Antioxidant and antiapoptotic properties of melatonin restore intestinal calcium absorption altered by menadione.
The intestinal Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ absorption in certain gut disorders that occur with oxidative stress and apoptosis.
A
A
Carpentieri
A
A
Marchionatti
V
V
Areco
A
A
Perez
V
V
Centeno
N
N
Tolosa de Talamoni
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000502:physiology; D017209:Apoptosis; D030161:Avian Proteins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D002645:Chickens; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D020895:Enterocytes / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects*; D008550:Melatonin / Q000494:pharmacology* / Q000502:physiology; D008933:Mitochondrial Swelling; D018384:Oxidative Stress; D050050:Protein Carbonylation; D024483:Vitamin K 3 / Q000494:pharmacology*
D000975:Antioxidants; D030161:Avian Proteins; D024483:Vitamin K 3; D053148:Caspase 3; D005978:Glutathione; D008550:Melatonin; D002118:Calcium