Efeito protetor do sesquiterpenóide β-Ionona na lesão gástrica induzida por etanol em camundongos : envolvimento da via NO/GMPc/KATP e da glutationa

Abstract

The β-ionone (4-[2,6,6-cyclohexene-1-trimetill]-3-butene-2-one) is a sesquiterpene (degraded terpenoid - C13) present in the molecular structure of retinol and β-carotene acid retinoic being formed from the mevalonate pathway in different types of plants. Research on the biological activities of β-ionone are still incipient and limited results with this compound are found in the literature. This study aims to investigate the activity of β-ionone in the model of ethanol-induced gastric injury. Handling of animals and experimental protocols were recorded by the Ethics Committee on Animal Research (CEPA) under number 87/2011. Swiss mice (n = 8), fasted 18 hours, were orally treated with BI at doses of 6.25, 12.5, 25, 50 and 100mg/kg. After 60 min of administration BI animals received 0.2 ml of absolute ethanol po. After 60 min this administration, the animals were sacrificed, the stomachs removed and analyzed to determine the rate of injury. Histologic examination of the stomach was performed by assigning scores to the parameters of edema, hemorrhage, loss of epithelial cells and inflammatory infiltrate. To investigate the role of mediators in BI effect, animals received indomethacin (10 mg / kg, po), L-NAME (20 mg / kg, ip) ODQ (10 mg / kg, ip), glibenclamide (5 mg / kg, ip) and capsazepine (5 mg / kg, ip) before treatment with BI (12.5 mg / kg, po). Misoprostol (50 mg / kg po), L-arginine (600 mg / kg, ip), diazoxide (3 mg / kg, ip) and capsaicin (0.3 mg / kg, po) was used positive pattern. The levels of nitrite and glutathione were measured in the stomach mucosa to investigate the effect of BI on the levels of NO and its antioxidant effect, respectively. Treatment of animals with the BI (12.5, 25, 50 and 100 mg / kg) reduced significantly and dose-dependent manner, the area of ethanol-induced gastric lesion to (11.41 ± 2.0, 7 92 * ± 1.8, 6.32 ± 2.0 and 1.43 ± 0.42% respectively). However, the BI lowest tested dose (6.25 mg / kg) showed no significant reduction of the ulcerated area (21.97 ± 1.8%). The administration of BI scores decreased hemorrhage, edema and loss of epithelial cells. The capsazepine and indomethacin were not able to reverse the protective effect of BI. Pretreatment of animals with L-NAME, ODQ and glibenclamide reversed the gastroprotective effect of BI, showing the involvement of NO and KATP channels in its mechanism of action. The group pretreated with BI (12.5 mg / kg po) showed a higher concentration of nitrite (24.18 mM) compared to the control group (17.68 mM). The pretreatment BI was effective in protecting against oxidative damage (346.4 ± 60.32 mg / g of tissue), preventing depletion of GSH levels in tissue. These results indicate that the β-ionone has gastroprotective effect in the model of ethanol-induced gastric injury mediated by the NO cGMP K ATP and terpene through the mediation of the GSH depletion induced by ethanol.