Background/Aims There are increasing evidences for gastrointestinal motility disorder (GIMD) and gastric stress ulcer induced by noise stress. The present study was to investigate the reversed effect of melatonin on GIMD and gastric stress ulcer induced by noise stress and potential mechanism. Methods Noise stress was induced on rats, and melatonin (15 mg/kg) was administered to rats by intraperitoneal injection. Differences were assessed in gastric residual rate (GRR), small intestine propulsion rate (SPR), Guth injury score, cortisol, gastrointestinal hormones (calcitonin-gene-related peptide and motilin) and oxidative stress markers (superoxide dismutase and malondialde hyde) in blood plasma as well as gastric mucosa homogenate with or without melatonin. The pathological examination of gastric mucosa was also performed. Results The GRR and SPR were improved by noise stress compared with control ( P < 0.05). The pathological examination and Guth injury score revealed gastric stress ulcer. Moreover, the levels of cortisol, motilin and malondialdehyde in blood plasma and malondialdehyde in gastric mucosa homogenate were increased by noise stress ( P < 0.05). CGRP and superoxide dismutase activity in both of blood plasma and gastric mucosa homogenate were significantly decreased ( P < 0.05). Furthermore, melatonin reversed changes in GRR, SPR, pathological examination, Guth injury score, cortisol, motilin, CGRP, superoxide dismutase activity and malondialdehyde ( P < 0.05). Conclusions Melatonin is effective in reversing the GIMD and gastric stress ulcer induced by noise stress. The underlying mechanism may be involved in oxidative stress and gastrointestinal hormones.

Background/Aims: Angiotensin II type I receptor agonistic autoantibody (AT1-AA) is closely related to pre-eclampsia, which is characterized by proteinuria and hypertension. AT1-AA has been shown to enhance the effect of AngII in pre-eclampsia, such as production of endothelin-1, activation of ROS, and vasoconstriction, which are considered to be associated with hypertension; however, whether or not AT1-AA participates in podocyte damage leading to the generation of proteinuria has not been reported. In this study we investigated the role of pre-eclamptic serum AT1-AA on podocytes and the mechanism underlying the generation of proteinuria. Methods: The levels of AT1-AA isolated from pre-eclamptic sera were determined by an enzyme-linked immunosorbent assay. Human podocytes were cultured in vitro and treated with various concentrations of AT1-AA. Whether or not an ERK1/2 inhibitor and TRPC6 siRNA inhibit the effect of AT1-AA on podocytes was determined. Western blot was used to detect the expression of podocyte-specific proteins (nephrin, synaptopodin, and podocin) and the phosphorylation of ERK1/2 and TRPC6. The arrangement of F-actin was observed by immunofluorescence. A Calcineurin Cellular Activity Assay Kit was used to detect calcineurin activity. Changes in the intracellular Ca²⁺ concentration was determined by confocal laser. Results: AT1-AA induced a decrease in podocyte-specific protein expression and calcineurin activity and increased expression of p-ERK1/2 and TRPC6 protein and the intracellular Ca²⁺ concentration. Immunofluorescence revealed rearrangement of F-actin. PD98059, an inhibitor of ERK1/2, and TRPC6 siRNA attenuated the decreased expression of podocyte-specific proteins and decreased intracellular Ca²⁺ concentration. The expression of TRPC6 was reduced following the addition of ERK1/2 inhibitor. Conclusion: AT1-AA induced podocyte damage in a dose-dependent manner. The underlying mechanism might involve activation of the TRPC6 –calcium/calcineurin pathway. This study provides new details regarding podocyte injury and the mechanism underlying the generation of proteinuria in pre-eclampsia.

No abstract