Comparison of taurine, GABA, Glu, and Asp as scavengers of malondialdehyde in vitro and in vivo
- Yan Deng†1, 2Email author,
- Wei Wang†1,
- Pingfeng Yu3,
- Zhijiang Xi2,
- Lijian Xu1,
- Xiaolong Li1, 2 and
- Nongyue He1, 2Email author
© Deng et al.; licensee Springer. 2013
Received: 22 March 2013
Accepted: 5 April 2013
Published: 24 April 2013
The purpose of this study is to determine if amino acid neurotransmitters such as gamma-aminobutyric acid (GABA), taurine, glutamate (Glu), and aspartate (Asp) can scavenge activated carbonyl toxicants. In vitro, direct reaction between malondialdehyde (MDA) and amino acids was researched using different analytical methods. The results indicated that scavenging activated carbonyl function of taurine and GABA is very strong and that of Glu and Asp is very weak in pathophysiological situations. The results provided perspective into the reaction mechanism of taurine and GABA as targets of activated carbonyl such as MDA in protecting nerve terminals. In vivo, we studied the effect of taurine and GABA as antioxidants by detecting MDA concentration and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. It was shown that MDA concentration was decreased significantly, and the activities of SOD and GSH-Px were increased significantly in the cerebral cortex and hippocampus of acute epileptic state rats, after the administration of taurine and GABA. The results indicated that the peripherally administered taurine and GABA can scavenge free radicals and protect the tissue against activated carbonyl in vivo and in vitro.
There is a common character for all neurodegenerative diseases: all of which, such as Parkinson's disease (PD) and Alzheimer's disease (AD), are connected with neuronal apoptosis induced by oxidative stress and carbonyl stress [1, 2]. Oxidative injury plays a role in the initiation and progression of epilepsy . In pathophysiological situations of the brain, the high metabolic rate, low concentration of glutathione and antioxidant enzyme catalase, and high proportion of polyunsaturated fatty acids make the brain tissue and DNA particularly susceptible to oxidative and carbonyl damage causing neurodegenerative disorders [4–6]. The Maillard reaction and advanced lipid peroxidation reactions lead to the formation of advanced glycation end products (AGEs) and advanced lipoxidation end products (ALEs), whose processes have been widely documented to be responsible for the formation of various age pigment-like fluorophores and many chronic diseases, such as neuronal degenerative diseases, chronic fatigue syndrome, and physiological aging [7–11]. A variety of reactive carbonyl intermediates derived from Maillard and lipid peroxidation reactions acts as intermediates in the formation of AGEs and ALEs [12, 13]. These carbonyl compounds were found to react readily with an amino group of proteins with the formation of protein aggregates, resulting in protein structural and functional alterations .
Malondialdehyde (MDA) is the well-studied intermediate of oxidative stress . These reactive unsaturated carbonyls can target a variety of biological components, such as structural and functional proteins and nucleic acids [7, 16]. MDA causes tissue injury and the depression of energy metabolism, thus representing biochemical markers for disease progression and lipid peroxidation, such as Huntington's disease , familial amyotrophic lateral sclerosis (ALS) , AD, and vascular dementia [19, 20]. Recent research results suggest that schizophrenic patients exhibit increased MDA levels, which lead to neuronal damage . ALEs such as MDA have been implicated in the neuronal loss observed in a variety of neuropathological cases including AD, ALS, PD, and ischemia [2, 16, 22]. These findings further support a role of carbonyl injury in the pathogenesis and the potential benefits of antioxidant therapy .
