RESUMO
The intestinal Ca²âº absorption is inhibited by menadione (MEN) through oxidative stress and apoptosis. The aim of this study was to elucidate whether the antioxidant and antiapoptotic properties of melatonin (MEL) could protect the gut against the oxidant MEN. For this purpose, 4-week-old chicks were divided into four groups: (1) controls, (2) treated i.p. with MEN (2.5 µmol/kg of b.w.), (3) treated i.p. with MEL (10 mg/kg of b.w.), and (4) treated with 10 mg MEL/kg of b.w after 2.5 µmol MEN/kg of b.w. Oxidative stress was assessed by determination of glutathione (GSH) and protein carbonyl contents as well as antioxidant enzyme activities. Apoptosis was assayed by the TUNEL technique, protein expression, and activity of caspase 3. The data show that MEL restores the intestinal Ca²âº absorption altered by MEN. In addition, MEL reversed the effects caused by MEN such as decrease in GSH levels, increase in the carbonyl content, alteration in mitochondrial membrane permeability, and enhancement of superoxide dismutase and catalase activities. Apoptosis triggered by MEN in the intestinal cells was arrested by MEL, as indicated by normalization of the mitochondrial membrane permeability, caspase 3 activity, and DNA fragmentation. In conclusion, MEL reverses the inhibition of intestinal Ca²âº absorption produced by MEN counteracting oxidative stress and apoptosis. These findings suggest that MEL could be a potential drug of choice for the reversal of impaired intestinal Ca²âº absorption in certain gut disorders that occur with oxidative stress and apoptosis.
Assuntos
Antioxidantes/farmacologia , Apoptose , Cálcio/metabolismo , Absorção Intestinal/efeitos dos fármacos , Melatonina/farmacologia , Vitamina K 3/farmacologia , Animais , Antioxidantes/fisiologia , Proteínas Aviárias/metabolismo , Caspase 3/metabolismo , Células Cultivadas , Galinhas , Duodeno/efeitos dos fármacos , Duodeno/metabolismo , Enterócitos/metabolismo , Glutationa/metabolismo , Melatonina/fisiologia , Dilatação Mitocondrial , Estresse Oxidativo , Carbonilação ProteicaRESUMO
This review summarizes the metabolism, secretion, regulation and sites of action of melatonin. An updated description of the melatonin receptors, including their signal transduction mechanisms, distribution and characterization of receptor genes, is given. Special emphasis is focused on the clinical aspects and potential uses of melatonin in the sleep-wake rhythms, in the immune function, in cancer therapy, in neuroprotection against oxidative damage and antioxidant activities in different tissues. Finally, combined effects of melatonin with other drugs are discussed.
