Diets with Beef Tallow Prevent Acute Acetaminophen Hepatotoxicity Compared to Diets with Soybean Oil in a Rat Model

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Dietary polyunsaturated fatty acids (PUFA) increase liver injury in response to ethanol feeding. We tested the hypothesis that diets rich in linoleic acid (18:2 n-6) would also affect acute liver injury after acetaminophen injection. To determine whether the types and quantity of dietary fats were important, we examined the effects of feeding diets with either 7 or 15 g per 100 g soybean oil or beef tallow. After the feeding period, animals were unfed and injected either with 600 mg/kg body weight acetaminophen suspended in gum arabic-based vehicle, or with vehicle alone. Samples of plasma and liver were taken for analyses of liver-specific enzymes, [glutamate-pyruvate transaminase (GPT) and glutamate-oxaloacetate transaminase (GOT)] and hepatic glutathione (GSH) and thiobarbituric reactive substances (TBARS) levels, respectively. Treatment with acetaminophen significantly elevated levels of plasma GOT and GPT as well as hepatic TBARS but reduced hepatic GSH levels in groups fed diets with soybean oil compared to beef tallow. The feeding regimens changed the ratio of 18:2 n-6 to oleic acid (18:1 n-9) in liver membrane phospholipid approximately 4- to 6-fold, and produced modest changes in arachidonic acid (20:4 n-6). We conclude that acetaminophen-induced hepatotoxicity can be protected with more saturated fatty acids (SFA)-rich diet but can be exacerbated with PUFA-rich diet by modulating the tissue fatty acid composition.