Skip to main content
Log in

Reversal of propoxur-induced impairment of memory and oxidative stress by 4′-chlorodiazepam in rats

  • ORIGINAL ARTICLE
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

Carbamate pesticides like propoxur have been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. The present study was designed to explore the modulation of the effects of propoxur over cognitive function by progesterone (PROG) and 4′-chlorodiazepam (4CD). Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus, transfer latency (TL) on a plus maze and spatial navigation test on Morris water maze. Oxidative stress was assessed by examining brain malondialdehyde (MDA) and reduced glutathione (GSH) levels and catalase (CAT) activity. A significant reduction in SDL and prolongation of TL and spatial navigation test was found for the propoxur (10 mg/kg/d; p.o.) treated group at weeks 6 and 7 as compared with control. One-week treatment with 4CD (0.5 mg/kg/d; i.p.) antagonized the effect of propoxur on SDL, spatial navigation test as well as TL; whereas, PROG failed to modulate this effect at a dose of 15 mg/kg/d, i.p. Propoxur produced a statistically significant increase in the brain MDA levels and decrease in the brain GSH levels and CAT activity. Treatment with 4CD at the above dose attenuated the effect of propoxur on oxidative stress whereas PROG (15 mg/kg/d; i.p.) failed to influence the same. The results of the present study thus show that 4-CD has the potential to attenuate cognitive dysfunction and oxidative stress induced by toxicants like propoxur in the brain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Aslan M, Ozben T (2004) Reactive oxygen and nitrogen species in Alzheimer's disease. Curr Alzheimer Res 1:111–119

    Article  CAS  PubMed  Google Scholar 

  • Banerjee BD, Seth V, Bhattacharya A, Pasha ST, Chakrabory AK (1999) Biochemical effects of some pesticides on lipid peroxidation and free radical scavengers. Toxicol Lett 107:33–47

    Article  CAS  PubMed  Google Scholar 

  • Baulieu EE, Robel P (1990) Neurosteroids: a new brain function. J Steroid Biochem Mol Biol 37:395–403

    Article  CAS  PubMed  Google Scholar 

  • Bimonte-Nelson HA, Francis KR, Umphlet CD, Granholm AC (2006) Progesterone reverses the spatial memory enhancements initiated by tonic and cyclic oestrogen therapy in middle-aged ovariectomized female rats. Eur J NeuroSci 24:229–242

    Article  PubMed  Google Scholar 

  • Bucolo C, Drago F, Lin LR, Reddy VN (2005) Neuroactive steroids protect retinal pigment epithelium against oxidative stress. NeuroReport 16:1203–1207

    Article  CAS  PubMed  Google Scholar 

  • Clairborne A (1985) Catalase activity. In: Greenwald RA (ed) Handbook of methods for oxygen radical research. CRC, Boca Raton, pp 293–284

    Google Scholar 

  • Da Cunha C, Huang CH, Walz R, Dias M, Koya R, Bianchin M, Pereira ME, Izquierdo I, Medina JH (1991) Memory facilitation by post-training intraperitoneal, intracerebroventricular and intra-amygdala injection of Ro 5-4864. Brain Res 544:133–136

    Article  PubMed  Google Scholar 

  • Dhingra D, Parle M, Kulkarni SK (2003) Effect of combination of insulin with dextrose, D(-) fructose and diet on learning and memory in mice. Ind J Pharmacol 35:151–156

    CAS  Google Scholar 

  • Djebaili M, Hoffman SW, Stein DG (2004) Allopregnanolone and progesterone decrease cell death and cognitive deficits after a contusion of the rat pre-frontal cortex. Neuroscience 123:349–359

    Article  CAS  PubMed  Google Scholar 

  • Do-Rego JL, Mensah-Nyagan AG, Feuilloley M, Ferrara P, Pelletier G, Vaudry H (1998) The endozepine triakontatetraneuropeptide diazepam-binding inhibitor [17–50] stimulates neurosteroid biosynthesis in the frog hypothalamus. Neuroscience 83:555–570

