Effect of heme oxygenase-1 inducer hemin on chronic renal failure rats

2004 ◽  
Vol 24 (3) ◽  
pp. 250-253 ◽  
Author(s):  
Liu Shenwei ◽  
Shi Liming ◽  
Liu Xiaocheng
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1

Induction of heme oxygenase-1 in toxic renal injury: mercuric chloride-induced acute renal failure in rat

1998 ◽  
Vol 94 (1) ◽  
pp. 57-64 ◽  
Author(s):  
Saburo Horikawa ◽  
Koji Ito ◽  
Satoru Ikeda ◽  
Toshikazu Shibata ◽  
Shino Ishizuka ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Heme Oxygenase ◽  
Mercuric Chloride ◽  
Renal Injury ◽  
Heme Oxygenase 1

Contribution of impaired Nrf2-Keap1 pathway to oxidative stress and inflammation in chronic renal failure

2010 ◽  
Vol 298 (3) ◽  
pp. F662-F671 ◽  
Author(s):  
Hyun Ju Kim ◽  
Nosratola D. Vaziri
Keyword(s):  
Oxidative Stress ◽  
Renal Failure ◽  
Chronic Renal Failure ◽  
Glutathione Depletion ◽  
Heme Oxygenase 1 ◽  
Sham Operation ◽  
Gene Products ◽  
Quinone Oxidoreductase ◽  
Nrf2 Activation ◽  
Remnant Kidney

Oxidative stress and inflammation are constant features and major mediators of progression of chronic kidney disease (CKD). Nuclear factor erythroid-2-related factor-2 (Nrf2) confers protection against tissue injury by orchestrating antioxidant and detoxification responses to oxidative and electrophilic stress. While sources of oxidative stress and inflammation in the remnant kidney have been extensively characterized, the effect of CKD on Nrf2 activation and expression of its downstream gene products is unknown and was investigated. Subgroups of male Sprague-Dawley rats were subjected to 5/6 nephrectomy or sham operation and observed for 6 or 12 wk. Kidneys were then harvested, and Nrf2 activity and its downstream target gene products (antioxidant and phase II enzymes) were assessed. In addition, key factors involved in promoting inflammation and oxidative stress were studied. In confirmation of earlier studies, rats with chronic renal failure exhibited increased lipid peroxidation, glutathione depletion, NF-κB activation, mononuclear cell infiltration, and upregulation of monocyte chemoattractant protein-1, NAD(P)H oxidase, cyclooxygenase-2, and 12-lipoxygenase in the remnant kidney pointing to oxidative stress and inflammation. Despite severe oxidative stress and inflammation, remnant kidney tissue Nrf2 activity (nuclear translocation) was mildly reduced at 6 wk and markedly reduced at 12 wk, whereas the Nrf2 repressor Keap1 was upregulated and the products of Nrf2 target genes [catalase, superoxide dismutase, glutathione peroxidase, heme oxygenase-1, NAD(P)H quinone oxidoreductase, and glutamate-cysteine ligase] were reduced or unchanged at 6 wk and significantly diminished at 12 wk. Thus oxidative stress and inflammation in the remnant kidney are compounded by conspicuous impairment of Nrf2 activation and consequent downregulation of the antioxidant enzymes.

Heme oxygenase-1 induction improves ischemic renal failure: role of nitric oxide and peroxynitrite

2007 ◽  
Vol 293 (6) ◽  
pp. H3542-H3549 ◽  
Author(s):  
Miguel G. Salom ◽  
Susana Nieto Cerón ◽  
Francisca Rodriguez ◽  
Bernardo Lopez ◽  
Isabel Hernández ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Renal Failure ◽  
Acute Renal Failure ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Beneficial Effects ◽  
Medullary Blood Flow ◽  
Ischemic Renal Failure ◽  
Oxide Synthase

The present study evaluated the effects of heme oxygenase-1 (HO-1) induction on the changes in renal outer medullary nitric oxide (NO) and peroxynitrite levels during 45-min renal ischemia and 30-min reperfusion in anesthetized rats. Glomerular filtration rate (GFR), outer medullary blood flow (OMBF), HO and nitric oxide synthase (NOS) isoform expression, and renal low-molecular-weight thiols (–SH) were also determined. During ischemia significant increases in NO levels and peroxynitrite signal were observed (from 832.1 ± 129.3 to 2,928.6 ± 502.0 nM and from 3.8 ± 0.7 to 9.0 ± 1.6 nA before and during ischemia, respectively) that dropped to preischemic levels during reperfusion. OMBF and –SH significantly decreased after 30 min of reperfusion. Twenty-four hours later, an acute renal failure was observed (GFR 923.0 ± 66.0 and 253.6 ± 55.3 μl·min−1·g kidney wt−1 in sham-operated and ischemic kidneys, respectively; P < 0.05). The induction of HO-1 (CoCl2 60 mg/kg sc, 24 h before ischemia) decreased basal NO concentration (99.7 ± 41.0 nM), although endothelial and neuronal NOS expression were slightly increased. CoCl2 administration also blunted the ischemic increase in NO and peroxynitrite (maximum values of 1,315.6 ± 445.6 nM and 6.3 ± 0.5 nA, respectively; P < 0.05), preserving postischemic OMBF and GFR (686.4 ± 45.2 μl·min−1·g kidney wt−1). These beneficial effects of CoCl2 on ischemic acute renal failure seem to be due to HO-1 induction, because they were abolished by stannous mesoporphyrin, a HO inhibitor. In conclusion, HO-1 induction has a protective effect on ischemic renal failure that seems to be partially mediated by decreasing the excessive production of NO with the subsequent reduction in peroxynitrite formation observed during ischemia.

