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Opposite effects of α-lipoic acid on antioxidation and long-term potentiation in control and chronically lead-exposed rats

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Abstract

Among the developmental changes identified in rats exposed to lead are impairments in long-term potentiation (LTP) in the hippocampus and changes in the levels of reactive oxygen species (ROS) in cells and some soft tissues. α-Lipoic acid (LA) has been reported to be highly effective in improving the thiol capacity of the cells and in reducing lead-induced oxidative stress. To explore the effects of LA on LTP in chronically lead-exposed rats and the relationship between ROS and LTP in both control and lead-exposed rats, we have compared LTP and oxidative stress parameters in groups of lead-exposed and control rats with or without LA treatment (10, 25, 50, and 100 mg/kg through intraperitoneal injection). The capacity of LA to decrease hippocampal lead levels in lead-exposed rats was examined. We found that LA had no effects in decreasing the level of lead in the hippocampus, but it did appear to have both antioxidant properties and a reparatory effect on LTP amplitude in rats developmentally exposed to lead for 2 weeks following birth. Interestingly, bell-shaped dose-response curves emerged. In the lower LA dosage groups (10, 25 mg/kg LA), there was an increasing LTP amplitude. The strongest protective effect in terms of the induction and amplitude of LTP in the lead-exposed group with at 25 mg/kg LA; when higher dosages were applied (50, 100 mg/kg LA), the LTP amplitude decreased as compared to the 25 mg/kg LA treatment group. The administration of LA to control animals resulted in a significant impairment of LTP amplitude, with the 100 mg/kg LA treatment having harmful effects on the oxidative parameters. These differential effects of LA on LTP in control and lead-exposed rats may be due to the different redox status of the control and lead-exposed rats.

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Abbreviations

EPSPs:

excitatory postsynaptic potentials

GSH:

glutathione

LA:

lipoic acid

LTP:

long-term potentiation

MDA:

malondialdehyde

ROS:

reactive oxygen species

T-SOD:

total superoxide dismutase

References

  • Adonaylo VN, Oteiza PI (1999) Lead intoxication: antioxidant defenses and oxidative damage in rat brain. Toxicology 135:77–85

    Article  PubMed  CAS  Google Scholar 

  • Biewenga GP, Haenen GR, Bast A (1997) The pharmacology of the antioxidant lipoic acid. Gen Pharmacol 29:315–331

    PubMed  CAS  Google Scholar 

  • Café C, Torri C, Marzatico F (1993) Cellular and molecular events of ischemic brain damage. Funct Neurol 8:121–133

    PubMed  Google Scholar 

  • Cai L, Ruan DY, Xu YZ, Liu Z, Meng XM, Dai XQ (2001) Effects of lead exposure on long-term potentiation induced by 2-deoxy-D-glucose in area CA1 of rat hippocampus in vitro. Neurotoxicol Teratol 23:481–487

    Article  PubMed  CAS  Google Scholar 

  • Esterbauer H (1982) Aldehyde products of lipid peroxidation. In: Rien DCH, Slater TF (eds) Free radicals, lipid peroxidation and cancer. Academic Press, London, pp 101–128

    Google Scholar 

  • Farr SA, Poon HF, Dogrukol-Ak D, Drake J, Banks WA, Eyerman E, Butterfield DA, Morley JE (2003) The antioxidants alpha-lipoic acid and N-acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice. J Neurochem 84:1173–1183

    Article  PubMed  CAS  Google Scholar 

  • Flora SJ, Pande M, Kannan GM, Mehta A (2004) Lead induced oxidative stress and its recovery following co-administration of melatonin or N-acetylcysteine during chelation with succimer in male rats. Cell Mol Biol (Noisy-le-grand) 50: Online Pub OL543–551

  • Fracasso ME, Perbellini L, Solda S, Talamini G, Franceschetti P (2002) Lead induced DNA strand breaks in lymphocytes of exposed workers: role of reactive oxygen species and protein kinase C. Mutat Res 515:159–169

    PubMed  CAS  Google Scholar 

  • Gurer H, Ozgunes H, Oztezcan S, Ercal N (1999) Antioxidant role of alpha-lipoic acid in lead toxicity. Free Radic Biol Med 27:75–81

    Article  PubMed  CAS  Google Scholar 

  • Gutteridge JM (1995) Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem 41:1819–1828

    PubMed  CAS  Google Scholar 

  • Kamsler A, Segal M (2004) Hydrogen peroxide as a diffusible signal molecule in synaptic plasticity. Mol Neurobiol 29:167–178

    Article  PubMed  CAS  Google Scholar 

  • Klann E (1998) Cell-permeable scavengers of superoxide prevent long-term potentiation in hippocampal area CA1. J Neurophysiol 80:452–457

    PubMed  CAS  Google Scholar 

  • Klann E, Roberson ED, Knapp LT, Sweatt JD (1998) A role for superoxide in protein kinase C activation and induction of long-term potentiation. J Biol Chem 273:4516–4522

    Article  PubMed  CAS  Google Scholar 

  • Knapp LT, Klann E (2002a) Potentiation of hippocampal synaptic transmission by superoxide requires the oxidative activation of protein kinase C. J Neurosci 22:674–683

    PubMed  CAS  Google Scholar 

  • Knapp LT, Klann E (2002b) Role of reactive oxygen species in hippocampal long-term potentiation: contributory or inhibitory? Neurosci Res 70:1–7

    Article  CAS  Google Scholar 

  • Lander HM (1997) An essential role for free radicals and derived species in signal transduction. FASEB J 11:118–124

    PubMed  CAS  Google Scholar 

  • Lidsky TI, Schneider JS (2003) Lead neurotoxicity in children: basic mechanisms and clinical correlates. Brain 126:5–19