    Article  CAS  PubMed  Google Scholar 

  • Dowla HA, Panemanglore M, Byers ME (1996) Comparative inhibition of enzymes of human erythrocytes and plasma in vitro by agricultural chemicals. Arch Enviorn Contam Toxicol 31:107–114

    Article  CAS  Google Scholar 

  • Drummer HL, Woolley DE (1997) Toxicokinetics of Ro 5-4864, lindane and picrotoxin compared. Pharmacol Biochem Behav 38:235–242

    Article  Google Scholar 

  • El-Bakri NK, Islam A, Zhu S, Elhassan A, Mohammed A, Winblad B, Adem A (2004) Effects of estrogen and progesterone treatment on rat hippocampal NMDA receptors: relationship to Morris water maze performance. J Cell Mol Med 8:537–544

    Article  CAS  PubMed  Google Scholar 

  • Ellman GL (1959) Tissue sulphydryl groups. Arch Biochem Biophys 82:70–77

    Article  CAS  PubMed  Google Scholar 

  • Eraslan G, Kanbur M, Silici S, Cem Liman B, Altinordulu S, Soyer Sarica Z (2009) Evaluation of protective effect of bee pollen against propoxur toxicity in rat. Ecotoxicol Environ Saf 72:931–937

    Article  CAS  PubMed  Google Scholar 

  • File SE (1984) Modification of seizures elicited by the benzodiazepine Ro 5-3663—a comparison with picrotoxin. J Pharm Pharmacol 36:837–840

    CAS  PubMed  Google Scholar 

  • Flood JF, Morley JE, Roberts E (1992) Memory-enhancing effects in male mice of pregnenolone and steroids metabolically derived from it. Proc Natl Acad Sci 89:1567–1571

    Article  CAS  PubMed  Google Scholar 

  • Flood JF, Morley JE, Roberts E (1995) Pregnenolone sulfate enhances post-training memory processes when injected in very low doses into limbic system structures: the amygdala is by far the most sensitive. Proc Natl Acad Sci 92:10806–10810

    Article  CAS  PubMed  Google Scholar 

  • Frautschy SA, Hu W, Kim P, Miller SA, Chu T, Harris-White ME, Cole GM (2001) Phenolic anti-inflammatory, antioxidant reversal of Abeta-induced cognitive deficits and neuropathology. Neurobiol Aging 22:993–1005

    Article  CAS  PubMed  Google Scholar 

  • Grigorova M, Sherwin BB (2006) No differences in performance on test of working memory and executive functioning between healthy elderly postmenopausal women using or not using hormone therapy. Climacteric 9:181–194

    Article  CAS  PubMed  Google Scholar 

  • Itoh J, Nabeshima T, Kameyama T (1990) Utility of an elevated plus-maze for the evaluation of memory in mice: effect of nootropics, scopolamine and electroconvulsive shock. Psychopharmacology 101:27–33

    Article  CAS  PubMed  Google Scholar 

  • Izquierdo I, Medina JH, Da-Cunha C, Wolfman C, Jerusalinsky D, Ferreira MB (1991) Memory modulation by brain benzodiazepines. Braz J Med Biol Res 24:865–881

    CAS  PubMed  Google Scholar 

  • Sharma M, Gupta YK (2002) Chronic treatment with trans resveratrol prevents intracerebroventricular streptozotocin induced cognitive impairment and oxidative stress in rats. Life Sci 71:2489–2498

    Article  CAS  PubMed  Google Scholar 

  • Izquierdo I, Fin C, Schmitz PK, Da Silva RC, Jerusalinsky D, Quillfeldt JA, Ferreira MB, Medina JH, Bazan NG (1995) Memory enhancement by intrahippocampal, intraamygdala, orintraentorhinal infusion of platelet-activating factor measured in an inhibitory avoidance task. Proc Natl Acad Sci 92:5041–5057