Taurine (2-aminoethanesulfonic acid) and gamma-aminobutyric acid (GABA) are both natural amino acids with wide occurrence. In the context of the neural system, taurine and GABA are inhibitory amino acid neurotransmitters, and glutamate and aspartate are excitatory amino acids. Taurine was originally described to inhibit lipid peroxidation . At present, taurine has been demonstrated to protect the brain against lipid peroxidation and oxidative stress [25, 26]. It has also been shown that GABA exhibits anti-hypertensive effect, activates the blood flow, and increases the oxygen supply in the brain to enhance metabolic function of brain cells . Evidence suggests GABA-improved visual cortical function in senescent monkeys . Decreased proportion of GABA associated with age-related degradation of neuronal function and neuronal degenerative diseases . Recent study showed GABA-alleviated oxidative damage . Glutamate (Glu) and aspartate (Asp) are reported to prevent cardiac toxicity by alleviating oxidative stress . In this paper, it is hypothesized that several amino acids may inhibit the formation of ALEs and scavenge reactive carbonyl compounds such as MDA based on a potential carbonyl-amine reaction under physiological conditions, and its function is in vitro compared; also, the strong inhibition function of amino acids was investigated in vivo.
Materials and preparation
Taurine, GABA, Glu, and Asp were purchased from Sinopharm Chemical Reagent C., Ltd (Shanghai, China). 1,1,3,3-Tetramethoxypropane (TMP) and pentylenetetrazol (PTZ) were obtained from Fluka Chemie AG (Buchs, Switzerland). MDA detection kit, superoxide dismutase (SOD) detection kit, glutathione peroxidase (GSH-Px) detection kit, and total protein quantification kit (Coomassie Brilliant Blue) were purchased from Nanjing Jiancheng Bioengineering Institute (Nanjing, China). Other chemicals used were purchased from HuiHong Chemical Reagent C., Ltd. (Changsha, China).
MDA stock solution (40 mM) was prepared by hydrolyzing TMP according to a method described by Kikugawa and Beppu . Thus, 0.17 mL (1.0 mmol) of TMP was added in 4 mL of 1.0 M HCl and shaken at 40°C for about 2 min. After the TMP was fully hydrolyzed, the pH was adjusted to 7.4 with 6.0 M NaOH, and the stock solution was finally made up to 25 mL with 0.2 M PBS (pH 7.4). The stock solution was checked by measuring the absorbance at 266 nm using ϵ266 = 31,500 M−1 cm−1.
In vitro incubation experiments and HPLC, fluorescence, and LC/MS analysis of the incubation mixture
Several amino acids were incubated with MDA (5.0 mM) in 5 mL of 0.2 M PBS at 37°C (pH 7.4). Samples were analyzed by high-performance liquid chromatography (HPLC), fluorescence, or liquid chromatography/mass spectrometry (LC/MS) [26, 33].
Animals and drug treatment
Male or female Sprague–Dawley rats (180 to 230 g) were employed for the experiments (Shanghai Experimental Animal Center, Chinese Academy of Sciences). Five rats were kept in individual cages with water and food available ad libitum. The animal room was maintained at 21°C to 23°C, with a 12-h light–dark cycle. All experimental procedures were approved by the Committee of Laboratory Animals, Chinese Academy of Sciences.
Rats were intraperitoneally (i.p.) administered with 70-mg/kg dose of 1% PTZ (dissolved in saline) to induced auditory evoked potential (AEP). Control animals received the same amount of saline injections. The seizures were rated according to the following criteria [34, 35]: stage 0, no response; stage I, ear and facial twitching; stage II, myoclonic jerks without upright position; stage III, myoclonic jerks, upright position with bilateral forelimb clonus; stage IV, clonic-tonic seizure; and stage V, generalized clonic-tonic seizures, loss of postural control.
