Etomidate affects the anti-oxidant pathway to protect retinal ganglion cells after optic nerve transection
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摘要
Our previous studies revealed that etomidate, a non-barbiturate intravenous anesthetic agent, has protective effects on retinal ganglion cells within 7 days after optic nerve transection. Whether this process is related to anti-oxidative stress is not clear. To reveal its mechanism, we established the optic nerve transection injury model by transecting 1 mm behind the left eyeball of adult male Sprague-Dawley rats. The rats received an intraperitoneal injection of etomidate(4 mg/kg) once per day for 7 days. The results showed that etomidate significantly enhanced the number of retinal ganglion cells retrogradely labeled with Fluorogold at 7 days after optic nerve transection. Etomidate also significantly reduced the levels of nitric oxide and malonaldehyde in the retina and increased the level of glutathione at 12 hours after optic nerve transection. Thus, etomidate can protect retinal ganglion cells after optic nerve transection in adult rats by activating an anti-oxidative stress response. The study was approved by the Animal Ethics Committee at Air Force Medical University, China(approval No. 20180305) on March 5, 2018.
Our previous studies revealed that etomidate, a non-barbiturate intravenous anesthetic agent, has protective effects on retinal ganglion cells within 7 days after optic nerve transection. Whether this process is related to anti-oxidative stress is not clear. To reveal its mechanism, we established the optic nerve transection injury model by transecting 1 mm behind the left eyeball of adult male Sprague-Dawley rats. The rats received an intraperitoneal injection of etomidate(4 mg/kg) once per day for 7 days. The results showed that etomidate significantly enhanced the number of retinal ganglion cells retrogradely labeled with Fluorogold at 7 days after optic nerve transection. Etomidate also significantly reduced the levels of nitric oxide and malonaldehyde in the retina and increased the level of glutathione at 12 hours after optic nerve transection. Thus, etomidate can protect retinal ganglion cells after optic nerve transection in adult rats by activating an anti-oxidative stress response. The study was approved by the Animal Ethics Committee at Air Force Medical University, China(approval No. 20180305) on March 5, 2018.
Our previous studies revealed that etomidate, a non-barbiturate intravenous anesthetic agent, has protective effects on retinal ganglion cells within 7 days after optic nerve transection. Whether this process is related to anti-oxidative stress is not clear. To reveal its mechanism, we established the optic nerve transection injury model by transecting 1 mm behind the left eyeball of adult male Sprague-Dawley rats. The rats received an intraperitoneal injection of etomidate(4 mg/kg) once per day for 7 days. The results showed that etomidate significantly enhanced the number of retinal ganglion cells retrogradely labeled with Fluorogold at 7 days after optic nerve transection. Etomidate also significantly reduced the levels of nitric oxide and malonaldehyde in the retina and increased the level of glutathione at 12 hours after optic nerve transection. Thus, etomidate can protect retinal ganglion cells after optic nerve transection in adult rats by activating an anti-oxidative stress response. The study was approved by the Animal Ethics Committee at Air Force Medical University, China(approval No. 20180305) on March 5, 2018.
引文
Ates O,Yucel N,Cayli SR,Altinoz E,Yologlu S,Kocak A,Cakir CO,Turkoz Y(2006)Neuroprotective effect of etomidate in the central nervous system of streptozotocin-induced diabetic rats.Neurochem Res 31:777-783.
Cayli SR,Ates O,Karadag N,Altinoz E,Yucel N,Yologlu S,Kocak A,Cakir CO(2006)Neuroprotective effect of etomidate on functional recovery in experimental spinal cord injury.Int J Dev Neurosci24:233-239.
Cheng HH,Ye H,Peng RP,Deng J,Ding Y(2018)Inhibition of retinal ganglion cell apoptosis:regulation of mitochondrial function by PA-CAP.Neural Regen Res 13:923-929.
