Background: Montelukast, a selective reversible cysteinyl leukotriene1 (CysLT1) receptor antagonist, is used in treatment of asthma, exercise induced-bronchospasm, allergic rhinitis and urticaria. It was shown to protect against cerebral ischemia/reperfusion injury. Objectives: To examine the possible anticonvulsant effect of montelukast, either alone or in combination with a known antiepileptic drug "valproate" against pentylenetetrazole (PTZ)-induced seizures. Methods: 112 adult male Swiss albino mice were used in the study and divided into two main groups, each containing 5 subgroups (Gp). The first main group "acute PTZ model (PTZ-a)" contains: Gp1 "vehicle-treated group" was injected with saline (10 ml/kg, intraperitoneally "i.p." in a single dose ), Gp2 "acute PTZ-control" injected with a single dose of PTZ (60 mg/kg, i.p.), Gp3 injected with valproate (50 mg/kg, i.p.) 30 minutes before PTZ, Gp4 injected with a single dose of montelukast (10 mg/kg, i.p.) 30 minutes before PTZ and Gp5 injected with both montelukast and valproate 30 minutes before PTZ administration. The second main group "kindling model (PTZ-k)" contains: Gp1 was injected with saline (i.p.) every other day for 17 days, Gp2 "PTZ-kindled control" received 9 PTZ injections in a dose of (40 mg/kg, i.p.) on alternate days for 17 days, Gp3 injected with valproate (50 mg/kg, i.p.) for 17 days, 30 minutes before PTZ, Gp4 daily injected with montelukast (10 mg/kg, i.p.) for 17 days 30 minutes before PTZ and Gp5 received both montelukast (10 mg/kg, i.p.) and valproate (50 mg/kg, i.p.) daily for 17 days, 30 minutes before administration of PTZ. Results: Single and repeated PTZ administration produced stage 4 seizures associated with a significant reduction in the brain level of reduced glutathione (GSH), concomittent with significant elevation in the brain levels of malondialdehyde (MDA), inteleukin1β (IL1β), tumor necrosis factor α (TNFα) and leukotriene D4 (LtD4). The use of valproate alone and its combination with montelukast suppressed the incidence of stage 4 seizures in acute PTZ induced convulsion while montelukast, valproate and their combination decreased the percentage of animals reaching stage 4 seizures in kindled mice. In both PTZ acute and kindled models, montelukast, valproate and their combined administration significantly elevated brain level of GSH and significantly decreased brain levels of MDA, IL1β, TNFα and LtD4 as compared to PTZ control groups. Interestingly, co-administration of valproate and montelukast resulted in a significant elevation in the brain level of GSH concomitant with a significant reduction in the brain levels of MDA, IL1β, TNFα and LtD4 as compared to each of the valproate and the montelukast groups in both models. Conclusion: Montelukast, either alone or in combination with valproate protects against PTZ induced seizures via blockade of leukotreine receptors & amelioration of oxidative stress and inflammatory cascades.

Background: Obesity induces bone related diseases as a consequence of reduced bone formation and unwarranted bone resorption. Therefore, the possible impact of adipokines on osteogenesis has been considered. Nevertheless, the osteogenic properties of omentin-1 are indistinct and contentious. The objective of the current work was to determine the regulatory effects of omentin-1 on bone turnover, along with exploring the fundamental molecular mechanisms in obese rats. Methods: The present study investigated the effects of intraperitoneal omentin-1 injection (8 μg/kg, once daily, for 14 days) in rats after feeding a high-fat diet for 10 weeks to induce obesity. Metabolic parameters and bone dry and ash weights were measured; serum calcium, phosphorus, alkaline phosphatase, and growth differentiation factor-11 (GDF-11), and femur histopathological changes were analyzed. Additionally, we investigated the effect of omentin-1 treatment on AMP protein-kinase (AMPK), mammalian target rapamycin (mTORC1) and nuclear receptor peroxisome proliferator-activated receptor-γ (PPAR-γ) expression. Results: The results revealed significant improvement in metabolic, bone biochemical parameters and histopathological changes in the omentin-1 treated group with a significant increase in area % of bone. A significant down-regulation of mTORC1 was identified through AMPK/mTORC1/PPAR-γ pathway accompanied by an increase in serum GDF-11.Conclusions: Omentin-1 can significantly promote bone health and viability via down-regulation of the AMPK/mTORC1/PPAR-γ signaling pathway and up-regulation of serum GDF-11, thus it can promote bone formation and prevent osteoporosis.

Background:The effect of vigorous exercise on testicular function is poorly understood. This work aims to identify the resveratrol influence on the altered reproductive function induced by forced exercise and to screen the relevant possible mechanisms. Methods: The study comprised control, forced exercise (FE), and resveratrol treatment groups carried out on a total of 24 adult male rats. After 8 weeks of the exercise, the pituitary and testicular hormones, corticosterone, tumor necrosis factor (TNF-α), IL-6, epididymal sperm parameters, testicular oxidantantioxidant markers, testicular ornithine decarboxylase (ODC) activity, polyamines, testicular histopathology, and immunohistochemistry for apoptotic reactions were all measured. Results: The FE group showed significant reductions in the pituitary and testicular hormones, sperm count, and motility, while corticosterone, TNFα, IL-6 serum levels, and aberrant forms of sperms were significantly increased. Testicular tissue displayed abnormal architecture, apoptotic changes with a significantly increased malondialdehyde level, ODC activity and polyamines, and a reduction in superoxide dismutase activity. In comparison to the FE group, administration of resveratrol significantly improved the gonadal hormones, corticosterone, TNF-α, IL-6 levels, sperm parameters, oxidant-antioxidant system, ODC activity, and polyamines with an enhancement of testicular architecture and apoptosis. Conclusion: Resveratrol was effective in attenuating testicular dysfunction caused by forced swimming exercise in rats.

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