administered OCT.

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Section: Methodsmentioning

confidence: 99%

Section: Rt-pcrmentioning

confidence: 99%

Section: Rt-pcrmentioning

confidence: 99%

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Inhibition of P-glycoprotein, multidrug resistance-associated protein 2 and cytochrome P450 3A4 improves the oral absorption of octreotide in rats with portal hypertension

Sun

Duan

Liu

et al. 2016

Experimental and Therapeutic Medicine

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“…Brain biopsies are rarely performed in patients with HE due to the temporary nature of the disease and surgery often not being necessary; therefore, the animal experiment provides an appropriate supplement to the cerebral pathology of patients with HE. In addition, we demonstrated that HO-1 is important in a number of organs involved in end-stage liver disease (9,10). Thus, additional research with selective HO inhibitors and their doses is required.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous studies have indicated that HO-1 expression is upregulated in the liver and the HO/CO pathway may regulate cirrhosis induced in rats by bile duct ligation (BDL), as well as its complications, including hepatorenal and hepatopulmonary syndrome (9,10). In addition, the levels of carboxyhemoglobin (COHb) in the arterial blood of hepatitis B virus-related cirrhosis patients with HE were significantly increased compared with healthy individuals (11).…”

Section: Introductionmentioning

confidence: 99%

Role of the heme oxygenase/carbon monoxide pathway in the pathogenesis and prevention of hepatic encephalopathy

Wang

Yin

Duan

et al. 2013

Molecular Medicine Reports

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Abstract. Hepatic encephalopathy (HE) is a severe complication of liver cirrhosis and its pathogenesis has yet to be fully elucidated. Previous studies have demonstrated that heme oxygenase-1 (HO-1) is important in the induction of liver cirrhosis. The present study aimed to investigate the role of HO-1 in the pathogenesis of HE. Rats were divided into 5 treatment groups; sham, bile duct ligation (BDL), HE, zinc protoporphyrin (ZnPP) and cobalt protoporphyrin (CoPP). The levels of HO-1 were examined by western blotting and quantitative real-time PCR (qRT-PCR). Serum levels of carboxyhemoglobin (COHb), ammonia levels in the plasma and brain, brain water content and portal vein pressure (PVP) were also quantified. Aquaporin-4 expression levels were measured by immunohistochemistry and qRT-PCR. The results demonstrated that the levels of HO-1 in the brain and the serum levels of COHb were significantly increased in the HE group compared with the BDL group. Brain water content, PVP and ammonia levels in the plasma and brain were increased in the HE and CoPP groups; however, these were reduced following the treatment with ZnPP. The levels of AQP-4 expression and oxidative stress in the brain were reduced following treatment with ZnPP and increased following treatment with CoPP. In conclusion, following the inhibition of HO-1 expression, treatment with ZnPP improved HE due to reducing the expression levels of AQP-4 and oxidative stress. Therefore, ZnPP treatment may represent a novel therapeutic approach for HE.

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Inflammation and Edema in the Lung and Kidney of Hemorrhagic Shock Rats Are Alleviated by Biliary Tract External Drainage via the Heme Oxygenase-1 Pathway

et al. 2015

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The lung and kidney are two organs that are easily affected by hemorrhagic shock (HS). We investigated roles of biliary tract external drainage (BTED) in inflammation and edema of the lung and kidney in HS and its relationship with the heme oxygenase-1 (HO-1) pathway. Rat models of HS were induced by drawing blood from the femoral artery until a mean arterial pressure (MAP) of 40 ± 5 mmHg was achieved. A MAP of 40 ± 5 mmHg was maintained for 60 min. Thirty-six Sprague-Dawley rats were randomized to the following groups: sham group; HS group; HS + zinc protoporphyrin IX (ZnPP), a specific HO-1 inhibitor, group; HS + BTED group; HS + BTED + ZnPP group; and HS + BTED + bile infusion (BI) group. HO-1 levels, aquaporin-1 levels, and ratios of dry/wet in the lung and kidney increased markedly after BTED, but tumor necrosis factor-α and myeloperoxidase levels in the lung and kidney decreased significantly after BTED under HS conditions. Under the condition that HO-1 was inhibited by ZnPP, all these effects induced by BTED disappeared in the lung and kidney. These results demonstrated that inflammation and edema of the lung and kidney of HS rats are alleviated by BTED via the HO-1 pathway.

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Effect of heme oxygenase-1 on renal function in rats with liver cirrhosis

Abstract: Low HO-1 expression level in kidney is an important factor for experimental HRS.

Cited by 19 publications

References 28 publications

Inhibition of P-glycoprotein, multidrug resistance-associated protein 2 and cytochrome P450 3A4 improves the oral absorption of octreotide in rats with portal hypertension

Inhibition of P-glycoprotein, multidrug resistance-associated protein 2 and cytochrome P450 3A4 improves the oral absorption of octreotide in rats with portal hypertension

Role of the heme oxygenase/carbon monoxide pathway in the pathogenesis and prevention of hepatic encephalopathy

Inflammation and Edema in the Lung and Kidney of Hemorrhagic Shock Rats Are Alleviated by Biliary Tract External Drainage via the Heme Oxygenase-1 Pathway

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