Experimental rats were divided into four groups as follows: group 1, rats were treated with saline; group 2, rats were i.p. injected with a dose of 70 mg/kg PTZ to induce the onset of seizures; group 3, rats were i.p. co-administered with a dose of 70 mg/kg PTZ since i.p. injected with a dose of 500 mg/kg taurine after 30 min; and group 4, rats were i.p. co-administered with a dose of 70 mg/kg PTZ since i.p. injected with a dose of 500 mg/kg GABA after 30 min. After 1 h, the animals were killed, the brains were dissected, the cerebral cortex and hippocampus tissues were removed, and blood was withdrawn. The brain tissue was rinsed in ice-cold normal saline, added to nine times ice-cold normal saline, homogenized, and centrifuged at 5,000×g for 15 min at 4°C. The blood was centrifuged at 3,000×g for 15 min. The supernatant and serum were obtained and stored in a −20°C refrigerator for MDA assays and antioxidant enzymes' (SOD, GSH-Px) activity assays. The protein concentration was determined by Coomassie Brilliant Blue method.
MDA assay and antioxidant enzyme activity measurement
The MDA and antioxidant enzymes' (SOD, GSH-Px) activity of the cerebral cortex and the hippocampus tissue and blood from PTZ-induced AEP were evaluated by MDA assay and antioxidant enzymes' (SOD, GSH-Px) kits according to the manufacturer's instructions.
Data were shown as mean ± S.E.M. Statistical evaluation was carried out by one-way analysis of variance (ANOVA) followed by Scheffe's multiple range tests. P < 0.05 was considered to be significant.
Incubation products assayed by HPLC and fluorescence
UV absorption maxima and fluorescence Ex/Em values
UV absorption maxima (nm)
Fluorescence Ex/Em (nm)
236, 263, 391
231, 262, 394
Identification of reaction products by LC/MS
Comparison of the formation of reaction products of taurine, GABA, Glu, or Asp with MDA
Content of MDA in PTZ-induced acute epileptic state rats
Test result of MDA content of the hippocampus, cerebral cortex, and serum of every group
Hippocampus (nmol/mg protein)
Cerebral cortex (nmol/mg protein)
Control + NS
14.20 ± 4.54*
14.87 ± 2.64*
10.00 ± 5.19
AEP + NS
23.98 ± 4.90
25.40 ± 3.37
13.00 ± 1.92
Taurine + AEP
18.46 ± 2.27
14.55 ± 3.61*
9.55 ± 2.04
GABA + AEP
17.45 ± 1.81*
15.72 ± 7.38*
10.12 ± 2.12
Activities of SOD and GSH-Px in PTZ-induced acute epileptic state rats
Test result of SOD activity of the hippocampus and cerebral cortex of every group
Hippocampus (U/mg protein)
Cerebral cortex (U/mg protein)
Control + NS
24.27 ± 1.83*
18.22 ± 0.31
AEP + NS
20.14 ± 0.56
16.68 ± 1.96
Taurine + AEP
23.86 ± 1.73*
22.49 ± 2.09
GABA + AEP
23.16 ± 1.38*
21.97 ± 4.93
Test result of GSH-Px activity of the hippocampus and cerebral cortex of every group
Hippocampus (U/mg protein)
Cerebral cortex (U/mg protein)
Control + NS
26.21 ± 1.30*
32.14 ± 10.97*
AEP + NS
14.55 ± 2.07
13.90 ± 2.52
Taurine + AEP
28.17 ± 3.11*
36.68 ± 12.90*
GABA + AEP
26.12 ± 2.97*
37.65 ± 8.47*
Taurine is widely applied as an antioxidant or dietary supplement and is demonstrated to reduce significantly MDA levels in the serum and/or tissue . GABA is widely applied as an additive . Similarly, it is reported that Glu and Asp can prevent cardiac toxicity by alleviating oxidative stress .
