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BioMed Research International
Volume 2014 (2014), Article ID 327537, 8 pages
Research Article

Lobe-Specific Heterogeneity in Asymmetric Dimethylarginine and Matrix Metalloproteinase Levels in a Rat Model of Obstructive Cholestasis

1Department of Internal Medicine and Therapeutics, IRCCS S. Matteo Foundation, University of Pavia, 27100 Pavia, Italy
2Department of Molecular Medicine, IRCCS S. Matteo Foundation, University of Pavia, 27100 Pavia, Italy

Received 28 February 2014; Revised 23 May 2014; Accepted 26 May 2014; Published 12 June 2014

Academic Editor: Kim Bridle

Copyright © 2014 Andrea Ferrigno 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.


We investigated the effects of obstructive cholestasis in different hepatic lobes by evaluating asymmetric dimethylarginine (ADMA) (a nitric oxide synthase inhibitor), protein methyltransferase (PRMT) and dimethylarginine dimethylaminohydrolase (DDAH) (enzymes involved, resp., in its synthesis and degradation), the cationic transporter (CAT), and metalloproteinase (MMP) activity. Sixteen male Wistar rats underwent a 3-day cholestasis by common bile duct ligation (BDL) or sham operation. Blood samples and hepatic biopsies from left lobe (LL), median lobe (ML), and right lobe (RL) were collected. Serum hepatic enzymes, tissue ADMA, DDAH activity, CAT-2 protein, mRNA expression of DDAH and PRMT, and MMP-2 and MMP-9 activity were monitored. Cholestasis was confirmed by altered serum hepatic enzymes. Higher levels of tissue ADMA were detected in RL and ML as compared with LL. PRMT mRNA expression and DDAH activity did not differ among the lobes after BDL. CAT-2 levels are higher in the RL and ML in the sham-operated group. Higher activity in MMP-2 and MMP-9 was found in RL. In conclusion, after cholestasis an increase in hepatic ADMA in RL and ML was detected as well as tissue MMP-2 and MMP-9 activation in RL, supporting the evidence of functional heterogeneity among the liver lobes also occurring in an obstructive cholestasis model.