Ischemia/reperfusion(I/R) is a pathological process that occurs in numerous organs throughout the human body, and it is frequently associated with severe cellular damage and death. Recently it has emerged that ferropt...Ischemia/reperfusion(I/R) is a pathological process that occurs in numerous organs throughout the human body, and it is frequently associated with severe cellular damage and death. Recently it has emerged that ferroptosis, a new form of regulated cell death that is caused by iron-dependent lipid peroxidation, plays a significantly detrimental role in many I/R models. In this review, we aim to revise the pathological process of I/R and then explore the molecular pathogenesis of ferroptosis. Furthermore,we aim to evaluate the role that ferroptosis plays in I/R, providing evidence to support the targeting of ferroptosis in the I/R pathway may present as a therapeutic intervention to alleviate ischemia/reperfusion injury(IRI) associated cell damage and death.展开更多
Orientin is a flavonoid monomer.In recent years,its importance as a source of pharmacological active substance is growing rapidly due to its properties such as anti-myocardial ischemia,anti-apoptosis,anti-radiation,an...Orientin is a flavonoid monomer.In recent years,its importance as a source of pharmacological active substance is growing rapidly due to its properties such as anti-myocardial ischemia,anti-apoptosis,anti-radiation,anti-tumor,and anti-aging.However,the neuroprotective effects of Orientin on stroke injury have not been comprehensively evaluated.The aim of the present study was thus to investigate the neuroprotective capacity and the potential mechanisms of Cyperus esculentus L.orientin(CLO)from Cyperus esculentus L.leaves against ischemia/reperfusion(I/R)injury using standard orientin as control.For in vitro studies,we treated HT22 cells with CoCl2 as an in vitro ischemic injury model.HT22 cells in the control group were treated with CoCl2.For in vivo studies,we used rat models of middle cerebral artery occlusion,and animals that received sham surgery were used as controls.We found that CLO protected CoCl2-induced HT22 cells against ischemia/reperfusion injury by lowering lipid peroxidation and reactive oxygen species formation as well as decreasing protein oxidation.However,CLO did not reduce the release of lactate dehydrogenase nor increase the activity of superoxide dismutase.Results showed that CLO could decrease neurological deficit score,attenuate brain water content,and reduce cerebral infarct volume,leading to neuroprotection during cerebral ischemia-reperfusion injury.Our studies indicate that CLO flavonoids can be taken as a natural antioxidant and bacteriostastic substance in food and pharmaceutical industry.The molecular mechanisms of CLO could be at least partially attributed to the antioxidant properties and subsequently inhibiting activation of casepase-3.All experimental procedures and protocols were approved on May 16,2016 by the Experimental Animal Ethics Committee of Xinjiang Medical University of China(approval No.IACUC20160516-57).展开更多
AIM: To investigate the protective effect of lansoprazoleon ischemia and reperfusion (I/R)-induced rat intestinalmucosal injury in vivo.METHODS: Intestinal damage was induced by clampingboth the superior mesenteric ar...AIM: To investigate the protective effect of lansoprazoleon ischemia and reperfusion (I/R)-induced rat intestinalmucosal injury in vivo.METHODS: Intestinal damage was induced by clampingboth the superior mesenteric artery and the celiac trunkfor 30 rain followed by reperfusion in male Sprague-Dawleyrats. lansoprazole was given to rats intraperitoneally 1 hbefore vascular clamping.RESULTS: Both the intraluminal hemoglobin and proteinlevels, as indices of mucosal damage, significantlyincreased in I/R-groups comparion with those of sham-operation groups. These increases in intraluminal hemoglobinand protein levels were significantly inhibited by the treatmentwith lansoprazole at a dose of 1 mg/kg. Small intestineexposed to I/R resulted in mucosal inflammation that wascharacterized by significant increases in thiobarbituric acid-reactive substances (TBARS), tissue-associatedmyeloperoxidase activity (MPO), and mucosal content of ratcytokine-induced neutrophil chemoattractant-1 (CINC-1).These increases in TBARS, MPO activities and CINC-1 contentin the intestinal mucosa after I/R were all inhibited bypretreatment with lansoprazole at a dose of 1 mg/kg.Furthermore, the CINC-1 mRNA expression was increasedduring intestinal I/R, and this increase in mRNA expressionwas inhibited by treatment with lansoprazole.CONCLUSION: Lansoprazole inhibits lipid peroxidation andreduces development of intestinal mucosal inflammationinduced by I/R in rats, suggesting that lansoprazole mayhave a therapeutic potential for I/R injury.展开更多