Our results demonstrate that taurine or GABA reacts rapidly with MDA, and the reaction of Glu or Asp with MDA under supraphysiological conditions is difficult (Figures 1 and 2). The observations are consistent with the hypothesis that amino acids act as a sacrificial nucleophile, trapping reactive intermediates [36, 37]. Scavenging carbonyl function of four amino acids is shown in Figures 4 and 5. The strong inhibition effect of taurine and GABA on MDA and the fast formation of products show that taurine and GABA can react rapidly; however, the reaction of Glu or Asp with MDA is very weak under supraphysiological conditions due to its different chemical structures (Table 1, Figure 3). In addition, if it is thought of four amino acids in the context of the neural system, taurine and GABA are important inhibitory amino acid neurotransmitters, and Glu and Asp are significant excitatory amino acid neurotransmitters. Glu and Asp uptake induce excitotoxicity, thereby causing oxidative stress and further lipid peroxidation . MDA-related carbonyl stress injures neurons by triggering Ca2+ influx and calcium overload . Indeed, it is possible that only taurine and GABA prevent neurons from damage with anticarbonylation toxic function besides inhibiting neuron superexcitation . Also, studies  thought GABA treatment could prolong survival of transplanted β cells. MDA was considered to suppress cerebral function by breaking homeostasis between the excitation and inhibition . However, MDA content in the brain tissue is enhanced dramatically to as high as 10 to 30 μm under pathophysiological conditions , such as aging and neurodegenerative diseases [44, 45]. Thus, in vivo system, these results are considered if taurine and GABA can scavenge active carbonyl besides MDA in neural tissues or cells such as the epileptic focus  accumulated chemicals on their membrane. Here, taking AEP for example, the neuroprotective effects of taurine and GABA are investigated on peroxidation of the AEP model.
Our results have shown that MDA concentration was elevated and SOD activity decreased in the AEP rats. After administration of taurine and GABA in the cerebral cortex and hippocampus of AEP rats, the level of MDA was decreased significantly (Table 2), and the activities of SOD and GSH-Px were increased significantly. However, two administration groups had no statistical difference from each other as well as with the normal group (Tables 3 and 4). The result indicated that the peripherally administered taurine and GABA can scavenge free radicals and protect the tissue against active carbonyl harm.
Our study in vitro demonstrates that four amino acid neurotransmitters inhibit the formation of reactive carbonyl intermediates during oxidative stress and react with MDA to form different conjugated complexes. These data illustrate taurine's or GABA's strong function to scavenge endogenous and/or further extrinsic unsaturated reactive carbonyls. In comparison, the scavenging function of Glu or Asp is very weak when reacting with MDA. The molecular mechanism of taurine's or GABA's inhibition and the investigation of its neuroprotective effects in vivo may prove useful for limiting the increased chemical modification of tissue proteins and cells on oxidative stress.
We gratefully acknowledge the support to this research from the Chinese 973 Project (no. 2010CB933903), the Key Scientific Research Fund of Hunan Provincial Education Department (11A030), Hunan Natural Scientific Foundation (12JJ6060), the Hunan Science and Technology Project (2012SK3105), and China Postdoctoral Science Foundation (2012M20980).
