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
OBJECTIVE:To investigate the efficacy of Fig fruit powder and olive on hepatic,renal and splenic injury induced by 2-nitropropane(2-NP)in mice,especially if they were used in combination.METHODS:A total of 40 adult BA...OBJECTIVE:To investigate the efficacy of Fig fruit powder and olive on hepatic,renal and splenic injury induced by 2-nitropropane(2-NP)in mice,especially if they were used in combination.METHODS:A total of 40 adult BALB/c male mice weighting 25-30 g/each.Mice were categorized into five groups(8 each).Group 1 as negative control.Group 2 as positive control group intraperitoneally injected with 2-NP(100 mg/kg b.w.)3 times/weekly for eight weeks.Group 3 injected with 2-NP and were orally supplemented with Fig(300 mg/kg).Group 4 injected with 2-NP and were orally supplemented with olive(100 mg/kg).Group 5 injected with 2-NP and were orally supplemented with mixture of Fig and olive(3∶1 respectively).RESULTS:Histopathological observation of liver in mice treated with 2-NP showed cellular degeneration,pyknosis,and congestion of the portal vein.In kidney there were disorganization of the cortical tissues,cellular necrosis and plenty of inflammatory lymphocytic aggregation.Significant elevations in liver function parameters(alanine aminotransferase and aspartate aminotransferase),m RNA expression levels of tumor necrosis factor-α,nicotinamide adenine dinucleotide phosphate oxidase and cyclooxygenase were detected as anti-inflammatory markers and 5-lipoxygenase,interleukin-1βand interleukin-6 as inflammatory biomarkers for liver and spleen,also significant elevations was detected in lipid peroxidation levels.The levels of antioxidants,glutathione,glutathione peroxidase,catalase and superoxide dismutase were significantly decreased.CONCLUSION:our findings indicated that Fig fruit powder and olive protected against hepatic,renal and splenic injury induced with 2-NP in mice,especially if they were used in combination.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OBJECTIVE:To investigate the efficacy of Fig fruit powder and olive on hepatic,renal and splenic injury induced by 2-nitropropane(2-NP)in mice,especially if they were used in combination.METHODS:A total of 40 adult BALB/c male mice weighting 25-30 g/each.Mice were categorized into five groups(8 each).Group 1 as negative control.Group 2 as positive control group intraperitoneally injected with 2-NP(100 mg/kg b.w.)3 times/weekly for eight weeks.Group 3 injected with 2-NP and were orally supplemented with Fig(300 mg/kg).Group 4 injected with 2-NP and were orally supplemented with olive(100 mg/kg).Group 5 injected with 2-NP and were orally supplemented with mixture of Fig and olive(3∶1 respectively).RESULTS:Histopathological observation of liver in mice treated with 2-NP showed cellular degeneration,pyknosis,and congestion of the portal vein.In kidney there were disorganization of the cortical tissues,cellular necrosis and plenty of inflammatory lymphocytic aggregation.Significant elevations in liver function parameters(alanine aminotransferase and aspartate aminotransferase),m RNA expression levels of tumor necrosis factor-α,nicotinamide adenine dinucleotide phosphate oxidase and cyclooxygenase were detected as anti-inflammatory markers and 5-lipoxygenase,interleukin-1βand interleukin-6 as inflammatory biomarkers for liver and spleen,also significant elevations was detected in lipid peroxidation levels.The levels of antioxidants,glutathione,glutathione peroxidase,catalase and superoxide dismutase were significantly decreased.CONCLUSION:our findings indicated that Fig fruit powder and olive protected against hepatic,renal and splenic injury induced with 2-NP in mice,especially if they were used in combination.