Theophylline protects against glycerol-induced acute renal failure: Regulation of heme oxygenase-1 and glutathione in rat kidney

1997 ◽  
Vol 1 (3) ◽  
pp. 204-211 ◽  
Author(s):  
Shino Ishizuka ◽  
Yoji Nagashima ◽  
Masayoshi Sone ◽  
Kiyokazu Hagiwara ◽  
Saburo Horikawa
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Heme Oxygenase ◽  
Rat Kidney ◽  
Heme Oxygenase 1

scholarly journals Exacerbation of Chronic Renovascular Hypertension and Acute Renal Failure in Heme Oxygenase-1–Deficient Mice

2001 ◽  
Vol 88 (10) ◽  
pp. 1088-1094 ◽  
Author(s):  
Philippe Wiesel ◽  
Anand P. Patel ◽  
Irvith M. Carvajal ◽  
Zhi Yuan Wang ◽  
Andrea Pellacani ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Renovascular Hypertension ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Deficient Mice

Role of heme oxygenase-1 in endotoxemic acute renal failure

2005 ◽  
Vol 289 (6) ◽  
pp. F1382-F1385 ◽  
Author(s):  
Brian Poole ◽  
Wei Wang ◽  
Yung-Chang Chen ◽  
Einath Zolty ◽  
Sandor Falk ◽  
...  
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Acute Renal Failure ◽  
Heme Oxygenase ◽  
Cell Injury ◽  
Heme Oxygenase 1 ◽  
Zinc Protoporphyrin ◽  
Renal Protection ◽  
Renal Vasoconstriction

The pathogenesis of septic acute renal failure (ARF) involves systemic vasodilation with compensatory upregulation of vasoconstrictors. This can lead to renal vasoconstriction and ARF. Heme oxygenase (HO) is the rate-limiting step in heme metabolism and produces carbon monoxide (CO) and biliverdin. HO-1 is an inducible form of the enzyme and is expressed in response to cell injury. It was hypothesized in endotoxemia, induction of HO-1 would lead to increased production of the vasodilator CO, lower blood pressure, and decrease renal function. The role of HO-1 was therefore examined in a mouse model of endotoxemia. One group of mice received LPS alone and were compared with mice that received LPS in addition to an inhibitor of HO-1, zinc protoporphyrin (ZnPP). Treatment of mice with LPS resulted in significant increases in the protein expression of HO-1 compared with controls treated with vehicle. Immunohistochemical analysis localized this upregulation to both the proximal and distal tubules as well as the vasculature. Hemodynamic studies were performed during endotoxemia and the mean arterial pressure (MAP) was found to be significantly higher in the HO-1 inhibitor-treated compared with vehicle-treated mice (78 ± 3 vs. 64 ± 2 mmHg, P < 0.01). It was found that the inhibitor group had higher renal blood flows (RBF) also during endotoxemia (1.8 ± 0.2 vs. 0.68 ± 0.1 ml/min, P < 0.01). Furthermore, when renal vascular resistance (RVR) was calculated, there was a significant decrease in RVR in the inhibitor group (43.5 ± 3.4 vs. 95.9 ± 11.3 mmHg·ml−1·min−1, P < 0.01). In concert with the hemodynamic data, glomerular filtration rate (GFR), as measured by inulin clearance, was higher in the HO inhibitor compared with the vehicle controls during endotoxemia (111.5 ± 19.5 vs. 66.0 ± 3.5 μl/min, P < 0.05). In summary, during endotoxemia ARF, inhibiting HO-1 with ZnPP resulted in the protection of renal function. The renal protection was associated with significantly improved systemic hemodynamics, less renal vasoconstriction, and a higher GFR.

Heme oxygenase-1 gene ablation or expression modulates cisplatin-induced renal tubular apoptosis

2000 ◽  
Vol 278 (5) ◽  
pp. F726-F736 ◽  
Author(s):  
Fumie Shiraishi ◽  
Lisa M. Curtis ◽  
Leigh Truong ◽  
Kenneth Poss ◽  
Gary A. Visner ◽  
...  
Keyword(s):  
Renal Failure ◽  
Heme Oxygenase ◽  
Renal Injury ◽  
Heme Oxygenase 1 ◽  
Severe Renal Failure ◽  
Gene Ablation ◽  
Renal Tubular ◽  
Induced Apoptosis ◽  
Apoptosis And Necrosis

Heme oxygenase-1 (HO-1) is a 32-kDa microsomal enzyme that catalyzes the conversion of heme to biliverdin, releasing iron and carbon monoxide. Induction of HO-1 occurs as a protective response in cells/tissues exposed to a wide variety of oxidant stimuli. The chemotherapeutic effects of cis-diamminedichloroplatinum(II) (cisplatin), a commonly used anticancer drug, are limited by significant nephrotoxicity, which is characterized by varying degrees of renal tubular apoptosis and necrosis. The purpose of this study was to evaluate the functional significance of HO-1 expression in cisplatin-induced renal injury. Our studies demonstrate that transgenic mice deficient in HO-1 (−/−), develop more severe renal failure and have significantly greater renal injury compared with wild-type (+/+) mice treated with cisplatin. In vitro studies in human renal proximal tubule cells demonstrate that hemin, an inducer of HO-1, significantly attenuated cisplatin-induced apoptosis and necrosis, whereas inhibition of HO-1 enzyme activity reversed the cytoprotective effect. Overexpression of HO-1 resulted in a significant reduction in cisplatin-induced cytotoxicity. These studies provide a basis for future studies using targeted gene expression of HO-1 as a therapeutic and preventive modality in high-risk settings of acute renal failure.

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