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Background: Some studies have suggested that mitochondrial dysfunction and a superoxide imbalance could increase susceptibility to chronic stressful events, contributing to the establishment of chronic inflammation and the development of mood disorders. The mitochondrial superoxide imbalance induced by some molecules, such as rotenone, could be evolutionarily conserved, causing behavioral, immune, and neurological alterations in animals with a primitive central nervous system., Objective: Behavioral, immune, and histological markers were analyzed in Eisenia fetida earthworms chronically exposed to rotenone for 14 days., Methods: Earthworms were placed in artificial soil containing 30 nM of rotenone distributed into a plastic cup that allowed the earthworms to leave and return freely into the ground. Since these organisms prefer to be buried, the model predicted that the earthworms would necessarily have to return to the rotenone-contaminated medium, creating a stressful condition. The effect on survival behavior in the immune and histological body wall and ventral nervous ganglia (VNG) structures, as well as gene expression related to inflammation and mitochondrial and neuromuscular changes., Results: Rotenone-induced loss of earthworm escape behavior and immune alterations indicated a chronic inflammatory state. Some histological changes in the body wall and VNG indicated a possible earthworm reaction aimed at protecting against rotenone. Overexpression of the nicotinic acetylcholine receptor gene (nAChR α5) in neural tissues could also help earthworms reduce the degenerative effects of rotenone on dopaminergic neurons., Conclusion: These data suggest that mitochondrial dysfunction could be an evolutionarily conserved element that induces inflammatory and behavioral changes related to chronic stress., Competing Interests: Conflicts of interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2022 IBRO. Published by Elsevier Ltd. All rights reserved.)

A passive Arthus reaction (AR) induced in the peritoneal cavity of mice was followed by increased local vascular permeability and haemoconcentration. The intensity of the increased vasopermeability was higher in BALB/c compared with C3H/HePas mice despite the latter being 10 times more sensitive to platelet-activating factor (PAF). C3H/HePas mice however, exhibited higher levels of haemoconcentration and shock-like symptoms. Both events were inhibited by the PAF antagonist, WEB 2170. Indomethacin reduced both pathological events whereas L663,536, that inhibits leukotrienes synthesis reduced haemoconcentration but only in BALB/c mice. PAF was released into the peritoneal cavity, peak release being at 10 min after induction of AR. Prostaglandin E2 (PGE2), thromboxane B2 (TXB2), leukotriene B4 (LTB4), and leukotriene C4/D4 (LTC4/D4) were also released at this time. Similar levels of PAF and eicosanoids were found in BALB/c and C3H/HePas mice except for LTB4, which was higher in C3H/HePas. It is concluded that PAF and eicosanoids are mediators of local and systemic changes induced by immune complexes in the peritoneal cavity of mice.

We investigated the contribution of eicosanoids, platelet-activating factor, tumor necrosis factor and nitric oxide to the neutrophil influx and development of pulmonary haemorrhagic lesions following immune-complex-induced pneumonitis in rats and possible interactions between these mediators. Increased levels of leukotriene B4 and tumor necrosis factor, measured by enzyme immunoassay and L-929 cytotoxicity assay, were found in the bronchoalveolar lavage 1 and 4 h after induction of the reaction, respectively, and their release was dependent on the previous generation of platelet activating factor. Antagonism of leukotriene B4 receptors by RO-0254094 (2-[(5-carboxypentyl])oxy]-6-[6-[3,4-dihydro-4-oxo-8-propyl-2H-1-benzopy ran-7-yl)oxy]hexyl] benzenepropanoic acid), inhibition of nitric oxide synthesis by L-NAME (Nw-nitro-L-arginine methyl ester) and antagonism of PAF-receptors by WEB-2170 (5-(2-chlorphenyl)-3-4-dihydro-10-methyl-3-((4-morpholinyl)carbony l)-2 H,7H-cyclopenta (4,5)thieno(3,2-f)(1,2,4)-triazolo-4,3,a)91,4)diazepine), significantly inhibited the intensity of haemorrhage, evaluated by the increased levels of extravascular hemoglobin in homogenates of lung tissues. Little evidence support the role of tumor necrosis factor in these lesions. The infiltration of neutrophils, evaluated by measuring myeloperoxidase in homogenates of lungs, was reduced by compounds L-663,536 (3-[1-(4 chlorobenzyl)-3-t-butyl thio-5-isopropylindol-2-yl]-2-2-dimethylpropanoic acid), WEB-2170 and L-NAME. These results indicate that neutrophil infiltration and haemorrhagic lesions in immune-complex-induced lung inflammation are mediated by platelet activating factor, leukotriene B4 and nitric oxide and point out to interesting interactions between these mediators.

1. The interference of propylene glycol with anti-inflammatory effects of phenylbutazone was investigated. 2. Inhibitory effect of phenylbutazone on both carrageenin-induced edema and the cotton pellet granuloma was increased when propylene glycol was used as solvent. 3. Propylene glycol given alone inhibited carrageenin-induced edema and pleurisy, as well as granulomatous tissue formation. 4. Some pharmacokinetic parameters of phenylbutazone were also changed by propylene glycol administered simultaneously. 5. These results suggest that propylene glycol probably increases the anti-inflammatory effect of phenylbutazone by summation and by raising the plasma half-life and the distribution volume of phenylbutazone.