- Aldini G, Dalle-Donne I, Facino RM, Milzani A, Carini M: Intervention strategies to inhibit protein carbonylation by lipoxidation-derived reactive carbonyls. Med Res Rev 2007, 27: 817–868. 10.1002/med.20073View ArticleGoogle Scholar
- Baillet A, Chanteperdrix V, Trocmé C, Casez P, Garrel C, Besson G: The role of oxidative stress in amyotrophic lateral sclerosis and Parkinson's disease. Neurochem Res 2010, 35: 1530–1537. 10.1007/s11064-010-0212-5View ArticleGoogle Scholar
- Costello DJ, Delanty N: Oxidation injury in epilepsy: potential for antioxidant therapy? Expert Rev Neurother 2004, 4: 541–553. 10.1586/14737126.96.36.1991View ArticleGoogle Scholar
- Gabbita SP, Lovell MA, Markesbery WR: Increased nuclear DNA oxidation in the brain in Alzheimer's disease. J Neurochem 1998, 71: 2034–2040.View ArticleGoogle Scholar
- Smith MA, Hirai K, Hsiao K, Pappolla MA, Harris PL, Siedlak SL, Tabaton M, Perry G: Amyloid-b deposition in Alzheimer transgenic mice is associated with oxidative stress. J Neurochem 1998, 70: 2212–2215.View ArticleGoogle Scholar
- Gironi M, Bianchi A, Russo A, Alberoni M, Ceresa L, Angelini A, Cursano C, Mariani E, Nemni R, Kullmann C, Farina E: Martinelli Boneschi F: Oxidative imbalance in different neurodegenerative diseases with memory impairment. Neurodegener Dis 2011, 8: 129–137. 10.1159/000319452View ArticleGoogle Scholar
- Esterbauer H, Schaur RJ, Zollner H: Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radical Biol Med 1991, 11: 81–128. 10.1016/0891-5849(91)90192-6View ArticleGoogle Scholar
- Dalle-Donne I, Giustarini D, Colombo R, Rossi R, Milzani A: Protein carbonylation in human diseases. Trends Mol Med 2003, 9: 169–176. 10.1016/S1471-4914(03)00031-5View ArticleGoogle Scholar
- Slatter DA, Murray M, Bailey AJ: Formation of a dihydropyridine derivative as a potential cross-link derived from malondialdehyde in physiological systems. FEBS Lett 1998, 421: 180–184. 10.1016/S0014-5793(97)01554-8View ArticleGoogle Scholar
- Casado A, Encarnación López-Fernández M, Concepción Casado M, de La Torre R: Lipid peroxidation and antioxidant enzyme activities in vascular and Alzheimer dementias. Neurochem Res 2008, 33: 450–458. 10.1007/s11064-007-9453-3View ArticleGoogle Scholar
- Tomic S, Brkic S, Maric D, Mikic AN: Lipid and protein oxidation in female patients with chronic fatigue syndrome. Arch Med Sci 2012, 8(5):886–891.View ArticleGoogle Scholar
- Miyata T, Ueda Y, Saito A, Kurokawa K: Carbonyl stress and dialysis-related amyloidosis. Nephrol Dial Transplant 2000, 15: 25–28.View ArticleGoogle Scholar
- Yin D: Biochemical basis of lipofuscin, ceroid, and age pigment-like fluorophores. Free Radical Biol Med 1996, 21: 871–888. 10.1016/0891-5849(96)00175-XView ArticleGoogle Scholar
- Requena JR, Fu MX, Ahmed MU, Jenkins AJ, Lyons TJ, Baynes JW: Quantification of malondialdehyde and 4-hydroxynonenal adducts to lysine residues in native and oxidized human low-density lipoprotein. Biochem J 1997, 322: 317–325.View ArticleGoogle Scholar
- Bonnes-Taourel D, Guérin MC, Torreilles J: Is malonaldehyde a valuable indicator of lipid peroxidation. Biochem Pharmacol 1992, 44: 985–988. 10.1016/0006-2952(92)90132-3View ArticleGoogle Scholar
- Andersen JK: Oxidative stress in neurodegeneration: cause or consequence? Nat Rev Neurosci 2004, 5: S18-S25.View ArticleGoogle Scholar
