Can Chronic Nitric Oxide Inhibition Improve Liver and Renal Dysfunction in Bile Duct Ligated Rats?
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-nitr...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Advances in Pharmacological Sciences |
| Online Access: | http://dx.doi.org/10.1155/2015/298792 |
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| author | Mona Fouad Mahmoud Sara Zakaria Ahmed Fahmy |
| author_facet | Mona Fouad Mahmoud Sara Zakaria Ahmed Fahmy |
| author_sort | Mona Fouad Mahmoud |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-26073b3621964c51ab8524a1b3bb5530 |
| institution | Kabale University |
| issn | 1687-6334 1687-6342 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advances in Pharmacological Sciences |
| spelling | doaj-art-26073b3621964c51ab8524a1b3bb55302025-02-03T01:11:26ZengWileyAdvances in Pharmacological Sciences1687-63341687-63422015-01-01201510.1155/2015/298792298792Can Chronic Nitric Oxide Inhibition Improve Liver and Renal Dysfunction in Bile Duct Ligated Rats?Mona Fouad Mahmoud0Sara Zakaria1Ahmed Fahmy2Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Zagazig, Zagazig 44519, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, University of Zagazig, Zagazig 44519, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, University of Zagazig, Zagazig 44519, EgyptThe 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.http://dx.doi.org/10.1155/2015/298792 |
| spellingShingle | Mona Fouad Mahmoud Sara Zakaria Ahmed Fahmy Can Chronic Nitric Oxide Inhibition Improve Liver and Renal Dysfunction in Bile Duct Ligated Rats? Advances in Pharmacological Sciences |
| title | Can Chronic Nitric Oxide Inhibition Improve Liver and Renal Dysfunction in Bile Duct Ligated Rats? |
| title_full | Can Chronic Nitric Oxide Inhibition Improve Liver and Renal Dysfunction in Bile Duct Ligated Rats? |
| title_fullStr | Can Chronic Nitric Oxide Inhibition Improve Liver and Renal Dysfunction in Bile Duct Ligated Rats? |
| title_full_unstemmed | Can Chronic Nitric Oxide Inhibition Improve Liver and Renal Dysfunction in Bile Duct Ligated Rats? |
| title_short | Can Chronic Nitric Oxide Inhibition Improve Liver and Renal Dysfunction in Bile Duct Ligated Rats? |
| title_sort | can chronic nitric oxide inhibition improve liver and renal dysfunction in bile duct ligated rats |
| url | http://dx.doi.org/10.1155/2015/298792 |
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