Cheung ZH,Chan YM,Siu FK,Yip HK,Wu W,Leung MC,So KF(2004)Regulation of caspase activation in axotomized retinal ganglion cells.Mol Cell Neurosci 25:383-393.
Geiger LK,Kortuem KR,Alexejun C,Levin LA(2002)Reduced redox state allows prolonged survival of axotomized neonatal retinal ganglion cells.Neuroscience 109:635-642.
He L,He T,Farrar S,Ji L,Liu T,Ma X(2017)Antioxidants maintain cellular redox homeostasis by elimination of reactive oxygen species.Cell Physiol Biochem 44:532-553.
Kanamori A,Catrinescu MM,Kanamori N,Mears KA,Beaubien R,Levin LA(2010)Superoxide is an associated signal for apoptosis in axonal injury.Brain 133:2612-2625.
Lee J,Kim D,Hong H,Han S,Kim J(2000)Protective effect of etomidate on kainic acid-induced neurotoxicity in rat hippocampus.Neurosci Lett 286:179-182.
Rovere G,Nadal-Nicolás FM,Sobrado-Calvo P,Villegas-Pérez MP,Vidal-Sanz M,Agudo-Barriuso M(2019)Topical bromfenac transiently delays axotomy-induced retinal ganglion cell loss.Exp Eye Res 182:156-159.
Sato T,Oku H,Tsuruma K,Katsumura K,Shimazawa M,Hara H,Sugiyama T,Ikeda T(2010)Effect of hypoxia on susceptibility of RGC-5cells to nitric oxide.Invest Ophthalmol Vis Sci 51:2575-2586.
Tezel G(2006)Oxidative stress in glaucomatous neurodegeneration:mechanisms and consequences.Prog Retin Eye Res 25:490-513.
Tezel G,Yang X(2004)Caspase-independent component of retinal ganglion cell death,in vitro.Invest Ophthalmol Vis Sci 45:4049-4059.
Tezel G,Wax MB(2004)The immune system and glaucoma.Curr Opin Ophthalmol 15:80-84.
Tezel G,Luo C,Yang X(2007)Accelerated aging in glaucoma:immunohistochemical assessment of advanced glycation end products in the human retina and optic nerve head.Invest Ophthalmol Vis Sci48:1201-1211.
Tsikas D(2017)Assessment of lipid peroxidation by measuring malondialdehyde(MDA)and relatives in biological samples:Analytical and biological challenges.Anal Biochem 524:13-30.
Vigneswara V,Ahmed Z(2019)Pigment epithelium-derived factor mediates retinal ganglion cell neuroprotection by suppression of caspase-2.Cell Death Dis 10:102.
Watson JC,Drummond JC,Patel PM,Sano T,Akrawi W,U HS(1992)An assessment of the cerebral protective effects of etomidate in a model of incomplete forebrain ischemia in the rat.Neurosurgery30:540-544.
Weishaupt JH,Diem R,Kermer P,Krajewski S,Reed JC,B?hr M(2003)Contribution of caspase-8 to apoptosis of axotomized rat retinal ganglion cells in vivo.Neurobiol Dis 13:124-135.
Xu ZX,Hu JM,Xu GZ,Ma LT(2015)Etomidate promoting retinal ganglion cells survival after optic nerve transaction in adult rats via inhibition of PKC/NF-κB signaling.Yanke Xin Jinzhan 35:1121-1125.
Yamamoto K,Maruyama K,Himori N,Omodaka K,Yokoyama Y,Shiga Y,Morin R,Nakazawa T(2014)The novel Rho kinase(ROCK)inhibitor K-115:a new candidate drug for neuroprotective treatment in glaucoma.Invest Ophthalmol Vis Sci 55:7126-7136.
Cayli SR,Ates O,Karadag N,Altinoz E,Yucel N,Yologlu S,Kocak A,Cakir CO(2006)Neuroprotective effect of etomidate on functional recovery in experimental spinal cord injury.Int J Dev Neurosci24:233-239.
