Abstract
Background/Aim: The liver is continuously linked to the gut via the portal vein supply. Gastrointestinal complications are directly associated with liver cirrhosis. Carbon tetrachloride (CCl4) caused liver toxicity is well documented in animal models, the very fewer search has been carried out on the intestinal damage in case of acute liver injury. Thus, this study aimed to investigate the intestinal alteration and subsequently the potential therapeutic role of Wheat Germ Oil (WGO) in the liver and small intestine after acute administration of CCl4. Material and Methods: Mice were randomly divided into 4 groups, control group, WGO group: received corn oil orally for 2 days then WGO (1400mg/kg) orally for 8 days, CCl4 group: received CCl4 orally for 2 days then corn oil for 8 days, CCl4 + WGO group: received CCl4 for 2 days then WGO for 8 days. Serum lipid profile, serum lactate dehydrogenase (LDH), intestinal oxidative stress enzymes, histopathological and DNA fragmentation assays were estimated. Results: Acute dose (50%, 1 mL/kg body weight) of CCl4-induced hyperlipidemia, hypocholesteremia, elevation in LDH, malondialdehyde (MDA), nitric oxide (NO) and intestinal DNA damage in addition to the reduction in the intestinal oxidative stress markers and an alteration in the mucosal architecture. On the contrary, WGO administration has the potency to protect not only the liver but also the small intestine in acute CCl4-induced tissue damage. The valuable effect is chiefly attributed to its mechanism of reducing the lipid profile and suppressing the oxidative stress that caused DNA damage Conclusion: WGO administration could markedly improve the liver and the small intestine from the CCl4 damage and consequently may be used as a therapeutic agent against the hepatic and intestinal toxicity.
Highlights
Carbon tetrachloride (CCl4) is commonly used for experimental induction of liver injury in rodents to mimic the oxidative stress situations in many pathophysiological conditions (Zhu et al, 2013; Go et al, 2016)
The valuable effect is attributed to its mechanism of reducing the lipid profile and suppressing the oxidative stress that caused DNA damage Conclusion: Wheat Germ Oil (WGO) administration could markedly improve the liver and the small intestine from the CCl4 damage and may be used as a therapeutic agent against the hepatic and intestinal toxicity
Assays kits for the detection of liver lipid profile and oxidative stress markers were purchased from Biodiagnostic (Giza, Egypt)
Summary
Carbon tetrachloride (CCl4) is commonly used for experimental induction of liver injury in rodents to mimic the oxidative stress situations in many pathophysiological conditions (Zhu et al, 2013; Go et al, 2016). Generation of free radicals has been observed in many tissues; liver, kidney, intestine, heart, lung, brain, and blood after CCl4 administration (Dashti et al, 1989). The free radicals generated from CCl4 and its metabolites induced an impairment of the endoplasmic reticulum (ER) and altered the permeability. As long as the gastrointestinal tract is affected, the mucosal alterations may arise, resulting in portal hypertension during liver cirrhosis (Llovet et al, 1994). Oxygen free radicals generated from CCl4 play an important role in the damage of gut epithelial cells, which may affect the gut barrier function, facilitate bacterial translocation and induce the release of endotoxin (Ramachandran et al, 2002). Oxidative stress in the intestinal mucosa caused an elevation in xanthine oxidase which is an important source of free radicals in the small intestine (Watkins 2001)
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