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

Abstract

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 arginine methyltransferase-1 and decreased dimethylarginine dimethylaminohydrolase expression. BDL rats also exhibit renal and brain damage characterized by increased tissue ADMA concentrations. The increased plasma ADMA levels and multiple organ damages seen here are also observed following multiple organ failures associated with critical illness. This review discusses the dysregulation of ADMA in major organs in BDL rats and the role of increased ADMA in multiple organ damages.

The restorative effect of ascorbic acid on liver injury inducedby asymmetric dimethylarginine

“…ADMA also led to secretion of various factors and tissue damage by causing endothelial dysfunction. Increased levels of ADMA that inhibit NO synthesis were found to be associated with endothelial dysfunction, vasoconstriction, peripheral artery disease, coronary artery diseases, preeclampsia, hypertension, stroke, heart failure, chronic kidney failure, portal hypertension observed in the clinical picture of cirrhosis, diabetes mellitus, and insulin resistance in the patients with essential hypertension (Alacam et al, 2011;Sheen et al, 2014). It is known that ADMA increases in hepatic diseases; however, it is still controversial whether increased ADMA level is the reason for or the result of hepatic deterioration.…”

“…It is found in the literature that the ADMA/DDAH/NO pathway is considered responsible in the pathophysiology of many diseases (Sheen et al, 2014). This pathway is also blamed for the pathophysiology of hepatic diseases.…”

Asymmetric Dimethylarginine and Hepatic Encephalopathy: Cause, Effect or Association?

“…In addition, in the BDL rat model, ADMA level significantly raises in the peripheral blood, whereas the concentration of l -arginine decreases [51]. Of note in this context, the PRMT-1 protein content was elevated in the liver of BDL rats [52, 53], but reduced in BDL rat brain [46].…”

The Structural Bile Ducts Organization in the Pathological Conditions

“…Вступ. Від стану жовчних шляхів залежить здоров'я основної «фабрики» організмупечінки [1,2]. Пошкодження епітелію слизової оболонки жовчних проток, зумовлене аутоімунним дисбалансом, вірусною чи бактеріальною інфекцією, токсичними речовинами чи аномаліями розвитку, призводить до важких структурних змін печінки, обумовлюючи високу смертність [3].…”