Neuroprotective effects of sea buckthorn leaf extract against hypobaric hypoxia and post-hypoxic reoxygenation induced hippocampal damage in rats.
Keywords:Hypobaric hypoxia, Hippocampus, Hippophae rhamnoides L, Glutathione, oxidative stress, Reoxygenation
Exposure to hypobaric hypoxia (HBH) and reoxygenation (H/R) causes hippocampal neuronal damage leading to memory dysfunction and mood state alteration. The present study aimed at investigating the potential neuroprotective effect of seabuckthorn leaf extract ((SBTLE)) against HBH and reoxygenation induced neuronal injury in brain. Six groups of male sprague dawley rats were taken and exposed to simulated HBH equivalent at an altitude of 7600m in an animal decompression chamber for 7 days followed by reoxygenation. Rats were supplemented with SBTLE (100mg/kgBW) 20 days prior and during hypoxic exposure. Recovery from injuries following HBH exposure and subsequent reoxygenation was carried out in separate group of animals. Our study revealed that exposure to reoxygenation stress following hypoxia enhanced hypoxia induced oxidative stress in hippocampal neurons which was reversed with SBTLE supplementation. SBTLE restored Hypoxia/Reoxygenation(H/R) induced downregulation of γ-glutamylcysteine synthetase (GCLC) enzymes responsible for glutathione biosynthesis. Post hypoxic supplementation of SBTLE decreased the reoxygenation induced enhanced oxidative markers, however, administration of SBTLE in conjunction with the inhibitor of GCLC resulted in slow recovery from H/R injuries. These results provide the first evidence of SBTLE induced increase in glutathione biosynthesis by upregulating GCLC enzyme expression and hence can be used as a promising drug to cure H/R induced neuronal damages.
. Shukitt-Hale B, Banderet LF, Lieberman HR. Elevation-dependent symptom, mood and performance changes produced by exposure to hypobaric hypoxia. Int J Acta Psychol. 1998; 8 (4): 319-34.
. Baumgartner RW, Eivhenberger V, Bartsch P. Postural ataxia at high altitude is not related to mild to moderate acute mountain sickness. Eur J Appl Physiol. 2002; 86: 322–26.
. Hota SK, Barhwal K, Ray K, Singh SB, Ilavazhagan G. Ceftriaxone rescues hippocampal neurons from excitotoxicity and enhances memory retrieval in chronic hypobaric hypoxia. Neurobiol Learn Mem. 2008; 89: 522–32.
. Maiti P, Singh SB, Sharma AK, Muthuraju S, Banerjee PK, Ilavazhagan G. Hypobaric hypoxia induces oxidative stress in rat brain. Neurochem Int. 2006; 49(8): 709-16.
. Baitharu I, Deep SN, Jain V, Barhwal K, Malhotra AS, Hota SK, Prasad D, Ilavazhagan G. Corticosterone synthesis inhibitor metyrapone ameliorates chronic hypobaric hypoxia induced memory impairment in rat. Behav Brain Res. 2012; 228(1):53-65.
. Soane L, Li Dai W, Fiskum G, Bambrick LL. Sulforaphane protects immature hippocampal neurons against death caused by exposure to hemin or to oxygen and glucose deprivation. J Neurosci Res. 2010; 88(6): 1355-63.
. González-Correa JA, Arrebola MM, Cansino AL, Muñoz-Marín J, Ruiz Villafranca D, Guerrero A, de la Cuesta FS, De La Cruz JP. Effects of hypoxia reoxygenation in brain slices from rats with type 1-like diabetes mellitus. Diabetes Metab Res Rev. 2006; 22 (5): 390-400.
. Graulich J, Hoffmann U, Maier RF, Ruscher K, Pomper JK, Ko HK, Gabriel S, Heinemann U. Acute neuronal injury after hypoxia is influenced by the reoxygenation mode in juvenile hippocampal slice cultures. Developmental Brain Res. 2002; 137 (1): 35-42.
. Chan PH. Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab. 2001; 21: 2-14.
. Hota SK, Barhwal K, Ray K, Singh SB, Ilavazhagan G. Ceftriaxone rescues hippocampal neurons from excitotoxicity and enhances memory retrieval in chronic hypobaric hypoxia. Neurobiol Learn Mem. 2008;89(4):522-32.
. Barhwal K, Hota SK, Baitharu I, Prasad D, Singh SB, Ilavazhagan G. Isradipine antagonizes hypobaric hypoxia induced CA1 damage and memory impairment: Complementary roles of L- type calcium channel and NMDA receptors. Neurobiol Dis. 2009; 34: 230–44.
. Muthuraju S, Maiti P, Solanki P, Sharma AK, Singh SB, Prasad D, Ilavazhagan G. Cholinesterase inhibitors ameliorate spatial learning deficits in rats following hypobaric hypoxia. Exp Brain Res. 2010; 203(3): 583-92.
. Lu R. Seabuckthorn: A Multipurpose Plant Species for Fragile Mountains. ICIMOD Publication Unit, Katmandu, Nepal,1992.
. Geetha S, Sai Ram M, Singh V, Ilavazhagan G, Sawhney RC. Anti-oxidant and immunomodulatory properties of seabuckthorn (Hippophae rhamnoides)--an in vitro study. J Ethnopharmacol. 2002; 79: 373-8.