- Browne SE, Ferrante RJ, Beal MF: Oxidative stress in Huntington's disease. Brain Pathol 1999, 9: 147–163.View ArticleGoogle Scholar
- Hall ED, Andrus PK, Oostveen JA, Fleck TJ, Gurney ME: Relationship of oxygen radical-induced lipid peroxidative damage to disease onset and progression in a transgenic model of familial ALS. J Neurosci Res 1998, 53: 66–77. 10.1002/(SICI)1097-4547(19980701)53:1<66::AID-JNR7>3.0.CO;2-HView ArticleGoogle Scholar
- Gustaw-Rothenberg K, Kowalczuk K, Stryjecka-Zimmer M: Lipids peroxidation markers in Alzheimer's disease and vascular dementia. Geriatr Gerontol Int 2010, 10: 161–166.Google Scholar
- Greilberger J, Koidl C, Greilberger M, Lamprecht M, Schroecksnadel K, Leblhuber F, Fuchs D, Oettl K: Malondialdehyde, carbonyl proteins and albumin-disulphide as useful oxidative markers in mild cognitive impairment and Alzheimer's disease. Free Radic Res 2008, 42: 633–638. 10.1080/10715760802255764View ArticleGoogle Scholar
- Medina-Hernández V, Ramos-Loyo J, Luquin S, Sánchez LF, García-Estrada J, Navarro-Ruiz A: Increased lipid peroxidation and neuron specific enolase in treatment refractory schizophrenics. J Psychiatr Res 2007, 41: 652–658. 10.1016/j.jpsychires.2006.02.010View ArticleGoogle Scholar
- Keller JN, Mattson MP: Roles of lipid peroxidation in modulation of cellular signaling pathways, cell dysfunction, and death in the nervous system. Rev Neurosci 1998, 9: 105–116.Google Scholar
- Tabassum H, Parvez S, Rehman H, Banerjee BD, Raisuddin S: Catechin as an antioxidant in liver mitochondrial toxicity: inhibition of tamoxifen-induced protein oxidation and lipid peroxidation. J Biochem Molecul Toxicol 2007, 21: 110–117. 10.1002/jbt.20167View ArticleGoogle Scholar
- Alvarez JG, Storey BT: Taurine, hypotaurine, epinephrine and albumin inhibit lipid peroxidation in rabbit spermatozoa and protect against loss of motility. Biol Reprod 1983, 29: 548–555. 10.1095/biolreprod29.3.548View ArticleGoogle Scholar
- Cetin F, Dincer S, Ay R, Guney S: Systemic taurine prevents brain from lipopolysaccharide-induced lipid peroxidation in rats. Afr J Pharm Pharmacol 2012, 6: 1099–1105.Google Scholar
- Deng Y, He N, Xu L, Li X, Li S, Li Z, Liu H: A rapid scavenger of lipid peroxidation product malondialdehyde: new perspective of taurine. Adv Sci Lett 2011, 4: 442–448. 10.1166/asl.2011.1219View ArticleGoogle Scholar
- Hayakawa K, Kimura M, Kasaha K, Matsumoto K, Sansawa H, Yamori Y: Effect of a γ-aminobutyric acid-enriched dairy product on the blood pressure of apontaneously hypertensive and normotensive Wistar-Kyoto rats. Brit J Nutr 2004, 92: 411–417. 10.1079/BJN20041221View ArticleGoogle Scholar
- Leventhal AG, Wang Y, Pu M, Zhou Y, Ma Y: GABA and its agonists improved visual cortical function in senescent monkeys. Science 2003, 300(5620):812–815. 10.1126/science.1082874View ArticleGoogle Scholar
- Hua T, Kao C, Sun Q, Li X, Zhou Y: Decreased proportion of GABA neurons accompanies age-related degradation of neuronal function in cat striate cortex. Brain Res Bull 2008, 75: 119–125. 10.1016/j.brainresbull.2007.08.001View ArticleGoogle Scholar
- Song H, Xu X, Wang H, Wang H, Tao Y: Exogenous γ-aminobutyric acid alleviates oxidative damage caused by aluminium and proton stresses n barley seedlings. J Sci Food Agric 2010, 90: 1410–1416. 10.1002/jsfa.3951View ArticleGoogle Scholar
