RESUMO
The effect of melatonin, a major secretory product of the pineal gland, in attenuation of propoxur (2-isopropoxy phenyl N-methyl carbamate)-induced modulation of cell-mediated immune (CMI) response was studied in rats. Male Wistar albino rats were exposed to propoxur (a widely used pesticide) orally (10 mg/kg) and/or melatonin (10 mg/kg) orally for 4 weeks. CMI was measured by delayed-type hypersensitivity (DTH), leucocyte and macrophage migration inhibition (LMI and MMI) responses and estimation of cytokines TNF-alpha and IFN-gamma levels. Rats exposed to propoxur for 4 weeks showed significant decrease in DTH, LMI and MMI responses. Propoxur also suppressed TNF-alpha and IFN-gamma production significantly. Administration of melatonin alone caused a significant increase in DTH response. Although there were no changes in the LMI and MMI response, the cytokine levels were significantly increased, as compared to control. Co-administration of melatonin along with propoxur significantly nullified the effect of the pesticide on the CMI response, except DTH and reversed levels of cytokines to near control/normal values. Thus, melatonin treatment considerably attenuated immunomodulation caused by sub-chronic treatment of propoxur in experimental animals.
Assuntos
Antioxidantes/farmacologia , Imunidade Celular/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Melatonina/farmacologia , Praguicidas/antagonistas & inibidores , Propoxur/antagonistas & inibidores , Administração Oral , Animais , Antioxidantes/administração & dosagem , Citocinas/imunologia , Citocinas/metabolismo , Hipersensibilidade Tardia/imunologia , Hipersensibilidade Tardia/metabolismo , Imunidade Celular/fisiologia , Leucócitos/imunologia , Leucócitos/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Melatonina/administração & dosagem , Praguicidas/imunologia , Glândula Pineal/química , Propoxur/imunologia , Ratos , Ratos Wistar , Fatores de Tempo , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Effect of melatonin in attenuation of propoxur induced oxidative stress and suppression of humoral immune response was studied in rats. Oral administration of propoxur (10 mg/kg) increased lipid peroxidation in serum after 28 days treatment. Superoxide dismutase, catalase and glutathione were also altered following propoxur exposure. In addition propoxur exposure markedly suppressed humoral immune response as assessed by antibody titre and plaque forming cell assay. Simultaneous treatment with melatonin (5 mg/kg, ip) markedly attenuated the effect of propoxur on (a) lipid peroxidation, (b) oxidative stress parameters and (c) immunotoxicity. Results have been discussed in the light of possible immunopotentiating and antioxidant effects of melatonin to understand the influence of oxidative stress on propoxur induced immunomodulation.
Assuntos
Formação de Anticorpos/efeitos dos fármacos , Formação de Anticorpos/imunologia , Imunossupressores/farmacologia , Melatonina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Propoxur/antagonistas & inibidores , Propoxur/farmacologia , Animais , Antioxidantes/metabolismo , Masculino , Malondialdeído/sangue , Ratos , Ratos WistarRESUMO
Kinetics analysis of K+ stimulated PNPPase was studied in the rat brain synaptosomes in the presence of propoxur. Non-competitive inhibition with respect to activation by PNPP was seen by the decreased maximal velocity (Vmax) without change in Michaelis-Menten Constant (Km). Activation energy values (delta E) were increased suggesting the decreased catalytic potential of the enzyme. It is also observed that dithiothrietol (DTT) (76 microM), cysteine (82 microM) and glutathione (120 microM) neutralized the inhibition of K(+)-PNPPase by propoxur to different extents.
