Nutr Res Pract.  2009 Jun;3(2):95-101.

Diets with corn oil and/or low protein increase acute acetaminophen hepatotoxicity compared to diets with beef tallow in a rat model

• Hwang J

Abstract

It has been reported that dietary polyunsaturated fats (PUFA) increase liver injury in response to ethanol feeding. We tested the hypothesis that diets rich in linoleic acid (18:2n-6) would affect acute liver injury after acetaminophen injection and that protein restriction might exacerbate the liver injury. We examined effects of feeding diets with either 15% (wt/wt) corn oil or 14% beef tallow and 1% corn oil for six weeks with either 6 or 20 g/100 g protein on acute hepatotoxicity. After the feeding period, liver injury was induced by injecting either with 600 mg/kg body weight acetaminophen suspended in gum arabic-based vehicle, or with vehicle alone during fasting status. Samples of liver and plasma were taken for analyses of hepatic glutathione (GSH) levels and liver-specific enzymes [(Glutamate-pyruvate transaminase (GPT) and glutamate-oxaloacetate transaminase (GOT)], respectively. Whereas GSH level was significantly lower in only group fed 15% corn oil with 6 g/100 g protein among acetaminophen-treated groups, activities of GPT and GOT were significantly elevated in all groups except the one fed beef tallow with 20 g/100 g protein, suggesting low protein might exacerbate drug-induced hepatotoxicity. The feeding regimens changed the ratio of 18:2n-6 to oleic acid (18:1n-9) in total liver lipids approximately five-fold, and produced modest changes in arachidonic acid (20:4n-6). We conclude that diets with high 18:2n-6 promote acetaminophen-induced liver injury compared to diets with more saturated fatty acids (SFA). In addition, protein restriction appeared to exacerbate the liver injury.

Keyword

Fatty acid composition; linoleic acid; saturated fatty acid; acetaminophen; hepatotoxicity

MeSH Terms

Acetaminophen
Animals
Arachidonic Acid
Body Weight
Corn Oil
Diet
Ethanol
Fasting
Fats
Fatty Acids
Gingiva
Glutathione
GTP-Binding Proteins
Linoleic Acid
Liver
Oleic Acid
Plasma
Rats
Zea mays
Acetaminophen
Arachidonic Acid
Corn Oil
Ethanol
Fats
Fatty Acids
GTP-Binding Proteins
Glutathione
Linoleic Acid
Oleic Acid

Figure

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  Fig. 1 The effect of acetaminophen on plasma levels of the liver enzymes, GPT (panel A) and GOT (panel B). Abbreviations: Group 1, 15% corn oil + 6% protein; Group 2, 15% corn oil + 20% protein; Group 3, 14% beef tallow + 1% corn oil + 6% protein; Group 4, 14% beef tallow + 1% corn oil + 20% protein; GA, gum arabic vehicle injected to control group; APAP, acetaminophen injected to case group. Each bar represents the mean ± SE (n=8). Different letters (a, b & c) indicate significant difference among APAP groups (*p<0.05, **p<0.01).

• 

  Fig. 2 The effect of acetaminophen on GSH levels. Abbreviations: Group 1, 15% corn oil + 6% protein; Group 2, 15% corn oil + 20% protein; Group 3, 14% beef tallow + 1% corn oil + 6% protein; Group 4, 14% beef tallow + 1% corn oil + 20% protein; GA, gum arabic vehicle injected to control group; APAP, acetaminophen injected to case group. Each bar represents the mean ± SE (n=8). **p<0.01 compared with GA and APAP groups in the same group. Different letters (a, b & c) indicate significant difference among APAP groups (*p<0.05).

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