RESUMO
Ischaemia-reperfusion (IR) is the most common form of testicular injury that results in oxidative damage and inflammation ending by subinfertility. Paeonol, a natural phenolic compound, exhibits antioxidant and anti-inflammatory effects. Thus, the present study investigated the role of paeonol in rat testicular IR injury. Thirty adult Wistar rats were randomly divided into five groups; sham, sham treated with paeonol, IR injury, and IR pre-treated with paeonol at low and high doses. Serum testosterone and testicular levels of malondialdehyde and reduced glutathione (GSH) besides superoxide dismutase (SOD) activity were determined. Gene quantifications for tumour necrosis factor-α (TNF-α), hypoxia-inducible factor-1α (HIF-1α) and heat shock protein 70 (HSP70) were also assessed. Histopathological pictures and the immunohistochemical expression of testicular nuclear factor erythroid 2-related factor 2 (Nrf2), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) were shown. Pre-treatment with paeonol prevented the drop in serum testosterone, alongside with improvement of testicular malondialdehyde and GSH levels plus SOD activity. Paeonol regained the normal spermatogenesis with prevention of IR-induced increase in TNF-α, HIF-1α and HSP70 gene expression besides IL-1ß and IL-6 immunostaining and reduction in Nrf2 protein expression. Paeonol exerted a dose-dependent beneficial effect on testicular IR injury. This effect was achieved by its antioxidant and anti-inflammatory effects.
Assuntos
Acetofenonas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Traumatismo por Reperfusão/metabolismo , Torção do Cordão Espermático/metabolismo , Testículo/efeitos dos fármacos , Animais , Expressão Gênica/efeitos dos fármacos , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Proteínas de Choque Térmico HSP70/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imuno-Histoquímica , Inflamação/metabolismo , Inflamação/patologia , Interleucina-1beta/efeitos dos fármacos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Malondialdeído/metabolismo , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , Traumatismo por Reperfusão/patologia , Torção do Cordão Espermático/patologia , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Testículo/metabolismo , Testículo/patologia , Testosterona/metabolismo , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: We aimed to assess the protective role of verapamil, L-type calcium channel blockers, against early lung damage in diabetic rats. Lung injury has recently been recognized as a consequent complication of diabetes mellitus. Hyperglycemia induces inflammatory changes in lung tissue early in the disease. METHODS: Twenty four adult male rats were grouped into control, diabetic, diabetic treated with verapamil, and verapamil control. Streptozotocin (STZ) was used to induce diabetes. Oxidative parameters and antioxidative mechanisms were assessed in lung homogenate. Tumor necrosis factor alpha (TNFα) protein was measured as a pro-inflammatory mediator. Signal transducer and activator of transcription 3 (STAT3) gene expression and nuclear erythroid factor 2 (Nrf2) immunoexpression were screened. RESULTS: The lung showed oxidative damage and inflammatory infiltration in STZ diabetic rats early at 2 weeks. The parameters significantly improved in lung tissue treated with verapamil. Histopathology of the lung tissue confirmed the results. Inhibition of STAT3/TNFα pathway was involved in the protection offered by verapamil. Activation of Nrf2 together with an increasing antioxidant capacity of diabetic lung significantly ameliorates the injury induced by diabetes. CONCLUSIONS: Verapamil afforded protection in diabetic lung injury. The protection was mediated by the anti-inflammatory and antioxidant effects of verapamil.