AIM： To compare different preconditioning strategies to protect the liver from ischemia/reperfusion injury focusing on the expression of pro- and anti-apoptotic proteins. Interventions comprised different modes of is...AIM： To compare different preconditioning strategies to protect the liver from ischemia/reperfusion injury focusing on the expression of pro- and anti-apoptotic proteins. Interventions comprised different modes of ischemic preconditioning （IP） as well as pharmacologic pretreatment by α-lipoic acid （LA）. METHODS： Several groups of rats were compared： sham operated animals, non-pretreated animals （nt）, animals receiving IP （10 rain of ischemia by clamping of the portal triad and 10 min of reperfusion） prior to sustained ischemia, animals receiving selective ischemic preconditioning （IPsel, 10 min of ischemia by selective clamping of the ischemic lobe and 10 rain of reperfusion） prior to sustained ichemia, and animals receiving 500 1μmol α-LA injected i.v. 15 min prior to the induction of 90 min of selective ischemia. RESULTS： Cellular damage was decreased only in the LA group. TUNEL-positive hepatocytes as well as necrotic hepatocyte injury were also decreased only by LA（19 ± 2 vs 10 ± 1, P〈 0.05 and 29 ± 5 vs 12 ± 1, P 〈 0.05）. Whereas caspase 3- activities in liver tissue were unchanged, caspase 9- activity in liver tissue was decreased only by LA pretreatment （3.1 ± 0.3 vs 1.8 ± 0.2, P 〈 0.05）. Survival rate as the endpoint of liver function was increased after IP and LA pretreatment but not after IPsel. Levels of lipid peroxidation （LPO） in liver tissue were decreased in the IP as well as in the LA group compared to the nt group. Determination of pro- and anti-apoptotic proteins showed a shift towards anti-apoptotic proteins by LA. In contrast, both our IP strategies failed to influence apototic cell death. CONCLUSION： IP, consisting of 10 min of ischemia and 10 min of reperfusion, ischemia/reperfusion injury protects only partly against of the liver prior to 90 min of selective ischemia. IPsel did not influence ischemic tolerance of the liver. LA improved tolerance to ischemia, possibly by downregulation of pro-apoptotic Bax.展开更多
Objective To investigate the possible protection provided by oral quercetin pretreatment against hepatic ischemia-reperfusion injury in rats. Methods The quercetin （0.13 mmol/kg） was orally administrated in 50 min p...Objective To investigate the possible protection provided by oral quercetin pretreatment against hepatic ischemia-reperfusion injury in rats. Methods The quercetin （0.13 mmol/kg） was orally administrated in 50 min prior to hepatic ischemia-reperfusion injury. Ascorbic acid was also similarly administered. The hepatic content of quercetin was assayed by high performance liquid chromatography （HPLC）. Plasma glutamic pyruvic transaminase （GPT）, glutamic oxaloacetic transaminase （GOT） activities and malondialdehyde （MDA） concentration were measured as markers of hepatic ischemia-reperfusion injury. Meanwhile, hepatic content of glutathione （GSH）, activities of superoxide dismutase （SOD）, glutathione peroxidase （GSH-Px） and xanthine oxidase （XO）, total antioxidant capacity （TAOC）, contents of reactive oxygen species （ROS） and MDA, DNA fragmentation were also determined. Results Hepatic content of quercetin after intragastric administration of quercetin was increased significantly. The increases in plasma GPT展开更多
Testicular torsion （TT） is a serious urologic emergency that is observed in adolescent males and that can lead to infertility if left untreated. The ischemia-reperfusion （I/R） injury due to TT has been implicated ...Testicular torsion （TT） is a serious urologic emergency that is observed in adolescent males and that can lead to infertility if left untreated. The ischemia-reperfusion （I/R） injury due to TT has been implicated in the pathogenesis of testicular damage. We investigated the effects of melatonin on oxidative damage in the ipsUateral and contralateral testes of rats induced by unilateral TT. A total of 21 prepubertal male Wistar albino rats were divided into three groups, each consisting of seven rats, In Group 1 （SHAM group）： a sham operation to the left testis and bilateral orchiectomy were performed. In Group 2 （I/R group）： I/R injury was created by rotating the left testis 720° in a clockwise direction for 2 h and detorsing the testis after 2 h. Group 3 （I/R ＋ MEL group）： rats were subjected to I/R injury and one-shot melatonin injection （50mgkg-1, intraperitoneal （i.p.））