Three-day tetrahydrobiopterin therapy increases in vivo hepatic NOS activity and reduces portal pressure in CCl4 cirrhotic rats

Matei, Vasilica; Rodríguez–Vilarrupla, Aina; Deulofeu, R.; García‐Calderó, Héctor; Fernández, Mercedes; Bosch, Jaime; García-Pagán, J.C.

doi:10.1016/j.jhep.2008.04.014

Cited by 45 publications

(25 citation statements)

References 29 publications

(38 reference statements)

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“…Trichloromethyl free radicals, produced from CCl 4 metabolism, combine with cellular lipids and proteins in the presence of oxygen forming trichloromethyl peroxyl radicals which attack lipids in the membrane of endoplasmic reticulum faster than trichloromethyl free radical. Thus, trichloromethyl peroxyl free radical elicit lipid peroxidation and destruct Ca 2+ homeostasis, resulting in cell death (Matei et al, 2008). ROS provoke peroxidation of native membrane lipids, leading to altered membrane functions through decreasing its fluidity and changing the activity of its bounding enzymes and their receptors.…”

Section: Discussionmentioning

confidence: 99%

Hesperidin protects against diethylnitrosamine/carbon tetrachloride-induced renal repercussions via up-regulation of Nrf2/HO-1 signaling and attenuation of oxidative stress

2017

J App Pharm Sci

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The kidney plays a central role in detoxification and excretion of toxic metabolites, and therefore is susceptible to toxicity by xenobiotics. Hesperidin is a citrus flavonoid with multiple beneficial therapeutic effects. Here, we investigated the possible modulatory effect of hesperidin on diethylnitrosamine (DEN)/carbon tetrachloride (CCl4)-induced nephrotoxicity in rats, pointing to the role of Nrf2/HO-1 signaling. Male Wistar rats received a single intraperitoneal injection of DEN. Two-weeks later, the DEN-induced rats received a subcutaneous injection of 3 ml/kg CCl4 once/week for 16 weeks. DEN/CCl4-induced rats were treated with 50 and 100 mg/kg hesperidin throughout the experiment. After 18 weeks, DEN/CCl4-induced rats showed renal injury evidenced by the significant increase in circulating kidney function markers as well as histopathological alterations. Concurrent supplementation of hesperidin significantly ameliorated kidney function markers and prevented renal tissue damage induced by DEN/CCl4. In addition, hesperidin treatment suppressed collagen deposition, lipid peroxidation and nitric oxide, and enhanced the antioxidant defenses in the kidney of DEN/CCl4-induced rats. Hesperidin up-regulated the expression of Nrf2 and HO-1 in the kidney of DEN/CCl4-induced rats. In conclusion, hesperidin prevents DEN/CCl4-induced nephrotoxicity via attenuation of oxidative stress and alleviation of the antioxidant defense system. These effects are mediated via up-regulation of Nrf2/ARE/HO-1 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Hesperidin protects against diethylnitrosamine/carbon tetrachloride-induced renal repercussions via up-regulation of Nrf2/HO-1 signaling and attenuation of oxidative stress

2017

J App Pharm Sci

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“…Statins acts in endothelium phenotype improving its properties and resulting in antioxidative, antiproliferative, antiinflammatory and antithrombotic effects [5]. Anti-oxidative stress molecules are found lacking in hepatic cirrhosis [1] as like the tetrahydrobiopterin, responsible cofactor to regulate eNOS activity increasing availability of NO.…”

Section: Statinsmentioning

confidence: 99%

“…The role of statins, atorvastatin, in cirrhotic portal hypertension was proved to be different than the one in non-cirrhotic portal hypertension. Statins inhibit non-canonical Hedgehog signalling and cirrhotic portal hypertension [5]. Atorvastatin for a short period can blunt neo angiogenesis in cirrhosis by non-canonical HedgeHoc signalling meanwhile in non-cirrhotic portal hypertension statin increases systemic and splanchnic neo angiogenesis by canonical way [8].…”

Section: Statinsmentioning

confidence: 99%

Statins in Cirrhotic Portal Hypertension – A Brief Review

Pollo-Flores¹,

Roever²

2016

Evidence Based Medicine and Practice

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Nowadays the cirrhosis physiopatology is being deeply studied and new pharmacology approach comes with new perspective of changing natural history and initial steps of the disease. The statins have many properties in this sense. These drugs have demonstrated effects improving portal hypertension, liver functions, hepatocellular carcinoma with few side effects. Its action mechanism happens predominantly in intrahepatic environment, what seems very attractive. Some studies were conducted in animals and very few in human beings. This brief review aim to address advantages of the use of statins in liver disease. One question still open is which statin is the best in liver disease and which population of cirrhotic profit the most of the drug.

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“…Recent studies have shown the possibilities of additional treatments; one is tetrahydrobiopterin, an eNOS cofactor, which increases eNOS activity and significantly improves the vasodilator response to acetylcholine in rats with cirrhosis [54]. It may have a potential role for the treatment of portal hypertension by improving the endothelial dysfunction.…”

Section: Endothelial Dysfunctionmentioning

confidence: 99%

Successful Bridging Hemostasis Using a Sengstaken-Blakemore Tube in Massive Rectal Variceal Bleeding

Kim

Suh

Kwon

2014

Korean J Crit Care Med

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Esophageal varices are the major complication of portal hypertension. It is detected in about 50% of cirrhosis patients, and approximately 5-15% of cirrhosis patients show newly formed varices or worsening of varices each year. The major therapeutic strategy of esophageal varices consists of primary prevention, treatment for bleeding varices, and secondary prevention, which are provided by pharmacological, endoscopic, interventional and surgical treatments. Optimal management of esophageal varices requires a clear understanding of the pathophysiology and natural history. In this paper, we outline the current knowledge and future prospect in the pathophysiology of esophageal varices and portal hypertension.

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Three-day tetrahydrobiopterin therapy increases in vivo hepatic NOS activity and reduces portal pressure in CCl4 cirrhotic rats

Cited by 45 publications

References 29 publications

Hesperidin protects against diethylnitrosamine/carbon tetrachloride-induced renal repercussions via up-regulation of Nrf2/HO-1 signaling and attenuation of oxidative stress

Hesperidin protects against diethylnitrosamine/carbon tetrachloride-induced renal repercussions via up-regulation of Nrf2/HO-1 signaling and attenuation of oxidative stress

Statins in Cirrhotic Portal Hypertension – A Brief Review

Successful Bridging Hemostasis Using a Sengstaken-Blakemore Tube in Massive Rectal Variceal Bleeding

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