Background/Aims: Prior studies demonstrate that hypoxia inducible factor subtype 1α (HIF-1α) in retinal tissues is involved in development of diabetic retinopathy (DR). In this report, we particularly examined the role played by mammalian target of rapamycin (mTOR) in regulating expression of HIF-1α and its downstream pathway, namely vascular endothelial growth factor (VEGF). Methods: Streptozotocin (STZ) was systemically injected to induce hyperglycemia in rats. ELISA and Western Blot analysis were employed to determine the levels of HIF-1α and VEGF as well as expression of mTOR pathways in retinal tissues of control rats and STZ rats. Results: Our results show that HIF-1α and VEGF as well as VEGF receptor subtype 2 (VEGFR-2) were increased in STZ rats. Also, the protein expression of p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4 (4E-BP1), p70 ribosomal S6 protein kinase 1 (S6K1) pathways were amplified in diabetic retina compared with controls. Blocking mTOR by using rapamycin significantly attenuated activities of HIF-1α and VEGF signaling pathways. Conclusion: Our data for the first time revealed specific signaling pathways engaged in the development of DR, including the activation of mTOR and HIF-1α -VEGF mechanism. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of DR often observed in clinics.

Objective This study was conducted to investigate the protective effect of melatonin against aflatoxin B1 (AFB1) cardiotoxicity by evaluating NOD-like receptor family pyrin domain containing protein 3 (NLRP3) signalling. Methods Four groups of five rats each were assessed: control group (vehicle only), two AFB1 (0.15 and 0.3 mg/kg)-treated groups, and a combined AFB1 (0.3 mg/kg) plus melatonin (5 mg/kg)-treated group. After 6 weeks of once-daily intragastric treatment, cardiac pathologic changes were observed under optical microscopy, and oxidative/antioxidative parameters were measured in myocardial homogenate. Cardiac tissue expression of NLRP3 and other important inflammasome components was also analysed. Results Compared with controls, increasing concentrations of AFB1 were associated with increased oxidative stress and caused myocardial structure damage. In addition, AFB1 dose-dependently activated the NLRP3 signalling pathway. All these indices were significantly ameliorated by combined AFB1 plus melatonin treatment versus high-dose AFB1 alone. Conclusion Melatonin may reduce NLRP3 inflammasome activation by inhibiting oxidative stress and thus protect against injury from AFB1-induced myocardial toxicity.

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