sildenafil-citrate and Liver-Diseases--Alcoholic

Rats fed with ethanol and a nutritious diet intragastrically develop liver pathologic changes associated with cyclic elevation of blood and urinary ethanol levels (BAL and UAL cycle). At the peaks of the UAL cycle, the livers are hypoxic. When the liver portal hepatic blood flow is temporarily clamped for 2 min and then released, the livers at the peak UAL fail to recover completely compared to the control livers and the livers at the UAL cycle troughs. Viagra was fed to the ethanol-fed rats to enhance the effects of nitric oxide. Since nitric oxide is known to increase hepatic blood flow, it was anticipated that Viagra would prevent the liver hypoxia at the UAL cycle peaks and also improve the post-clamp recovery from the post-clamp ischemia challenge. Viagra tended to improve the post-clamp recovery of the liver surface pO2 levels of the ethanol-fed rats probably by slowing O2 consumption as result of NO inhibition of mitochondrial cytochrome c oxidase activity. However, Viagra increased the pathology score when fed with ethanol. For this reason, Viagra is a two-edged sword. On the one hand, it tended to be protective in the post-ischemic injury in the ethanol-fed rats and on the other hand, it enhanced the liver injury caused by ethanol. Viagra did not affect the UAL cycle.

Topics: Animals; Ethanol; Ischemia; Liver; Liver Diseases, Alcoholic; Male; Nitric Oxide; Oxygen; Piperazines; Purines; Rats; Rats, Wistar; Sildenafil Citrate; Sulfones; Vasodilator Agents

Sildenafil citrate is a potent inhibitor of specific phosphodiesterase-5, which mediates metabolism of intracellular second message -- cGMP. Sildenafil citrate has been widely used for erectile dysfunction in men. Moreover, it is known that men with liver diseases have higher rate of erectile dysfunction. Furthermore, it has been demonstrated that nitric oxide plays an important role in liver function and regeneration. The present study evaluates effects of sildenafil citrate on hepatic function and regeneration in normal and alcohol-fed rats. In normal rats sildenafil citrate has a trend to improve hepatic function after partial hepatectomy (PHx). Moreover, sildenafil citrate significantly reduces hepatic regenerative activity at the concentration of 5 mg/kg body weight. However, sildenafil had no effects on hepatic function and regeneration of alcohol-fed rats. In general, sildenafil citrate did not induce significant changes in hepatic function and regenerative activity after PHx in normal and alcohol-fed rats, except at concentration of 5 mg/kg sildenafil citrate significantly inhibit hepatic regeneration in normal rats.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Cyclic Nucleotide Phosphodiesterases, Type 5; Dose-Response Relationship, Drug; Ethanol; Gene Expression; Hepatectomy; Liver; Liver Diseases, Alcoholic; Liver Regeneration; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sildenafil Citrate; Sulfones