. The testes of the rats were excised bilaterally in all groups. The testicular tissue activities of antioxidant catalase （CAT）, superoxide dismutase （SOD） and glutathione peroxidase enzymes （GSH-Px）, and the tissue levels of malondialdehyde （MDA）, protein carbonyl （PC） and nitric oxide （NO） were determined. Administration of melatonin caused a significant decrease in lipid peroxidation and enzyme activities in the ipsilateral testis when compared with the control group （P 〈 0.05）. All of the changes in the enzyme activities of the contralateral testis were insignificant （P 〉 0.05）. MDA levels were significantly altered in the contralateral testis （P = 0.009）, Melatonin administration decreased the deleterious effects of I/R injury in the ipsilateral torted testes of the rats. The contralateral testes were slightly affected by unilateral TT.展开更多
Here we summarize and discuss the body of information concerning mechanisms and regulation of local short-duration preconditioning that may accompany experimental radiation therapy. Based on the results of our previou...Here we summarize and discuss the body of information concerning mechanisms and regulation of local short-duration preconditioning that may accompany experimental radiation therapy. Based on the results of our previous studies in vivo we investigated possible impact of local temporary ischemia on the effectiveness of ionizing radiation-based anti-cancer therapy. We used total body-irradiated or abdomen only-irradiated healthy rats. Chosen blood parameters, changes in bone marrow cytological picture as well as histological picture of the small intestine were used as toxicity markers. We found a significant transient modification in lipid peroxides, triglycerides, uric acid concentration, SOD isoenzymes activity in the rat serum, increased numbers of small intestine crypts and suppression of bone marrow polychromatic erythrocytes and polychromatic erythrocytes with micronuclei. No significant differences were observed in MnSOD isoenzyme activity in serum and in small intestine homogenates after local temporary ischemia, nor after irradiation, nor combined treatment. Some differences were observed in intestinal tissue CuZnSOD activities. Nevertheless, great variations in response to ischemia, radiation or combined treatment was noted concerning this parameter. Histological picture of the small intestine from ionizing radiation-treated rats has indicated a marked protection of crypt survival by local temporary ischemic preconditioning. Some of the ionizing radiation-caused toxic effects were reduced in animals treated with local ischemic preconditioning. Together, these results provide a new insight into development of a more effective anticancer therapy combining short-duration ischemia and ionizing radiation modality.展开更多
Objective ：To study the effects of Ginkgo biloba extract （GBE） on lipid peroxidation and apoptosis after spinal cord ischemia/reperfusion （I/R） in rabbits. Methods： Spinal cord I/R injury model was established ...Objective ：To study the effects of Ginkgo biloba extract （GBE） on lipid peroxidation and apoptosis after spinal cord ischemia/reperfusion （I/R） in rabbits. Methods： Spinal cord I/R injury model was established according to the description of Erten et al. A total of 27 New Zealand white rabbits were divided into three groups randomly： a sham group （9 rabbits treated with sham operation but without aortic occlusion）, a model group （9 rabbits treated with aortic occlusion and volumematched saline）, and a GBE group （9 rabbits treated with aortic occlusion and Ginaton （100 mg/ kg ） injected 30 minutes before aortic clamping and at the onset of reperfusion）. The neurological outcomes were evaluated at 24 and 48 hours after reperfusion, respectively. The spinal cord malondialdehyde （MDA） level, superoxide dismutase （SOD） were then detected. Neural cell apoptosis was determined by terminal deoxynucleotidyl trausferase （TdT）-mediated dUTP-fluorescence nick end labeling （TUNEL） method and the expression of bcl-2 and bax were examined histologically in the spinal cord with immunohistochemistry. Results： I/R produced a significant decrease in neurological scoring. The motor scores of the GBE group were significantly higher than those of the model group at 24 and 48 hours after reperfusion （ P 〈 0.05 ）. Compared with the model group, GBE ameliorated the down. regulation of SOD and produced a significant reduction of the MDA level （ P 〈 0.01 ）. The positive cells for TUNEL in the model group were much more than those of the GBE group （P〈0.01）. The bcl-2 was up-regulated after I/R, especially in the GBE group （ P 〈 0. 01 ）. The up-regulation of bax was greatly diminished by GBE （ P 〈 0.01 ）. Conclusions： GBE has protective effects against spinal cord I/R injury, and the mechanism may be that it can scavenge oxygen free radicals and inhibit the apoptosis of neural cells.展开更多
