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

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.

Keywords: Fatty acid composition; acetaminophen; hepatotoxicity; linoleic acid; saturated fatty acid.

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).