Dietary saturated and monounsaturated fats protect against acute acetaminophen hepatotoxicity by altering fatty acid composition of liver microsomal membrane in rats

Jinah Hwang,Hye Hwang,Soo Kim,Yun-Hee Chang,Jung Park,Haeyon Chung,Eugene Shim

doi:10.1186/1476-511x-10-184

Jinah Hwang, Hye Hwang + Show 5 more

Open Access

https://doi.org/10.1186/1476-511x-10-184

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Abstract

BackgroundDietary polyunsaturated fats increase liver injury in response to ethanol feeding. We evaluated the effect of dietary corn oil (CO), olive oil (OO), and beef tallow (BT) on fatty acid composition of liver microsomal membrane and acute acetaminophen hepatotoxicity.MethodsMale Sprague-Dawley rats were fed 15% (wt/wt) CO, OO or BT for 6 weeks. After treatment with acetaminophen (600 mg/kg), samples of plasma and liver were taken for analyses of the fatty acid composition and toxicity.ResultsTreatment with acetaminophen significantly elevated levels of plasma GOT and GPT as well as hepatic TBARS but reduced hepatic GSH levels in CO compared to OO and BT groups. Acetaminophen significantly induced protein expression of cytochrome P450 2E1 in the CO group. In comparison with the CO diet, lower levels of linoleic acid, higher levels of oleic acids and therefore much lower ratios of linoleic to oleic acid were detected in rats fed OO and BT diets.ConclusionsDietary OO and BT produces similar liver microsomal fatty acid composition and may account for less severe liver injury after acetaminophen treatment compared to animals fed diets with CO rich in linoleic acid. These findings imply that types of dietary fat may be important in the nutritional management of drug-induced hepatotoxicity.

Highlights

Dietary saturated fatty acids (SFA) in beef and pork are protective against alcohol-induced liver disease in man and animals, whereas polyunsaturated fatty acids (PUFA) from corn oil and fish oil augment hepatic fibrosis and necrosis in rats fed a liquid diet containing alcohol [1,2,3,4]
The present study indicates that diets high in SFA or monounsaturated fatty acids (MUFA) decreased in vivo susceptibility to hepatotoxicity compared to diets high in linoleic acid
In conclusion, the present study confirms that druginduced liver injury is promoted by substitution of PUFA from rich sources such as corn oil for fatty acids derived from beef tallow and olive oil

Summary

Introduction

Dietary saturated fatty acids (SFA) in beef and pork are protective against alcohol-induced liver disease in man and animals, whereas polyunsaturated fatty acids (PUFA) from corn oil and fish oil augment hepatic fibrosis and necrosis in rats fed a liquid diet containing alcohol [1,2,3,4]. The cytochrome P450 (CYP)-dependent liver microsomal mixed function oxidase (MFO) system, which exists in membrane vesicles of the endoplasmic reticulum, plays an important role in the metabolism of various drugs and foreign compounds This system is responsible for activating acetaminophen in the liver to an electrophilic intermediate that can bind covalently to cellular macromolecules to produce cell damage [6]. The activity of this system affected by nutrients and lipid is one of the important factors because dietary fats can be reflected in the fatty acid composition of membrane phospholipids and alter the membrane conformation and fluidity, resulting in changes in the MFO activity [7]. We evaluated the effect of dietary corn oil (CO), olive oil (OO), and beef tallow (BT) on fatty acid composition of liver microsomal membrane and acute acetaminophen hepatotoxicity

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