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Advances in Pharmacological Sciences
Volume 2015, Article ID 298792, 7 pages
http://dx.doi.org/10.1155/2015/298792
Research Article

Can Chronic Nitric Oxide Inhibition Improve Liver and Renal Dysfunction in Bile Duct Ligated Rats?

Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Zagazig, Zagazig 44519, Egypt

Received 18 September 2015; Revised 27 October 2015; Accepted 9 November 2015

Academic Editor: Ismail Laher

Copyright © 2015 Mona Fouad Mahmoud et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The aims of the present work were to study the effects of chronic NO inhibition on liver cirrhosis and to analyze its relationship with liver and kidney damage markers. Two inhibitors of NO synthesis (inducible NO synthase (iNOS) inhibitor, aminoguanidine (AG), and nonselective NOS inhibitor, L-nitroarginine methyl ester (L-NAME)) were administered for 6 weeks to bile duct ligated (BDL) rats 3 days after surgery. The present study showed that BDL was associated with liver injury and renal impairment. BDL increased liver NO content and myeloperoxidase (MPO) activity. This was corroborated by increased oxidative stress, TNF-α, TGF-1β, and MMP-13 genes overexpression. Although both drugs reduced NO synthesis and TNF-α gene overexpression, only AG improved renal dysfunction and liver damage and reduced liver oxidative stress. However, L-NAME exacerbated liver and renal dysfunction. Both drugs failed to modulate TGF-1β and MMP-13 genes overexpression. In conclusion, inhibition of NO production by constitutive nitric oxide synthase (cNOS) plays a crucial role in liver injury and renal dysfunction while inhibition of iNOS by AG has beneficial effect. TNF-α is not the main cytokine responsible for liver injury in BDL model. Nitric oxide inhibition did not stop the progression of cholestatic liver damage.