Cheng HH,Ye H,Peng RP,Deng J,Ding Y(2018)Inhibition of retinal ganglion cell apoptosis:regulation of mitochondrial function by PA-CAP.Neural Regen Res 13:923-929.
Cheung ZH,Chan YM,Siu FK,Yip HK,Wu W,Leung MC,So KF(2004)Regulation of caspase activation in axotomized retinal ganglion cells.Mol Cell Neurosci 25:383-393.
Geiger LK,Kortuem KR,Alexejun C,Levin LA(2002)Reduced redox state allows prolonged survival of axotomized neonatal retinal ganglion cells.Neuroscience 109:635-642.
He L,He T,Farrar S,Ji L,Liu T,Ma X(2017)Antioxidants maintain cellular redox homeostasis by elimination of reactive oxygen species.Cell Physiol Biochem 44:532-553.
Kanamori A,Catrinescu MM,Kanamori N,Mears KA,Beaubien R,Levin LA(2010)Superoxide is an associated signal for apoptosis in axonal injury.Brain 133:2612-2625.
Lee J,Kim D,Hong H,Han S,Kim J(2000)Protective effect of etomidate on kainic acid-induced neurotoxicity in rat hippocampus.Neurosci Lett 286:179-182.
Rovere G,Nadal-Nicolás FM,Sobrado-Calvo P,Villegas-Pérez MP,Vidal-Sanz M,Agudo-Barriuso M(2019)Topical bromfenac transiently delays axotomy-induced retinal ganglion cell loss.Exp Eye Res 182:156-159.
Sato T,Oku H,Tsuruma K,Katsumura K,Shimazawa M,Hara H,Sugiyama T,Ikeda T(2010)Effect of hypoxia on susceptibility of RGC-5cells to nitric oxide.Invest Ophthalmol Vis Sci 51:2575-2586.
Tezel G(2006)Oxidative stress in glaucomatous neurodegeneration:mechanisms and consequences.Prog Retin Eye Res 25:490-513.
Tezel G,Yang X(2004)Caspase-independent component of retinal ganglion cell death,in vitro.Invest Ophthalmol Vis Sci 45:4049-4059.
Tezel G,Wax MB(2004)The immune system and glaucoma.Curr Opin Ophthalmol 15:80-84.
Tezel G,Luo C,Yang X(2007)Accelerated aging in glaucoma:immunohistochemical assessment of advanced glycation end products in the human retina and optic nerve head.Invest Ophthalmol Vis Sci48:1201-1211.
Tsikas D(2017)Assessment of lipid peroxidation by measuring malondialdehyde(MDA)and relatives in biological samples:Analytical and biological challenges.Anal Biochem 524:13-30.
Vigneswara V,Ahmed Z(2019)Pigment epithelium-derived factor mediates retinal ganglion cell neuroprotection by suppression of caspase-2.Cell Death Dis 10:102.
Watson JC,Drummond JC,Patel PM,Sano T,Akrawi W,U HS(1992)An assessment of the cerebral protective effects of etomidate in a model of incomplete forebrain ischemia in the rat.Neurosurgery30:540-544.
Weishaupt JH,Diem R,Kermer P,Krajewski S,Reed JC,B?hr M(2003)Contribution of caspase-8 to apoptosis of axotomized rat retinal ganglion cells in vivo.Neurobiol Dis 13:124-135.
Xu ZX,Hu JM,Xu GZ,Ma LT(2015)Etomidate promoting retinal ganglion cells survival after optic nerve transaction in adult rats via inhibition of PKC/NF-κB signaling.Yanke Xin Jinzhan 35:1121-1125.
Yamamoto K,Maruyama K,Himori N,Omodaka K,Yokoyama Y,Shiga Y,Morin R,Nakazawa T(2014)The novel Rho kinase(ROCK)inhibitor K-115:a new candidate drug for neuroprotective treatment in glaucoma.Invest Ophthalmol Vis Sci 55:7126-7136.