. Yogendra Kumar MS, Dutta R, Prasad D, Misra K. Subcritical water extraction of antioxidant compounds from Seabuckthorn (Hippophae rhamnoides) leaves for the comparative evaluation of antioxidant activity. Food Chem. 2011; 127: 1309–16.
. LeBel CP, Ali SF, McKee M, Bondy SC.Organometal-induced increases in oxygen reactive species:the potential of 2’,7’-dichlorofluorescin diacetate as an index of neurotoxic damage. Toxicol Appl Pharmacol. 1990; 104(1): 17-24.
. Utley HG, Bergheim F, Hochstein P. Effect of sulfydryl reagents on peroxidation of microsomes. Arch Biochem Biophys. 1967; 118:29-32.
. Hissin PJ, Hilf R. A fluorimetric method for determination of oxidized and reduced glutathione in tissues. Ann Biochem. 1976; 76: 214-26.
. Pinto RE, Bartley W. The effect of age and sex on gluthatione reductase and gluthathione peroxidase activities and on aerobic gluthatione oxidation in rat liver homogenates. Biochem.J. 1969; 112(1): 109-15.
. Hota SK, Barhwal K, Singh SB, Ilavazhagan G. Differential temporal response of hippocampus, cortex and cerebellum to hypobaric hypoxia: a biochemical approach. Neurochem Int. 2007; 51(6-7):384-90.
. Baitharu I, Jain V, Deep SN, Hota KB, Hota SK, Prasad D, Ilavazhagan G. Withania somnifera root extract ameliorates hypobaric hypoxia induced memory impairment in rats. J Ethnopharmacol. 2013; 145(2):431-41.
. McCord JM. Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med.1985; 312: 159–63.
. Nakanishi K, Tajima F, Nakamura A, Yagura S, Ookawara T, Yamashita H, Suzuki K, Taniguchi N, Ohno H. Effects of hypobaric hypoxia on antioxidant enzymes in rats. J Physiol. 1995; 489 (3): 869-76.
. Gao ZI, Gu XH, Cheng FT, Jiang FH. Effects of Seabuckthorn on liver fibrosis: a clinical study. World J Gastroenterol. 2003; 19(7): 1615-17.
. Narayanan S, Ruma D, Gitika B, Sharma SK, Pauline T, Sairam M, Ilavazhagan, G, Sawhney RC, Kumar D, Banerjee PK. Antioxidant activities of seabuckthorn (Hippophae rhamnoides) during hypoxia induced oxidative stress in glial cells. Mol Cell Biochem. 2005; 278: 9-14.
. Geetha S, Sairam M, Mongia SS, Singh V, Ilavazhagan G, Sawhney RC. Evaluation of antioxidant activity of leaf extracts of Sea buckthorn (Hippophae rhamnoides) on chromium (VI). J Ethnopharmacol. 2003; 87: 247-51.
. Schild L, Reiser G. Oxidative stress is involved in the permeabilization of the inner membrane of brain mitochondria exposed to hypoxia/reoxygenation and low micromolar Ca. FEBS J. 2005; 272: 3569–601.
. Oliver CN, Starke-Reed PE, Stadtman ER. Oxidative damage to brain proteins, loss of glutamine synthetase activity, and production of free radicals during ischemia/reperfusion- induced injury in gerbil brain. Proc Natl Acad Sci USA. 1990; 87: 5144–5147.
. Zuo L, Clanton TL. Reactive oxygen species formation in the transition to hypoxia in skeletal muscle. Am J Physiol Cell Physiol. 2005; 289: C207–16.
. Baitharu I, Deep SN, Jain V, Prasad D, Ilavazhagan G. Inhibition of glucocorticoid receptors ameliorates hypobaric hypoxia induced memory impairment in rat. Behav Brain Res. 2013; 240:76-86.
. Chuanyu L and Robert MJ. Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am J Physiol Cell Physiol. 2002; 282: C227–C241.
. Barker JE, Heales SJR, Cassidy A, Belanos JP, Land JM, Clark JB. Depletion of brain gluthatione results in a decrease in glutathione reductase activity: an enzyme susceptible to oxidative damage. Brain Res. 1996; 716: 118-22.
. Zhang Y, Marcillat O, Giulivi C, Ernster L, Davies KJ. The oxidative inactivation of mitochondrial electron transport chain components and ATPase. J Biol Chem. 1990; 265: 16330– 36.
. Ishige K, Schubert D, Sagara Y. Flavonoids protect neuronal cells from oxidative stress by three distinct mechanisms. Free Radical Biol Med. 2001; 30(4): 433- 46.
. Hota SK, Barhwal K, Baitharu I, Prasad D, Singh SB, Ilavazhagan G. Bacopa monniera leaf extract ameliorates hypobaric hypoxia induced spatial memory impairment. Neurobiol Dis. 2009; 34(1):23-39.
. Shivakumar BR, Kolluri SV, Ravindranath V. Glutathione and protein thiol homeostasis in brain during reperfusion after cerebral ischemia. J Pharmacol Exp Ther. 1995; 274(3): 1167-73.
. Chia AJ, Goldring CE, Kitteringham NR, Wong SQ, Morgan P, Park BK. Differential effect of covalent protein modification and glutathione depletion on the transcriptional response of Nrf2 and NF-kappaB. Biochem Pharmacol. 2010;80(3):410-21.
. Mizui T, Kinouchi H, Chan PH. Depletion of brain glutathione by buthionine sulfoximine enhances cerebral ischemic injury in rats. Am J Physiol. 1992; 262: H313-7.