- Sivakumar R, Babu PVA, Shyamaladevi CS: Asp and Glu prevents isoproterenol-induced cardiac toxicity by alleviating oxidative stress in rats. Exp Toxicol Pathol 2011, 63: 137–142. 10.1016/j.etp.2009.10.008View ArticleGoogle Scholar
- Kikugawa K, Beppu M: Involvement of lipid oxidative products in the formation of fluorescent and cross-linked proteins. Chem Phys Lipids 1987, 44: 277–296. 10.1016/0009-3084(87)90054-5View ArticleGoogle Scholar
- Deng Y, Xu L, Zeng X, Li Z, Qin B, He N: New perspective of GABA as an inhibitor of formation of advanced lipoxidation end-products: it's interaction with malondiadehyde. J Biomed Nanotechnol 2010, 6: 318–324. 10.1166/jbn.2010.1130View ArticleGoogle Scholar
- Erdtmann-Vourliotis M, Riechert U, Maye P, Grecksch G, Hollt V: Pentylenetetrazole (PTZ)-induced c-fos expression in the hippocampus of kindled rats is suppressed by concomitant treatment with naloxone. Brain Res 1998, 792: 299–308. 10.1016/S0006-8993(98)00159-0View ArticleGoogle Scholar
- Fathollahi Y, Motamedi F, Semnanian S, Zardoshti M: Examination of persistent effects of repeated administration of pentylenetetrazol on rat hippocampal CA1: evidence from in vitro study on hippocampal slices. Brain Res 1997, 758: 92–98. 10.1016/S0006-8993(97)00164-9View ArticleGoogle Scholar
- Onorato JM, Jenkins AJ, Thorpe SR, Baynes JW: Pyridoxamine, an inhibitor of advanced glycation reactions, also inhibits advanced lipoxidation reactions. J Biol Chem 2000, 275: 21177–21184. 10.1074/jbc.M003263200View ArticleGoogle Scholar
- Fang C, Peng M, Li G, Tian J, Yin D: New functions of glucosamine as a scavenger of the lipid peroxidation product malondialdehyde. Chem Res Toxicol 2007, 20: 947–953. 10.1021/tx700059bView ArticleGoogle Scholar
- Zhang F, Mao Y, Qiao H, Jiang H, Zhao H, Chen X, Tong L, Sun X: Protective effects of taurine against endotoxin-induced acute liver injury after hepatic ischemia reperfusion. Amino acids 2010, 38: 237–245. 10.1007/s00726-009-0233-zView ArticleGoogle Scholar
- Cai J, Chen J, He H, Yin Z, Zhu Z, Yin D: Carbonyl stress: malondialdehyde induces damage on rat hippocampal neurons by disturbance of Ca(2+) homeostasis. Cell Biol Toxicol 2009, 25: 435–445. 10.1007/s10565-008-9097-3View ArticleGoogle Scholar
- Bernard C, Cossart R, Hirsch JC, Esclapez M, Ben-Ari Y: What is GABAergic inhibition? How is it modified in epilepsy? Epilepsia 2000, 41(Suppl 6):890–895.Google Scholar
- Tian J, Dang HL, Kaufman D: Combining antigen-based therapy with GABA treatment synergistically prolongs survival of transplanted ß-cells in diabetic NOD mice. Plos One 2011, 6: e25337. 10.1371/journal.pone.0025337View ArticleGoogle Scholar
- Li F, Yang Z, Lu Y, Wei Y, Wang J, Yin D, He R: Malondialdehyde suppresses cerebral function by breaking homeostasis between excitation and inhibition in turtle Trachemys scripta . Plos One 2010, 12: e15325.View ArticleGoogle Scholar
- Gilgun-Sherki Y, Melamed E, Offen D: Oxidative stress induced-neurodegenerative diseases: the need for antioxidants that penetrate the blood brain barrier. Neuropharmacology 2001, 40: 959–975. 10.1016/S0028-3908(01)00019-3View ArticleGoogle Scholar
- Gil P, Farinas F, Casado A, Lopez-Fernandez E: Malondialdehyde: a possible marker of ageing. Gerontology 2002, 48: 209–214. 10.1159/000058352View ArticleGoogle Scholar
- Leutner S, Eckert A, Muller WE: ROS generation, lipid peroxidation and antioxidant enzyme activities in the aging brain. J Neural Transm 2001, 108: 955–967. 10.1007/s007020170015View ArticleGoogle Scholar
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