RESUMO

Malathion is an organophosphate pesticide widely used for agricultural crops and for vector control of Aedes aegypti. Humans are exposed to this environmental contaminant by ingesting contaminated food. The juvenile and peripubertal periods are critical for the postnatal development of the epididymis and are when animals are most vulnerable to toxic agents. Since juveniles and adolescents are developing under exposure to the insecticide malathion, the aim of the present study was to evaluate the effects of exposure to low doses of malathion on postnatal epididymal development in rats. Male Wistar rats were exposed to malathion daily via gavage at doses of 10 mg kg-1 (M10 group) or 50 mg kg-1 (M50 group) for 40 days (postnatal days (PNDs) 25-65). The control group received the vehicle (0.9% saline) under the same conditions. On PND 40, the epididymides were removed, weighed and used for histological analysis and determination of the inflammatory profile and sperm count. Sperm from the vas deferens were subjected to sperm motility analysis. The M50 group showed tissue remodelling in the caput and cauda epididymides and increased neutrophil and macrophage migration in the caput epididymis. The M10 group showed decreased motile spermatozoa and IL-6 levels in the caput epididymis. Both doses decreased the IL-1ß level and altered the morphology of the same region. These results show that malathion exposure may impair postnatal epididymal development. Furthermore, alterations of the immune system in the epididymal environment are presented as new findings regarding the action of malathion on the epididymis.

Assuntos

Epididimo/efeitos dos fármacos , Inseticidas/toxicidade , Malation/toxicidade , Animais , Citocinas/imunologia , Epididimo/imunologia , Epididimo/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Ratos Wistar , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia

RESUMO

BACKGROUND: Lipoxin A4 (LXA4) is a metabolic product of arachidonic acid. Despite potent anti-inflammatory and pro-resolution activities, it remains to be determined if LXA4 has effect on ultraviolet (UV) radiation-induced skin inflammation. OBJECTIVE: To investigate the effects of systemic administration with LXA4 on UV radiation-induced inflammation and oxidative damage in the skin of mice. METHODS: Varied parameters of inflammation and oxidative stress in the skin of mice were evaluated after UV radiation (4.14 J/cm2). RESULTS: Pretreatment with LXA4 significantly inhibited UV radiation-induced skin edema and myeloperoxidase activity. LXA4 efficacy was enhanced by increasing the time of pre-treatment to up to 72 h. LXA4 reduced UV radiation-induced skin edema, neutrophil recruitment (myeloperoxidase activity and LysM-eGFP+ cells), MMP-9 activity, deposition of collagen fibers, epidermal thickness, sunburn cell counts, and production of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6 and IL-33). Depending on the time point, LXA4 increased the levels of anti-inflammatory cytokines (TGF-ß and IL-10). LXA4 significantly attenuated UV radiation-induced oxidative damage returning the oxidative status to baseline levels in parameters such as ferric reducing ability, scavenging of free radicals, GSH levels, catalase activity and superoxide anion production. LXA4 also reduced UV radiation-induced gp91phox [nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) subunit] mRNA expression and enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target enzyme nicotinamide adenine dinucleotide (phosphate) quinone oxidoreductase (Nqo1) mRNA expression. CONCLUSION: LXA4 inhibited UV radiation-induced skin inflammation by diminishing pro-inflammatory cytokine production and oxidative stress as well as inducing anti-inflammatory cytokines and Nrf2.