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

نویسندگان

  • Andrea Ferrigno
  • Giuseppina Palladini
  • Alberto Bianchi
  • Vittoria Rizzo
  • Laura G Di Pasqua
  • Stefano Perlini
  • Plinio Richelmi
  • Mariapia Vairetti
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Increased Circulatory Asymmetric Dimethylarginine and Multiple Organ Failure: Bile Duct Ligation in Rat as a Model

Bile duct ligation (BDL)-treated rats exhibit cholestasis, increased systemic oxidative stress, and liver fibrosis, which ultimately lead to liver cirrhosis. Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of nitric oxide synthase that can decrease the synthesis of nitric oxide. BDL rats have higher plasma and hepatic ADMA levels, which may be due to increased hepatic protein argi...

متن کامل

The Study of Serum Asymmetric Dimethylarginine Concentrations in the Different Paraoxonase Phenotypes of Exudative Age-related Macular Degeneration Disease

Background and Aims: Age-related macular degeneration (ARMD) is a degenerative retinal disorder that causes progressive loss of central vision in older adults. The study aimed to determine the effect of asymmetric dimethylarginine (ADMA) as oxidizing metabolite and paraoxonase (PON1) activity within its phenotypes as an antioxidant agent in the development of such multifactorial disease. Mater...

متن کامل

Management of Hepatic Cholestasis

Hepatic cholestasis is characterized by elevated alkaline phosphatase and gama - glutamyl transpeptidase levels which is then followed by conjugated hyperbilirubinemia. It is classified into intrahepatic and extrahepatic cholestasis. Intrahepatic cholestasis indicates hepatocellular dysfunction or the presence of an obstructive lesion in intrahepatic bile ducts distal to biliary canalicular sy...

متن کامل

Role of matrix metalloproteinase II on analgesic effect of nitric oxide inhibition in rat

Abstract Introduction: Matrix metalloproteinase 2 is one of the inflammatory mediators that is involved in nociceptive processing and its production is regulated by many inflammatory factors such as nitric oxide. We studied the role of MMP-2 on the analgesic effects of nNOS inhibitor. Methods: Considering that nitric oxide has many roles in pain processing, we studied the CSF levels of MMP-2 ...

متن کامل

Nephrotoxicity of Isosorbide Dinitrate and Cholestasis in Rat: The Possible Role of Nitric Oxide

Background: Nitric oxide (NO), a major chemical form of endothelium-derived relaxing factor and an important regulator of vascular tone, is released by endothelial cells. The role of NO is not restricted to the vascular system, and it participates in the regulation of renal hemodynamics and renal excretory function. There are increasing evidences indicating that the elevated levels of NO play a...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 2014  شماره 

صفحات  -

تاریخ انتشار 2014