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The present study was designed to evaluate the protective effects of echinochrome (Ech) on intrahepatic cholestasis in rats induced by a single (i.p.) injection of alpha-naphthylisothiocyanate (ANIT) (75 mg/kg body weight). The rats were pre-treated orally for 48hr (one dose / 24hr) with Ech (1, 5 and 10 mg/kg body weight) or ursodeoxycholic acid (UDCA) 80 mg/kg body weight drug then, injected with ANIT. ANIT markedly increased serum activities of alanine amino transaminase (ALT), aspartate amino transaminase (AST) and alkaline phosphatase (ALP), which was accompanied by a massive inflammation of epithelial cells on bile duct at 24h after ANIT injection. ANIT also increased the levels of total protein (TP), total bilirubin (TB), direct bilirubin (DB), indirect bilirubin (IB), however decrease albumin content (ALB). In addition ANIT increased hepatic MDA and NO level and decreased GSH level and GST activity. The Ech exerted hepatoprotective and anticholestatic effects as assessed by a significant decrease in the activities of serum AST, ALT and ALP, and the levels of TP, TB, DB and IB as well as liver MDA level and NO level. In conclusion, Ech was found to possess hepatoprotective effect against intrahepatic cholestasis induced by hepatotoxin such as ANIT.

Background: Drug-induced hepatotoxicity is an extremely widespread condition and is responsible for a variety of pathological effects on the liver. It was reported that hepatotoxicity induced by angiotensin converting enzyme inhibitors (ACEIs) is cholestasis mediated hepatitis. Bradykinin-potentiating factor (BPF) is one of the natural ACEIs. Although prolonged treatment with ACEIs provides protection against liver injury, the effect of short-term treatment with ACEIs has not been fully elucidated before. Thereby, the present study sought to determine if transient ACE inhibition may exacerbate the hepatotoxicity caused by bile duct ligation (BDL) in rats., Methods: Twenty one Wistar rats were divided into 3 groups: Sham-operated group, bile duct ligated (BDL) rats, and BDL rats treated for short-term with BPF (1 μg/kg body weight) day after day for one week and biochemical parameters were measured. Also, we assessed expression level of ACE1 and detection of hepatotoxicity in the liver tissues of different groups., Results: There was a significant increase in liver enzymes, bilirubin levels, and oxidative stress in the BDL group after treatment with BPF as compared to BDL group. We found overexpression of ACE1 gene in BDL group compared to BPF and Sham-operated control group. Histopathological examination of liver treated with BPF showed severe degeneration hepatic architecture and hepatocytes as compared to BDL group. Collagen deposition increased after BPF treatment as compared to BDL groups., Conclusion: The present investigation suggests and recommends that short- term ACE inhibition pathway potentiates liver fibrosis during cholestasis disease., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Holothuria arenicola is the most important and abundant sea cucumber species in the Mediterranean Sea on the Egyptian coast. The present study aims to assess the anti-oxidative and anticholestatic effects of the sea cucumber Holothuria arenicola extract (HaE) in a model of bile duct ligation in male albino rats., Methods: Fifty four male Wistar albino rats were assigned into two main groups, the Sham-operated control and bile duct ligated (BDL) group. After 14 days of surgery, the animals of the group I (Sham control) received distilled water only for 7, 14 and 28 days. Second group (BDL group) was divided into 2 subgroups, animals of these subgroups treated for 7, 14 and 28 consecutive days as follow: subgroup I (BDL), rats of this subgroup administered distilled water orally. Subgroup II (HaE), animals of this subgroup treated orally with HaE (200 mg/kg body weight)., Results: The HaE revealed significant antifibrotic effect as evident by decreasing the levels of total conjugated and unconjugated bilirubin and the activities of serum aminotransferases (ASAT and ALAT) and alkaline phosphatase (ALP) as well as malondialdehyde (MDA) level, and increasing the serum albumin, glutathione reduced (GSH) levels. Treatment with HaE normalized the antioxidant enzyme, glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) activities activities., Conclusion: The present prospective study correlated the antifibrotic effect of HaE to its direct antioxidant effect that can be related to its contents of phenolic compounds specially chlorogenic acid, pyrogallol, rutin and coumaric acid.