RESUMO
The mycotoxin zearalenone (ZEA) has strong estrogenic effects and elicits reproductive toxicity. Chrysin is a natural flavonoid found in many plant and has a broad range of pharmacological activities, including anticancer, antioxidant and anti-inflammatory. The present study aimed to investigate the potential protective effects of chrysin against ZEA toxicity. Mice received chrysin (5 or 20â¯mg/kg; i.g.) for ten days, and then received a single injection of ZEA (40â¯mg/kg). Two days thereafter, blood and testes were collected. ZEA decreased number and motility of sperm, plasma testosterone levels, enzymatic (glutathione peroxidase, glutathione reductase, glutathione-S-transferase) and non-enzimatic defenses (reduced glutathione). Moreover, ZEA increased 4-hydroxynonenal and 8-hydroxy-2'-deoxyguanosine levels, myeloperoxidase activity and levels of proinflammatory cytokines (interleukins-1ß and 6, tumor necrosis factor alpha). ZEA also decreased levels of anti-inflammatory cytokine interleukin-10 and increased activity of caspases 3 and 9. Chrysin treatment increased the number and motility of sperm, testosterone levels, restored antioxidant defenses and reduced the inflammation and apoptosis process. In summary, chrysin attenuated the toxic effects caused by ZEA in blood and testes of mice, suggesting a potential preventive treatment against the deleterious effects of ZEA.
Assuntos
Fertilidade/efeitos dos fármacos , Flavonoides/farmacologia , Substâncias Protetoras/farmacologia , Zearalenona/toxicidade , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Flavonoides/química , Masculino , Camundongos , Motilidade dos Espermatozoides/efeitos dos fármacos , Testosterona/sangueRESUMO
Male mice received lycopene for 10 days before a single oral administration of zearalenone (ZEA). After 48 h testes and blood were collected. Mice treated with lycopene/ZEA exhibited amelioration of the hematological changes. Lycopene prevented the reduction in the number and motility of spermatozoa and testosterone levels, indicating a protective effect in the testicular damage induced by ZEA. Lycopene was also effective in protecting against the decrease in glutathione-S-transferase, glutathione peroxidase, glutathione reductase and δ-aminolevulinic acid dehydratase activities caused by ZEA in the testes. Exposure of animals to ZEA induced modification of antioxidant and inflammatory status with increase of reduced glutathione (GSH) levels and increase of the oxidized glutathione, interleukins 1ß, 2, 6, 10, tumor necrosis factor-α and bilirubin levels. Lycopene prevented ZEA-induced changes in GSH levels and inhibited the processes of inflammation, reducing the damage induced by ZEA. Altogether, our results indicate that lycopene was able to prevent ZEA-induced damage in the mice.
Assuntos
Carotenoides/farmacologia , Inflamação/tratamento farmacológico , Substâncias Protetoras/farmacologia , Testículo/efeitos dos fármacos , Zearalenona/toxicidade , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/metabolismo , Bilirrubina/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Inflamação/metabolismo , Interleucinas/metabolismo , Licopeno , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Sintase do Porfobilinogênio/metabolismo , Testículo/patologia , Testosterona/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Zearalenona/administração & dosagemRESUMO
The administration of hesperidin elicits an antidepressant-like effect in mice by a mechanism dependent on an interaction with the L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway, whose stimulation is associated with the activation of potassium (K(+)) channels. Thus, this study investigated the involvement of different types of K(+) channels in the antidepressant-like effect of hesperidin in the mice tail suspension test (TST). The intracerebroventricular administration of tetraethylammonium (TEA, a nonspecific blocker of K(+) channels), glibenclamide (an ATP-sensitive K(+) channel blocker), charybdotoxin (a large- and intermediate-conductance calcium-activated K(+) channel blocker) or apamin (a small-conductance calcium-activated K(+) channel blocker) combined with a subeffective dose of hesperidin (0.01 mg/kg, intraperitoneally [i.p.]) was able to produce a synergistic antidepressant-like effect in the mice TST. Moreover, the antidepressant-like effect elicited by an effective dose of hesperidin (0.3 mg/kg, i.p.) in TST was abolished by the treatment of mice with pharmacological compounds K(+) channel openers (cromakalim and minoxidil). Results showed that the antidepressant-like effect of hesperidin in TST may involve, at least in part, the modulation of neuronal excitability through inhibition of K(+) channels and may act through a mechanism dependent on the inhibition of L-arginine-NO pathway.
Assuntos
Antidepressivos/farmacologia , Hesperidina/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio/fisiologia , Animais , Apamina/administração & dosagem , Arginina/farmacologia , Charibdotoxina/administração & dosagem , Sinergismo Farmacológico , Glibureto/administração & dosagem , Hesperidina/administração & dosagem , Elevação dos Membros Posteriores , Masculino , Camundongos , Bloqueadores dos Canais de Potássio/administração & dosagem , Bloqueadores dos Canais de Potássio/uso terapêutico , Canais de Potássio/efeitos dos fármacos , Tetraetilamônio/administração & dosagemRESUMO
In this study, we investigated the therapeutic effects of treatment with (R)-Se-phenyl thiazolidine-4-carboselenoate (Se-PTC), an organic selenium compound with antinociceptive properties, against mechanical and thermal hyperalgesia induced by brachial plexus avulsion (BPA), a neuropathic model in mice. The involvement of cannabinoid CB(1) and CB(2) receptors in the Se-PTC anti-hyperalgesic effect was also investigated. Se-PTC treatment at (25 and 50mg/kg, per oral, p.o.) lowered (BPA model) induced mechanical and thermal hyperalgesia in mice. Pretreatment with cannabinoid CB(1) (AM251; 1mg/kg, intraperitoneally, i.p.), or CB(2) (AM630; 3mg/kg, i.p.) receptor antagonists reverted the mechanical and thermal anti-hyperalgesic effect of Se-PTC (25mg/kg) in the BPA model. Selective CB(1) (ACEA, 10mg/kg, i.p.) and CB(2) (JWH-133, 10mg/kg, i.p.) receptor agonists lowered mechanical and thermal hyperalgesia in the BPA model, and this effect was prevented by selective CB(1) and CB(2) receptor antagonists. Gabapentin (70mg/kg, p.o.), positive control administration also lowered mechanical and thermal hyperalgesia in the BPA model. The results suggest that the mechanical and thermal hyperalgesia observed following BPA in mice is dependent on cannabinoid receptors. The results indicate that modulating cannabinoid receptors represent a valuable approach for the treatment of neuropathic pain. In conclusion, the results suggested that Se-PTC produces pronounced mechanical and thermal anti-hyperalgesic effects in neuropathic models in mice by modulating CB(1) and CB(2) receptors.