    Article  PubMed  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  • McGahon BM, Martin DS, Horrobin DF, Lynch MA (1999) Age-related changes in LTP and antioxidant defenses are reversed by an alpha-lipoic acid-enriched diet. Neurobiol Aging 20:655–664

    Article  PubMed  CAS  Google Scholar 

  • Meister A (1991) Glutathione deficiency produced by inhibition of its synthesis, and its reversal; applications in research and therapy. Pharmacol Ther 51:155–194

    Article  PubMed  CAS  Google Scholar 

  • Moini H, Packer L, Saris NE (2002) Antioxidant and prooxidant activities of alpha-lipoic acid and dihydrolipoic acid. Toxicol Appl Pharmacol 182:84–90

    Article  PubMed  CAS  Google Scholar 

  • National Research Council (1996) Guide for the care and use of laboratory animals. Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council, National Academy Press, Washington D.C.

  • Ni Z, Hou S, Barton CH, Vaziri ND (2004) Lead exposure raises superoxide and hydrogen peroxide in human endothelial and vascular smooth muscle cells. Kidney Int 66:2329–2336

    Article  PubMed  CAS  Google Scholar 

  • Packer L, Witt EH, Tritschler HJ (1995) alpha-Lipoic acid as a biological antioxidant. Free Radic Biol Med 19:227–250

    Article  PubMed  CAS  Google Scholar 

  • Pande M, Flora SJ (2002) Lead induced oxidative damage and its response to combined administration of alpha-lipoic acid and succimers in rats. Toxicology 177:187–196

    Article  PubMed  CAS  Google Scholar 

  • Reiter RJ (1995) Oxidative processes and antioxidative defense mechanisms in the aging brain. FASEB J 9:526–533

    PubMed  CAS  Google Scholar 

  • Ruan DY, Chen JT, Zhao C, Xu YZ, Wang M, Zhao WF (1998) Impairment of long-term potentiation and paired-pulse facilitation in rat hippocampal dentate gyrus following developmental lead exposure in vivo. Brain Res 806:196–201

    Article  PubMed  CAS  Google Scholar 

  • Ruan DY, Yan KF, Ge SY, Xu YZ, Chen JT, Wang M (2000) Effects of chronic lead exposure on short-term and long-term depression in area CA1 of the rat hippocampus in vivo. Chemosphere 41:165–171

    Article  PubMed  CAS  Google Scholar 

  • Sandhir R, Julka D, Gill KD (1994) Lipoperoxidative damage on lead exposure in rat brain and its implications on membrane bound enzymes. Pharmacol Toxicol 74:66–71

    PubMed  CAS  Google Scholar 

  • Saxena G, Flora SJ (2004) Lead-induced oxidative stress and hematological alterations and their response to combined administration of calcium disodium EDTA with a thiol chelator in rats. J Biochem Mol Toxicol 18:221–233

    Article  PubMed  CAS  Google Scholar 

  • Smith AR, Shenvi SV, Widlansky M, Suh JH, Hagen TM (2004) Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress. Curr Med Chem 11:1135–1146

    PubMed  CAS  Google Scholar 

  • Smythies J (2000) Redox aspects of signaling by catecholamines and their metabolites. Antioxid Redox Signal 2:575–583

    Article  PubMed  CAS  Google Scholar 

  • Solliway BM, Schaffer A, Pratt H, Yannai S (1996) Effects of exposure to lead on selected biochemical and haematological variables. Pharmacol Toxicol 78:18–22

    Article  PubMed  CAS  Google Scholar 

  • Sun Y, Oberley LW, Li Y (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34:497–500

    PubMed  CAS  Google Scholar 

  • Suzuki YJ, Forman HJ, Sevanian A (1997) Oxidants as stimulators of signal transduction. Free Radic Biol Med 22:269–285

    Article  PubMed  CAS  Google Scholar 

  • Tietze F (1969) Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem 27:502–522

    Article  PubMed  CAS  Google Scholar 

  • Vaziri ND, Ding Y (2001) Effect of lead on nitric oxide synthase expression in coronary endothelial cells: role of superoxide. Hypertension 37:223–226

    PubMed  CAS  Google Scholar 

  • Wang HL, Chen XT, Luo L, Lou ZY, Wang S, Chen JT, Wang M, Sun LG, Ruan DY (2006) Reparatory effects of nicotine on NMDA receptor-mediated synaptic plasticity in the hippocampal CA1 region of chronically lead-exposed rats. Eur J Neurosci 23:1111–1119

    Article  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the National Basic Research Program of China (No. 2002CB512907), the National Nature Science Foundation of China (No. 30630057; 30670554; 30670662; 30672290), Academia Sinica (No. KZCX3-SW-437), China Postdoctoral Science Foundation (No. 20060400719) and K.C. Wong Education Foundation of Hong Kong.

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Authors and Affiliations

  1. Department of Neurobiology and Biophysics, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230027, People’s Republic of China

    Hui-Li Wang, Xiang-Tao Chen, Shu-Ting Yin, Jin Liu, Ming-Liang Tang, Chuan-Yun Wu & Di-Yun Ruan

  2. Institute of Polar Environment, University of Science and Technology of China, Hefei, Anhui, 230027, People’s Republic of China

    Hui-Li Wang

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  1. Hui-Li Wang
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Correspondence to Di-Yun Ruan.

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Wang, HL., Chen, XT., Yin, ST. et al. Opposite effects of α-lipoic acid on antioxidation and long-term potentiation in control and chronically lead-exposed rats. Naunyn-Schmied Arch Pharmacol 378, 303–310 (2008). https://doi.org/10.1007/s00210-008-0307-6

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  • DOI: https://doi.org/10.1007/s00210-008-0307-6

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