The effect of Viagra (sildenafil citrate) on liver injury caused by chronic ethanol intragastric feeding in rats

Li, J.; Fu, Paul; DeLeon, Marino; French, Barbara A.; French, Samuel W.

doi:10.1016/j.yexmp.2004.09.004

Cited by 17 publications

(8 citation statements)

References 30 publications

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“…The hepatoprotection afforded by sildenafil could to a certain extent be also related to hepatoproliferative properties that have been attributed to sildenafil and its downstream signaling pathway. In particular, sildenafil promoted hepatocellular regeneration in a rat model of liver injury caused by chronic ethanol feeding, manifested by a greater mitotic index of liver cells in sildenafil-treated rats [55]. In addition, sildenafil administration in a rat model of partial hepatectomy accelerated regeneration rate of the remnant mass, as expressed by cell proliferation markers and mitotic counts [56].…”

Section: Discussionmentioning

confidence: 99%

Sildenafil Attenuates Hepatocellular Injury after Liver Ischemia Reperfusion in Rats: A Preliminary Study

Savvanis

Nastos

Tasoulis

et al. 2014

Oxidative Medicine and Cellular Longevity

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We evaluated the role of sildenafil in a rat liver ischemia-reperfusion model. Forty male rats were randomly allocated in four groups. The sham group underwent midline laparotomy only. In the sildenafil group, sildenafil was administered intraperitoneally 60 minutes before sham laparotomy. In the ischemia-reperfusion (I/R) group, rats were subjected to 45 minutes of hepatic ischemia followed by 120 minutes of reperfusion, while in the sild+I/R group rats were subjected to a similar pattern of I/R after the administration of sildenafil, 60 minutes before ischemia. Two hours after reperfusion, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured and histopathological examination of the lobes subjected to ischemia as well as TUNEL staining for apoptotic bodies was performed. Additionally, myeloperoxidase (MPO) activity and the expression of intercellular adhesion molecule-1 (ICAM-1) were analyzed. Serum markers of hepatocellular injury were significantly lower in the sild+I/R group, which also exhibited lower severity of histopathological lesions and fewer apoptotic bodies, as compared to the I/R group. The I/R group showed significantly higher MPO activity and higher expression of ICAM-1, as compared to the sild+I/R group. Use of sildenafil as a preconditioning agent in a rat model of liver I/R exerted a protective effect.

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Section: Discussionmentioning

confidence: 99%

Sildenafil Attenuates Hepatocellular Injury after Liver Ischemia Reperfusion in Rats: A Preliminary Study

Savvanis

Nastos

Tasoulis

et al. 2014

Oxidative Medicine and Cellular Longevity

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“…What regulates this balance or distribution of NO production in ALD is not known. A recent study found that sildenafil was protective against the ethanol‐induced hypoxia via delivery of NO to increase blood flow; it also increased the pathology score, thus acting as a two‐edged sword 105…”

Section: Nitrosative Stressmentioning

confidence: 99%

Alcohol and Oxidative Liver Injury

2006

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Acute and chronic ethanol treatment has been shown to increase the production of reactive oxygen species, lower cellular antioxidant levels, and enhance oxidative stress in many tissues, especially the liver. Ethanol-induced oxidative stress plays a major role in the mechanisms by which ethanol produces liver injury. Many pathways play a key role in how ethanol induces oxidative stress. This review summarizes some of the leading pathways and discusses the evidence for their contribution to alcohol-induced liver injury. Many of the seminal reports in this topic have been published in HEPATOLOGY, and it is fitting to review this research area for the 25th Anniversary

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“…Erythropoietin is a glycoprotein that regulates red cell production, and functions as a rescue factor of red cells by increasing their survival and inhibiting their apoptosis in vitro (12). Sildenafil is an inhibitor of phosphodiesterase-5 and is widely used as a new class vasoactive drug that has a powerful effect against ischemia/reperfusion injury in several tissues of different animal models (13,14). In a previous study by our group (15), the protective effect of intraperitoneal injection of erythropoietin and sildenafil in adult rats that underwent testicular torsion and detorsion was investigated and compared.…”

Section: Introductionmentioning

confidence: 99%

Erythropoietin and sildenafil protect against ischemia/reperfusion injury following testicular torsion in adult rats

Kostakis

Zavras

Damaskos

et al. 2017

Experimental and Therapeutic Medicine

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Testicular torsion/detorsion causes severe tissue damage due to ischemia/reperfusion injury. The present study investigated the protective effect of erythropoietin and sildenafil against ischemia/reperfusion injury following unilateral testicular torsion/detorsion in adult rats. A total of 28 adult male rats were included, and were divided into the following groups: Group A (n=5), sham operated; groups B (n=5), C (n=5), D (n=5) and E (n=8), undergoing right testis torsion and detorsion after 90 min. Group B received no drug treatment. Rats in the groups C and D received low-dose (1,000 IU/kg) or high-dose (3,000 IU/kg) erythropoietin, while those in group E received sildenafil (0.7 mg/kg), through intraperitoneal injection after 60 min of torsion. The right testis was extracted 24 h after detorsion, and the tissue was subjected to histopathological examination and immunohistochemical assessment of cleaved caspase-3 expression. Histological alterations and the quality of spermatogenesis were scored according to the Cosentino and the Johnsen scoring systems, respectively. The results demonstrated normal testicular architecture in group A, while the other groups showed ischemic cellular damages, with the worst scores observed in group B. Groups D and E presented better scores compared with group C. Regarding the quality of spermatogenesis, the best scores were observed in group A, and the worst in group B. Groups C, D and E presented similar results, which were improved in comparison to group B, however, not compared to group A. Furthermore, cleaved caspase-3 levels were lower in groups A, D and E, with equal results observed. Group C had higher levels of cleaved caspase-3 compared with these groups, but lower than group B, which presented the highest cleaved caspase-3 levels. In conclusion, erythropoietin and sildenafil protect testis from ischemia/reperfusion injury by decreasing cellular damage and attenuating apoptosis.

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The effect of Viagra (sildenafil citrate) on liver injury caused by chronic ethanol intragastric feeding in rats

Cited by 17 publications

References 30 publications

Sildenafil Attenuates Hepatocellular Injury after Liver Ischemia Reperfusion in Rats: A Preliminary Study

Sildenafil Attenuates Hepatocellular Injury after Liver Ischemia Reperfusion in Rats: A Preliminary Study

Alcohol and Oxidative Liver Injury

Erythropoietin and sildenafil protect against ischemia/reperfusion injury following testicular torsion in adult rats

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