基金the Ministry of Science and Technology of China(2018YFC1312300)National Natural Science Foundation of China(81722016,81801182)+1 种基金Sichuan Science and Technology Program(2018JPT0037,2018SZ0190)China Postdoctoral Science Foundation(2017M623041)。
文摘Ischemia/reperfusion(I/R) is a pathological process that occurs in numerous organs throughout the human body, and it is frequently associated with severe cellular damage and death. Recently it has emerged that ferroptosis, a new form of regulated cell death that is caused by iron-dependent lipid peroxidation, plays a significantly detrimental role in many I/R models. In this review, we aim to revise the pathological process of I/R and then explore the molecular pathogenesis of ferroptosis. Furthermore,we aim to evaluate the role that ferroptosis plays in I/R, providing evidence to support the targeting of ferroptosis in the I/R pathway may present as a therapeutic intervention to alleviate ischemia/reperfusion injury(IRI) associated cell damage and death.
基金supported by the National Natural Science Foundation of China,No.31770385(to SQJ)
文摘Orientin is a flavonoid monomer.In recent years,its importance as a source of pharmacological active substance is growing rapidly due to its properties such as anti-myocardial ischemia,anti-apoptosis,anti-radiation,anti-tumor,and anti-aging.However,the neuroprotective effects of Orientin on stroke injury have not been comprehensively evaluated.The aim of the present study was thus to investigate the neuroprotective capacity and the potential mechanisms of Cyperus esculentus L.orientin(CLO)from Cyperus esculentus L.leaves against ischemia/reperfusion(I/R)injury using standard orientin as control.For in vitro studies,we treated HT22 cells with CoCl2 as an in vitro ischemic injury model.HT22 cells in the control group were treated with CoCl2.For in vivo studies,we used rat models of middle cerebral artery occlusion,and animals that received sham surgery were used as controls.We found that CLO protected CoCl2-induced HT22 cells against ischemia/reperfusion injury by lowering lipid peroxidation and reactive oxygen species formation as well as decreasing protein oxidation.However,CLO did not reduce the release of lactate dehydrogenase nor increase the activity of superoxide dismutase.Results showed that CLO could decrease neurological deficit score,attenuate brain water content,and reduce cerebral infarct volume,leading to neuroprotection during cerebral ischemia-reperfusion injury.Our studies indicate that CLO flavonoids can be taken as a natural antioxidant and bacteriostastic substance in food and pharmaceutical industry.The molecular mechanisms of CLO could be at least partially attributed to the antioxidant properties and subsequently inhibiting activation of casepase-3.All experimental procedures and protocols were approved on May 16,2016 by the Experimental Animal Ethics Committee of Xinjiang Medical University of China(approval No.IACUC20160516-57).
文摘AIM: To investigate the protective effect of lansoprazoleon ischemia and reperfusion (I/R)-induced rat intestinalmucosal injury in vivo.METHODS: Intestinal damage was induced by clampingboth the superior mesenteric artery and the celiac trunkfor 30 rain followed by reperfusion in male Sprague-Dawleyrats. lansoprazole was given to rats intraperitoneally 1 hbefore vascular clamping.RESULTS: Both the intraluminal hemoglobin and proteinlevels, as indices of mucosal damage, significantlyincreased in I/R-groups comparion with those of sham-operation groups. These increases in intraluminal hemoglobinand protein levels were significantly inhibited by the treatmentwith lansoprazole at a dose of 1 mg/kg. Small intestineexposed to I/R resulted in mucosal inflammation that wascharacterized by significant increases in thiobarbituric acid-reactive substances (TBARS), tissue-associatedmyeloperoxidase activity (MPO), and mucosal content of ratcytokine-induced neutrophil chemoattractant-1 (CINC-1).These increases in TBARS, MPO activities and CINC-1 contentin the intestinal mucosa after I/R were all inhibited bypretreatment with lansoprazole at a dose of 1 mg/kg.Furthermore, the CINC-1 mRNA expression was increasedduring intestinal I/R, and this increase in mRNA expressionwas inhibited by treatment with lansoprazole.CONCLUSION: Lansoprazole inhibits lipid peroxidation andreduces development of intestinal mucosal inflammationinduced by I/R in rats, suggesting that lansoprazole mayhave a therapeutic potential for I/R injury.
