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The anti-catabolic bisphosphonate alendronate is considered as the first-line medical treatment in post-menopausal osteoporosis; but several side effects, including gastric mucosal injury, are associated with its use. The aim was to elucidate whether combined treatment with melatonin plus alendronate would be more advantageous in the maintenance of bone and the prevention of gastric side effects. Under anaesthesia, female Sprague-Dawley rats underwent bilateral ovariectomy (OVX), while control group had sham surgery. Four weeks after the surgery, OVX rats were treated with saline, melatonin (25 μg/mL/d), alendronate (70 μg/kg/wk), melatonin + alendronate, melatonin + melatonin receptor antagonist (luzindole, 10 μg/kg/d) or alendronate + melatonin + luzindole for 8 weeks. Rats were euthanized at the end of 12th week. Runx2 expression, apoptotic cells, and trabecular thickness were evaluated in tibiae, while gastric tissues were analysed for oxidative injury parameters. In all OVX groups, Runx2 expression was depressed. Saline-treated OVX group presented an extreme decrease in calcified area in opposition to melatonin-or alendronate-treated groups, while the bones in alendronate + melatonin-treated group were similar to those of the sham-operated group. Concomitant with the improvements examined histologically in bone tissues, quantitative TUNEL (+) cells were similarly lower in alendronate-or melatonin-treated groups. Oxidative gastric damage was increased in saline-or alendronate-treated groups, which were depressed in the presence of melatonin. Although melatonin and alendronate exerted similar supportive effects on the maintenance of bone mass, melatonin may have a more advantageous impact by protecting against OVX-induced gastric injury, which was aggravated by alendronate use. Highlights:Our results demonstrate that alendronate and melatonin had similar supportive effects on the maintenance of bone mass, while melatonin prevented the gastric side effects of alendronate, making this combination an advisable therapeutic approach in the treatment of menopausal osteoporosis.

Low-calorie sweeteners are considered to be beneficial in calorie control, but the impact of these sweeteners on gastric emptying is not well described. The purpose of this study was to compare the gastric emptying rate of agave nectar with those of glucose and fructose, and to evaluate the interaction of cholecystokinin (CCK)-1, CCK-2 and glucagon-like peptide-1 (GLP-1) receptors in agave-induced alterations in gastric emptying. Female Sprague-Dawley rats were fitted with gastric cannulas. Following the recovery, the gastric emptying rates of glucose, fructose and agave at 12.5%, 15% or 50% concentrations were measured and compared with that of saline. GLP-1 receptor antagonist exendin fragment 9-39 (30 μg kg), CCK-1 receptor antagonist devazepide (1 mg kg) or gastrin/CCK-2 receptor antagonist YM022 (1 mg kg) was injected subcutaneously 1 min before the emptying of glucose, fructose or agave at their 50% concentrations. When compared with saline emptying, gastric emptying of glucose was significantly delayed at its 25% and 50% concentrations, but the emptying of 12.5% glucose was not different from that of saline. Agave emptying, which was delayed with respect to saline emptying, was not altered by CCK-1 receptor blockade; but agave emptied from the stomach as rapidly as saline following the blockade of either CCK-2 or GLP-1 receptors. The findings demonstrate that the inhibitory effect of agave on gastric emptying is mediated by both CCK-2 and GLP-1 receptors, suggesting that natural sweeteners including agave may have satiating effects through the inhibition of gastric motility via enteroendocrine mechanisms.

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Purpose: To evaluate the effects of M. quinquenervia extract on ethanol-induced peptic ulcer in rats. Methods: The following three groups of (n = 6) Sprague Dawley rats were included in this study: vehicle (C), ethanol-administered (E) and ethanol + M. quinquenervia-treated (MQ). MQ group rats received 100 μg/mL M. quinquenervia essential oil just before 96 % ethanol induction (1 ml/kg). One hour after ulcer induction, the animals were euthanized, and gastric and duodenal tissues were removed. Tissue samples were analysed for myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO) activity, malondialdehyde (MDA) and glutathione (GSH) levels, and histopathological examinations were performed by light microscopy. Results: Gastric and duodenal GSH levels that decreased in the ethanol-administered ulcer groups (p < 0.001), rose following MQ treatment (p < 0.5). Moreover, elevated MPO and MDA levels (p < 0.5) in gastric tissues decreased after MQ-treatment. Similarly, the MQ-treated group showed recovery and control-like morphology compared to the ethanol group in both gastric and duodenal tissues when examined by microscopy. Conclusion: The results indicate that M. quinquenervia extract has a positive impact on gastric injury in rats due to its antioxidant activity. Thus, the plant has a potential for the clinical management of gastric ulcer.