Leukotriene B4 limits the effectiveness of fish oil in an animal model of asthma.

This study aimed to evaluate the levels of eicosanoids derived from arachidonic acid (ARA) in the lungs of asthmatic rats supplemented with fish oil. The present data gives insight into the action of fish oil in asthma, related to its inability to modify the contractile capacity of tracheal smooth muscle reported previously in a model of asthma in rats. Male Wistar rats were supplemented daily with 1 g of fish oil/kg of body weight for 21 days. They were exposed to ovalbumin (OVA) after previous sensitization with OVA to induce asthma. Pulmonary levels of five eicosanoids were measured using immunoassay kits: PGE2, TXB2, LTB4, LXA4, and 8-iso PGF2α. In asthmatic rats, supplementation with fish oil resulted in lower concentrations of lung eicosanoids produced by cyclooxygenase-2 and 15-lipoxygenase: PGE2, TXB2, and LXA4, respectively. Fish oil supplementation also decreased the non-enzymatically produced eicosanoid 8-iso PGF2α. Fish oil supplementation did not affect LTB4, a metabolite of 5-lipoxygenase. The limited efficacy of fish oil supplementation in asthmatic rats is associated with a lack of action in reducing the levels of LTB4 in the lungs. Thus, fish oil differentially modulates the concentrations of eicosanoids derived from ARA via specific pathways in an animal model of asthma.

Fish oil supplementation decreases oxidative stress but does not affect platelet-activating factor bioactivity in lungs of asthmatic rats.

Dietary fish oil supplementation increases the content of n-3 polyunsaturated fatty acids (PUFA) in cellular membranes. The highly unsaturated nature of n-3 PUFA could result in an enhanced lipid peroxidation in the oxidative environment characteristic of asthma. The oxidative reaction cascade culminates in an increased production of components associated to oxidative stress and of an important proinflammatory mediator platelet-activating factor (PAF)-like lipid. We evaluated the effect of fish oil supplementation in asthmatic rats upon the PAF bioactivity and parameters related to oxidative stress in the lung. Fish oil supplementation of asthmatic rats resulted in lower concentrations of nitrite (1.719 ± 0.137 vs. 2.454 ± 0.163 nmol/mL) and lipid hydroperoxide (72.190 ± 7.327 vs. 120.200 ± 11.270 nmol/mg protein). In asthmatic animals, fish oil increased the activities of superoxide dismutase (EC 1.15.1.1) (33.910 ± 2.325 vs. 24.110 ± 0.618 U/mg protein) and glutathione peroxidase (EC 1.11.1.9) (164.100 ± 31.250 vs. 12.590 ± 5.234 U/mg protein). However, fish oil did not affect PAF bioactivity in lung tissue of asthmatic rats (0.545 ± 0.098 340/380 vs. 0.669 ± 0.101 340/380 nm ratio). Considering the two-step process--oxidative stress and PAF bioactivity--fish oil exhibited a divergent action on these aspects of asthmatic inflammation, since the supplement lowered oxidative stress in the lungs of asthmatic rats, presenting an antioxidant effect, but did not affect PAF bioactivity. This suggests a dual effect of fish oil on oxidative stress and inflammation in asthma.

The effectiveness of fish oil supplementation in asthmatic rats is limited by an inefficient action on ASM function.

Episodes of acute exacerbation are the major clinical feature of asthma and therefore represent an important focus for developing novel therapies for this disease. There are many reports that the n-3 fatty acids found in fish oil exert anti-inflammatory effects, but there are few studies of the action of fish oil on airway smooth muscle (ASM) function. In the present investigation, we evaluated the effect of fish oil supplementation on smooth muscle force of contraction in ovalbumin-induced asthmatic Wistar rats, and its consequences on static lung compliance, mucus production, leukocyte chemotaxis and production of proinflammatory cytokines. Fish oil supplementation suppressed the infiltration of inflammatory cells into the lung in asthmatic animals (2.04 ± 0.19 × 10(6) cells vs. 3.33 ± 0.43 × 10(6) cells in the control asthmatic group; P < 0.05). Static lung compliance increased with fish oil supplementation in asthmatic rats (0.640 ± 0.053 mL/cm H2O vs. 0.399 ± 0.043 mL/cm H2O; P < 0.05). However, fish oil did not prevent asthma-associated lung eosinophilia and did not affect the concentrations of tumor necrosis factor-α and interleukin-1ß in lung tissue or the proportion of the airways obliterated with mucus. Fish oil had no effect on the force of contraction in asthmatic rats in response to acetylcholine (3.026 ± 0.274 mN vs. 2.813 ± 0.364 mN in the control asthmatic group). In conclusion, although fish oil exerts some benefits in this model of asthma, its effectiveness appears to be limited by an inefficient action on airway smooth muscle function.