文摘AIM： To compare different preconditioning strategies to protect the liver from ischemia/reperfusion injury focusing on the expression of pro- and anti-apoptotic proteins. Interventions comprised different modes of ischemic preconditioning （IP） as well as pharmacologic pretreatment by α-lipoic acid （LA）. METHODS： Several groups of rats were compared： sham operated animals, non-pretreated animals （nt）, animals receiving IP （10 rain of ischemia by clamping of the portal triad and 10 min of reperfusion） prior to sustained ischemia, animals receiving selective ischemic preconditioning （IPsel, 10 min of ischemia by selective clamping of the ischemic lobe and 10 rain of reperfusion） prior to sustained ichemia, and animals receiving 500 1μmol α-LA injected i.v. 15 min prior to the induction of 90 min of selective ischemia. RESULTS： Cellular damage was decreased only in the LA group. TUNEL-positive hepatocytes as well as necrotic hepatocyte injury were also decreased only by LA（19 ± 2 vs 10 ± 1, P〈 0.05 and 29 ± 5 vs 12 ± 1, P 〈 0.05）. Whereas caspase 3- activities in liver tissue were unchanged, caspase 9- activity in liver tissue was decreased only by LA pretreatment （3.1 ± 0.3 vs 1.8 ± 0.2, P 〈 0.05）. Survival rate as the endpoint of liver function was increased after IP and LA pretreatment but not after IPsel. Levels of lipid peroxidation （LPO） in liver tissue were decreased in the IP as well as in the LA group compared to the nt group. Determination of pro- and anti-apoptotic proteins showed a shift towards anti-apoptotic proteins by LA. In contrast, both our IP strategies failed to influence apototic cell death. CONCLUSION： IP, consisting of 10 min of ischemia and 10 min of reperfusion, ischemia/reperfusion injury protects only partly against of the liver prior to 90 min of selective ischemia. IPsel did not influence ischemic tolerance of the liver. LA improved tolerance to ischemia, possibly by downregulation of pro-apoptotic Bax.
文摘Objective To investigate the possible protection provided by oral quercetin pretreatment against hepatic ischemia-reperfusion injury in rats. Methods The quercetin （0.13 mmol/kg） was orally administrated in 50 min prior to hepatic ischemia-reperfusion injury. Ascorbic acid was also similarly administered. The hepatic content of quercetin was assayed by high performance liquid chromatography （HPLC）. Plasma glutamic pyruvic transaminase （GPT）, glutamic oxaloacetic transaminase （GOT） activities and malondialdehyde （MDA） concentration were measured as markers of hepatic ischemia-reperfusion injury. Meanwhile, hepatic content of glutathione （GSH）, activities of superoxide dismutase （SOD）, glutathione peroxidase （GSH-Px） and xanthine oxidase （XO）, total antioxidant capacity （TAOC）, contents of reactive oxygen species （ROS） and MDA, DNA fragmentation were also determined. Results Hepatic content of quercetin after intragastric administration of quercetin was increased significantly. The increases in plasma GPT
文摘Testicular torsion （TT） is a serious urologic emergency that is observed in adolescent males and that can lead to infertility if left untreated. The ischemia-reperfusion （I/R） injury due to TT has been implicated in the pathogenesis of testicular damage. We investigated the effects of melatonin on oxidative damage in the ipsUateral and contralateral testes of rats induced by unilateral TT. A total of 21 prepubertal male Wistar albino rats were divided into three groups, each consisting of seven rats, In Group 1 （SHAM group）： a sham operation to the left testis and bilateral orchiectomy were performed. In Group 2 （I/R group）： I/R injury was created by rotating the left testis 720° in a clockwise direction for 2 h and detorsing the testis after 2 h. Group 3 （I/R ＋ MEL group）： rats were subjected to I/R injury and one-shot melatonin injection （50mgkg-1, intraperitoneal （i.p.））. The testes of the rats were excised bilaterally in all groups. The testicular tissue activities of antioxidant catalase （CAT）, superoxide dismutase （SOD） and glutathione peroxidase enzymes （GSH-Px）, and the tissue levels of malondialdehyde （MDA）, protein carbonyl （PC） and nitric oxide （NO） were determined. Administration of melatonin caused a significant decrease in lipid peroxidation and enzyme activities in the ipsilateral testis when compared with the control group （P 〈 0.05）. All of the changes in the enzyme activities of the contralateral testis were insignificant （P 〉 0.05）. MDA levels were significantly altered in the contralateral testis （P = 0.009）, Melatonin administration decreased the deleterious effects of I/R injury in the ipsilateral torted testes of the rats. The contralateral testes were slightly affected by unilateral TT.
