We investigated the effect of resveratrol on oxidation damage and variation of antioxidant defences induced by 2-nitropropane (2-NP) in rat liver. One group of five rats was given resveratrol (50 mg/kg/d body weight) ...We investigated the effect of resveratrol on oxidation damage and variation of antioxidant defences induced by 2-nitropropane (2-NP) in rat liver. One group of five rats was given resveratrol (50 mg/kg/d body weight) in the diet until the end of the experiment. After 14 days, 2-NP (100 mg/kg) was injected i.p. into two groups of animals (2-NP + Res and 2-NP groups) while control animals were treated with vehicle alone. Animals were killed by decapitation 15 h after 2-NP injection. The levels of 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodGuo) were significantly increased by 2-NP injection, but resveratrol restored 8-oxodGuo to levels similar to those measured in controls. Superoxide dismutase (SOD) and xanthine oxidase (XO) activities in the liver were significantly increased by 2-NP, but were similar to those found in the group treated with resveratrol and 2-NP (2-NP + Res). We also observed that 2-NP injection significantly reduced GSH/GSSG ratio in the liver and this change was partially reversed by resveratrol treatment. Moreover, an increased (p = 0.06) expression of the oxoguanine glycosylase (OGG1) gene was found in 2-NP rats, whereas pre-treatment with resveratrol restored OGG1 expression to control levels. An up-regulation of caspase-3 was also observed in 2-NP group, but resveratrol significantly reduced the activation of caspase-3. An inverse correlation was found between GSH/GSSG and 8-oxodGuo in the 2-NP group. On the contrary, 8-oxodGuo levels, GSH/GSSG ratio, XO and SOD activities in the colon mucosa of 2-NP rats were similar to those of controls confirming that the colon is not a target of oxidation damage 2-NP induced. In conclusion, our results indicate that oxidative DNA damage and apoptosis are the main mechanisms of cell death in a model of chemically induced severe acute hepatic injury and in this early stage of damage pharmacological doses of resveratrol can ameliorate hepatic oxidation damage by its antioxidant and scavenging properties through a reduction of XO activity, a partial restoration of GSH/GSSG ratio in addition to its capacity to inhibit apoptosis.展开更多
2-硝基-2-苄基-1,3-丙二醇是合成药物中间体α-丝氨酸的重要先行体,它由β-硝基苯乙烷与三聚甲醛在碱催化条件下的羟醛缩合反应合成。产物通过重结晶得到无色透明晶体,产率49.01%。对去质子剂、反应物配料比、反应温度以及反应时间进行...2-硝基-2-苄基-1,3-丙二醇是合成药物中间体α-丝氨酸的重要先行体,它由β-硝基苯乙烷与三聚甲醛在碱催化条件下的羟醛缩合反应合成。产物通过重结晶得到无色透明晶体,产率49.01%。对去质子剂、反应物配料比、反应温度以及反应时间进行了优化。产物的结构通过1 H NMR,13CNMR,IR表征。X-Ray单晶衍射分析揭示分子间和分子内氢键的存在。展开更多
文摘We investigated the effect of resveratrol on oxidation damage and variation of antioxidant defences induced by 2-nitropropane (2-NP) in rat liver. One group of five rats was given resveratrol (50 mg/kg/d body weight) in the diet until the end of the experiment. After 14 days, 2-NP (100 mg/kg) was injected i.p. into two groups of animals (2-NP + Res and 2-NP groups) while control animals were treated with vehicle alone. Animals were killed by decapitation 15 h after 2-NP injection. The levels of 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodGuo) were significantly increased by 2-NP injection, but resveratrol restored 8-oxodGuo to levels similar to those measured in controls. Superoxide dismutase (SOD) and xanthine oxidase (XO) activities in the liver were significantly increased by 2-NP, but were similar to those found in the group treated with resveratrol and 2-NP (2-NP + Res). We also observed that 2-NP injection significantly reduced GSH/GSSG ratio in the liver and this change was partially reversed by resveratrol treatment. Moreover, an increased (p = 0.06) expression of the oxoguanine glycosylase (OGG1) gene was found in 2-NP rats, whereas pre-treatment with resveratrol restored OGG1 expression to control levels. An up-regulation of caspase-3 was also observed in 2-NP group, but resveratrol significantly reduced the activation of caspase-3. An inverse correlation was found between GSH/GSSG and 8-oxodGuo in the 2-NP group. On the contrary, 8-oxodGuo levels, GSH/GSSG ratio, XO and SOD activities in the colon mucosa of 2-NP rats were similar to those of controls confirming that the colon is not a target of oxidation damage 2-NP induced. In conclusion, our results indicate that oxidative DNA damage and apoptosis are the main mechanisms of cell death in a model of chemically induced severe acute hepatic injury and in this early stage of damage pharmacological doses of resveratrol can ameliorate hepatic oxidation damage by its antioxidant and scavenging properties through a reduction of XO activity, a partial restoration of GSH/GSSG ratio in addition to its capacity to inhibit apoptosis.
文摘2-硝基-2-苄基-1,3-丙二醇是合成药物中间体α-丝氨酸的重要先行体,它由β-硝基苯乙烷与三聚甲醛在碱催化条件下的羟醛缩合反应合成。产物通过重结晶得到无色透明晶体,产率49.01%。对去质子剂、反应物配料比、反应温度以及反应时间进行了优化。产物的结构通过1 H NMR,13CNMR,IR表征。X-Ray单晶衍射分析揭示分子间和分子内氢键的存在。
