Improvement in survival to endotoxin has been seen after pretreatment with cyclooxygenase inhibitors. Because eicosapentaenoic acid (EPA), found in menhaden oil, competitively inhibits cyclooxygenase, we fed two groups of guinea pigs diets, in which the fat source was either menhaden or safflower oil, for 6 wk. A third group was allowed the safflower oil diet ad libitum. Menhaden oil-fed animals showed enhanced survival compared with safflower oil control animals 20 h after endotoxin (87 vs 63%, p less than 0.05). Ad libitum-fed safflower oil animals survived least well, with 47% alive at 20 h (p less than 0.005 vs menhaden oil group). We conclude that feeding animals a diet whose predominant lipid source is fish oil significantly improves survival after endotoxin. Dietary fat should be viewed not only as a caloric source but as a pharmacologically active substance that can have profound effects on the host's response to toxic insults.

The data suggest that dietary arginine supplementation decreases the mRNA expression of inflammatory cytokines in organs and improves the survival rate after thermal injury.

The effect of a nucleoside-nucleotide mixture on liver injury of rats induced by D-galactosamine was studied by examining changes in function and histopathology of the liver. Animals with liver damage received total parenteral nutrition with glucose and amino acids supplemented with a nucleoside-nucleotide mixture containing inosine, cytidine, GMP, uridine and thymidine, or with uridine which inhibits galactosamine injury, or with liver cell extract containing flavin adenine dinucleotide and nucleic acid derivatives. As control, animals with liver damage received total parenteral nutrition with glucose and amino acids only. The serum GOT and GPT concentrations were significantly lower in the group supplemented with nucleoside-nucleotide mixture than those in other groups. A large dose (1.2 g/kg) of uridine inhibited liver injury, but a lower dose (0.14 g/kg) did not have any effect, whereas nucleoside-nucleotide mixture containing the same amount of uridine inhibited the injury. Liver cell extract also did not improve liver function. Thus infusion of a physiological and balanced mixture of nucleosides or nucleotides may improve liver function in rats with liver injury.

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