Remote ischemic preconditioning-induced late cardioprotection: possible role of melatonin-mitoKATP-H2S signaling pathway.

PURPOSE: Remote ischemic preconditioning (RIPC) confers cardioprotection against ischemia reperfusion (IR) injury. However, the precise mechanisms involved in RIPC-induced cardioprotection are not fully explored. The present study was aimed to identify the role of melatonin in RIPC-induced late cardioprotective effects in rats and to explore the role of H2S, TNF-α and mitoKATP in melatonin-mediated effects in RIPC. METHODS: Wistar rats were subjected to RIPC in which hind limb was subjected to four alternate cycles of ischemia and reperfusion of 5 min duration by using a neonatal blood pressure cuff. After 24 h of RIPC or ramelteon-induced pharmacological preconditioning, hearts were isolated and subjected to IR injury on the Langendorff apparatus. RESULTS: RIPC and ramelteon preconditioning protected the hearts from IR injury and it was assessed by a decrease in LDH-1, cTnT and increase in left ventricular developed pressure (LVDP). RIPC increased the melatonin levels (in plasma), H2S (in heart) and decreased TNF-α levels. The effects of RIPC were abolished in the presence of melatonin receptor blocker (luzindole), ganglionic blocker (hexamethonium) and mitochondrial KATP blocker (5-hydroxydecanoic acid). CONCLUSIONS: RIPC produce delayed cardioprotection against IR injury through the activation of neuronal pathway, which may increase the plasma melatonin levels to activate the cardioprotective signaling pathway involving the opening of mitochondrial KATP channels, decrease in TNF-α production and increase in H2S levels. Ramelteon-induced pharmacological preconditioning may also activate the cardioprotective signaling pathway involving the opening of mitochondrial KATP channels, decrease in TNF-α production and increase in H2S levels.

Remote ischemic preconditioning-induced late cardioprotection: possible role of melatonin-mitoKATP-H2S signaling pathway

Purpose: Remote ischemic preconditioning (RIPC) confers cardioprotection against ischemia reperfusion (IR) injury. However, the precise mechanisms involved in RIPC-induced cardioprotection are not fully explored. The present study was aimed to identify the role of melatonin in RIPC-induced late cardioprotective effects in rats and to explore the role of H2 S, TNF-α and mitoKATP in melatoninmediated effects in RIPC. Methods: Wistar rats were subjected to RIPC in which hind limb was subjected to four alternate cycles of ischemia and reperfusion of 5 min duration by using a neonatal blood pressure cuff. After 24 h of RIPC or ramelteon-induced pharmacological preconditioning, hearts were isolated and subjected to IR injury on the Langendorff apparatus. Results: RIPC and ramelteon preconditioning protected the hearts from IR injury and it was assessed by a decrease in LDH-1, cTnT and increase in left ventricular developed pressure (LVDP). RIPC increased the melatonin levels (in plasma), H2 S (in heart) and decreased TNF-α levels. The effects of RIPC were abolished in the presence of melatonin receptor blocker (luzindole), ganglionic blocker (hexamethonium) and mitochondrial KATP blocker (5-hydroxydecanoic acid). Conclusion: RIPC produce delayed cardioprotection against IR injury through the activation of neuronal pathway, which may increase the plasma melatonin levels to activate the cardioprotective signaling pathway involving the opening of mitochondrial KATP channels, decrease in TNF-α production and increase in H2 S levels. Ramelteon-induced pharmacological preconditioning may also activate the cardioprotective signaling pathway involving the opening of mitochondrial KATP channels, decrease in TNF-α production and increase in H2 S levels.

Antitumor activity and safety evaluation of nanaparticle-based delivery of quercetin through intravenous administration in mice.

The present study focused on the inhibition effects and the safety evaluation of the quercetin when it was loaded into the nanoliposomes on cervical cancer in vitro and in vivo. Quercetin loaded nanoliposomes (Que-NLs) were first prepared by thin film hydration method and the characterizations of Que-NLs were measured with TEM and dynamic light scattering (DLS) techniques. Then the anti-cervical cancer efficiencies were evaluated by MTT and U14 tumor-bearing mice models in vitro and in vivo respectively. The body changes, organ index, biochemical criterions and histopathological of livers and kidneys in tumor-bearing mice were further assayed to evaluate the safety of Que-NLs. In vitro results showed that Que-NLs have a low IC50 value compared with free-Que, thus leading to the stronger antitumor efficacy to Hela cells. In vivo results further demonstrated that the Que-NLs display a higher inhibition effect on U14 cervical cancer compared with free-Que caused no obvious hepatic toxicity or kidney dysfunction in Balb/c mice. So we concluded that Que-NLs possess effective anti-cervical cancer properties and does not exhibit the notable adverse effects associated with cervical cancer.

Prescription consisting of Vitamin C and Baicalin inhibits tumor growth by enhancing the antioxidant capacity in vivo.

PURPOSE: To explore the antitumor effect of prescription consisting of Vitamin C (Vc) and Baicalin (PVB). METHODS: To explore the antitumor effect of PVB, using U14 cervical tumor-bearing mice model was used and the drugs were administrated through the gavages. Spectrophotometry was used to determine the content of superoxide dismutase (SOD), malondialdehyde (MDA) and cytokines IL-2, Il-4 and IFN-γ. RESULTS: PVB had a better antitumor effect than baicalin and Vc used alone with an inhibition rate of 58.18% (p<0.05); PVB significantly improved the spleen index (p<0.01), and significantly reduced MDA content (p<0.01) but increased SOD activity in liver tissue and serum (p<0.01). CONCLUSIONS: PVB shows better antitumor effect than Vc and baicalin used alone, and it can significantly enhance the immunity and antioxidant capacity of the mice.