文摘Here we summarize and discuss the body of information concerning mechanisms and regulation of local short-duration preconditioning that may accompany experimental radiation therapy. Based on the results of our previous studies in vivo we investigated possible impact of local temporary ischemia on the effectiveness of ionizing radiation-based anti-cancer therapy. We used total body-irradiated or abdomen only-irradiated healthy rats. Chosen blood parameters, changes in bone marrow cytological picture as well as histological picture of the small intestine were used as toxicity markers. We found a significant transient modification in lipid peroxides, triglycerides, uric acid concentration, SOD isoenzymes activity in the rat serum, increased numbers of small intestine crypts and suppression of bone marrow polychromatic erythrocytes and polychromatic erythrocytes with micronuclei. No significant differences were observed in MnSOD isoenzyme activity in serum and in small intestine homogenates after local temporary ischemia, nor after irradiation, nor combined treatment. Some differences were observed in intestinal tissue CuZnSOD activities. Nevertheless, great variations in response to ischemia, radiation or combined treatment was noted concerning this parameter. Histological picture of the small intestine from ionizing radiation-treated rats has indicated a marked protection of crypt survival by local temporary ischemic preconditioning. Some of the ionizing radiation-caused toxic effects were reduced in animals treated with local ischemic preconditioning. Together, these results provide a new insight into development of a more effective anticancer therapy combining short-duration ischemia and ionizing radiation modality.
文摘Objective ：To study the effects of Ginkgo biloba extract （GBE） on lipid peroxidation and apoptosis after spinal cord ischemia/reperfusion （I/R） in rabbits. Methods： Spinal cord I/R injury model was established according to the description of Erten et al. A total of 27 New Zealand white rabbits were divided into three groups randomly： a sham group （9 rabbits treated with sham operation but without aortic occlusion）, a model group （9 rabbits treated with aortic occlusion and volumematched saline）, and a GBE group （9 rabbits treated with aortic occlusion and Ginaton （100 mg/ kg ） injected 30 minutes before aortic clamping and at the onset of reperfusion）. The neurological outcomes were evaluated at 24 and 48 hours after reperfusion, respectively. The spinal cord malondialdehyde （MDA） level, superoxide dismutase （SOD） were then detected. Neural cell apoptosis was determined by terminal deoxynucleotidyl trausferase （TdT）-mediated dUTP-fluorescence nick end labeling （TUNEL） method and the expression of bcl-2 and bax were examined histologically in the spinal cord with immunohistochemistry. Results： I/R produced a significant decrease in neurological scoring. The motor scores of the GBE group were significantly higher than those of the model group at 24 and 48 hours after reperfusion （ P 〈 0.05 ）. Compared with the model group, GBE ameliorated the down. regulation of SOD and produced a significant reduction of the MDA level （ P 〈 0.01 ）. The positive cells for TUNEL in the model group were much more than those of the GBE group （P〈0.01）. The bcl-2 was up-regulated after I/R, especially in the GBE group （ P 〈 0. 01 ）. The up-regulation of bax was greatly diminished by GBE （ P 〈 0.01 ）. Conclusions： GBE has protective effects against spinal cord I/R injury, and the mechanism may be that it can scavenge oxygen free radicals and inhibit the apoptosis of neural cells.
