Evidence for the involvement of 5-lipoxygenase products in ethanol-induced intestinal plasma protein loss

In this study we investigated whether the products of 5-lipoxygenase (5-LO) were involved in the jejunal microvascular injury induced by intraluminal ethanol (ETH). A group of rabbits was given orally a selective inhibitor of 5-LO (L-651,392, Merck Frosst Canada) in two 10-mg doses, 24 and 2 h before the experiments (treated group). Another group received no such treatment (untreated group). In each animal of both groups, a jejunal segment was perfused with a control solution (control segment) and an adjacent segment with an ETH-containing (6% wt/vol) solution (ETH-perfused segment). In a series of experiments, we measured 5-LO activity of the jejunal segments of both groups using the generation of leukotriene B4 (LTB4) as an index. In a second series of experiments, we determined the ETH-induced intraluminal protein loss, which was taken as a measure of mucosal microvascular damage. In the untreated group, LTB4 generation (pg/mg tissue) by the ETH-treated segment (2.49 +/- 0.70) was higher (P less than 0.005) than that by the control segment (0.68 +/- 0.14). In the treated group, the LTB4 generation decreased (P less than 0.05) both in the control (0.15 +/- 0.03) and the ETH-perfused segments (0.44 +/- 0.09), but the difference between the two segments still remained significant. ETH caused a 13-fold increase (P less than 0.01) in jejunal protein loss in the untreated group but only a 5-fold increase (P less than 0.05) in the treated group. The ETH-induced increase in protein loss was significantly lower in the treated than in the untreated group (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)