Effect of type of dietary fat and ethanol on antioxidant enzyme mRNA induction in rat liver.

A A Nanji,B Griniuviene,S M Sadrzadeh,S Levitsky,J D Mccully

doi:10.1016/s0022-2275(20)40059-8

Abstract

We carried out a study to relate the effect of the type of dietary fat and ethanol on antioxidant enzyme mRNA levels in liver in the intragastric feeding rat model. Different types of dietary fat were administered [saturated fat (SE), corn oil (CE) and fish oil (FE)] with ethanol to induce varying severities of liver injury. Ethanol-fed rats were pair-fed with dextrose-fed controls that received isocaloric amounts of dextrose. All animals were killed at 1 month and the following studies were carried out: evaluation of severity of pathologic liver injury, mRNA quantitation for catalase, glutathione peroxidase (GPx), and manganese superoxide dismutase (MnSOD), microsomal conjugated dienes, and hydrogen peroxide. SE animals had no liver injury, FE animals had severe liver injury, and CE animals had moderate liver injury. Ethanol induced GPx mRNA in all dietary groups, with the highest levels seen in the FE group. The pattern of catalase mRNA induction was similar to that of GPx mRNA. In contrast, MnSOD mRNA was decreased compared to controls in animals that developed pathologic liver injury, i.e., CE and FE groups. A positive correlation was seen between conjugated diene levels and GPx mRNA (r = 0.88, P < 0.01) and catalase mRNA. The similar slopes for the relationship between conjugated dienes and catalase in the fish oil and non-fish oil groups indicate that the same degree of lipid peroxidation increases catalase mRNA to a greater degree in fish oil-fed rats. A positive correlation was also seen between catalase mRNA and H2O2 (r = 0.95, P < 0.001).

Highlights

We carried out a study to relate the effect of the type of dietary fat and ethanol on antioxidant enzyme messenger RNA (mRNA) levels in liver in the intragastric feeding rat model
Based on our previous epidemiologic observations relating the type of dietary fat to alcoholic liver disease [17, 18],we carried out studies using the intragastric feeding model where we demonstrated that animals fed corn oil and ethanol develop pathologic changes in liver whereas animals fed saturated fat are protected [19, 20]
The most severe pathology was seen in the fish oil-ethanol (FE) group (Fig. l), moderate to severe changes were seen in the corn oil-ethanol (CE) group (Fig. 2), and no pathologic changes were seen in the saturated fat-ethanol group (Fig. 3)

Summary

Introduction

We carried out a study to relate the effect of the type of dietary fat and ethanol on antioxidant enzyme mRNA levels in liver in the intragastric feeding rat model. Generation of oxygen metabolites such as superoxide (02-h)y,drogen peroxide, and hydroxyl radicals is believed to be important in the pathogenesis of alcoholic liver injury [5, 6] To counteract these oxidants, cells have several antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase [7,8,9]. To relate antioxidant enzyme mRNA induction to ethanol-induced pathologic changes in the liver, we used the intragastric feeding rat model for alcoholic liver disease [15, 16]. This is an extremely useful model in which alterations in mRNA levels can be related to severity of pathologic changes.

Methods

Results

Conclusion