    Article  Google Scholar 

  • Jo DH, Abdallah MA, Young J, Baulieu EE, Robel P (1989) Pregnenolone, dehydroepiandrosterone and their sulfate and fatty acid esters in the rat brain. Steroids 54:287–297

    Article  CAS  PubMed  Google Scholar 

  • Johansson IM, Birznievce V, Lindblad C, Olsson T, Backstom T (2002) Allopregnanolone inhibits learning in the morris water maze. Brain Res 934:125–131

    Article  CAS  PubMed  Google Scholar 

  • Joshi H, Parle M (2006) Brahmi rasayana improves learning and memory in mice. Evid-Based Compl Alt 3:79–85

    Article  Google Scholar 

  • Jung-Testas I, Renoir JM, Bugnard H, Greene GL, Baulieu EE (1992) Demonstration of steroid hormone receptors and steroid action in primary cultures of rat glial cells. J steroid Biochem Mol Biol 41:621–631

    Article  CAS  PubMed  Google Scholar 

  • Korneyev A, Pan BS, Romeo PE, Guidotti A, Costa E (1993) Stimulation on brain pregnenolone synthesis by mitochondrial diazepam binding inhibitor receptor ligands in vivo. J Neurochem 61:1515–1524

    Article  CAS  PubMed  Google Scholar 

  • Korol DL, Malin EL, Borden KA, Busby RA, Couper-Leo J (2004) Shifts in preferred learning strategy across the estrous cycle in female rats. Horm Behav 45:330–338

    Article  CAS  PubMed  Google Scholar 

  • Kulkarni SK, Reddy DS (1995) Neurosteroids: a new class of neuromodulators. Drugs Today 31:433–455

    CAS  Google Scholar 

  • Lacor P, Gandolfo P, Tonon MC, Brault E, Dalibert I, Schumacher M, Benavides J, Ferzaz B (1999) Regulation of the expression of peripheral benzodiazepine receptors and their endogenous ligands during rat sciatic nerve degeneration and regeneration: a role for PBR in neurosteroidogenesis. Brain Res 815:70–80

    Article  CAS  PubMed  Google Scholar 

  • Lagrange A (2006) Dancing the delta shuttle: neurosteroids regulate GABAA receptor expression. Epilepsy Currents 6:14–17

    Article  PubMed  Google Scholar 

  • Leskiewicz M, Regulska M, Budziszewska B, Jantas D, Jaworska-Feil L, Basta-Kaim A, Kubera M, Jagla G, Nowak W, Lason W (2008) Effects of neurosteroids on hydrogen peroxide- and staurosporine-induced damage of human neuroblastoma SH-SY5Y cells. J Neurosci Res 86:1361–1370

    Article  CAS  PubMed  Google Scholar 

  • Majewska MD (1992) Neurosteroids: endogenous bimodal modulators of the GABAA receptor. Mechanism of action and physiological significance. Prog Neurobiol 38:379–395

    Article  CAS  PubMed  Google Scholar 

  • Maki PM, Zonderman AB, Resnick SM (2001) Enhanced verbal memory in nondemented elderly women receiving hormone-replacement therapy. Am J Psychiatry 158:227–233

    Article  CAS  PubMed  Google Scholar 

  • Maran E, Fernández M, Barbieri P, Font G, Ruiz MJ (2009) Effects of four carbamate compounds on antioxidant parameters. Ecotoxicol Environ Saf 72:922–930

    Article  CAS  PubMed  Google Scholar 

  • Marselli L, Trincavelli L, Santangelo C, Lupi R, Del Guerra S, Boggi U, Falleni A, Gremigni V, Mosca F, Martini C, Dotta F, Di Mario U, Del Prato S, Marchetti P (2004) The role of peripheral benzodiazepine receptors on the function and survival of isolated human pancreatic islets. Eur J Endocrinol 151:207–214

    Article  CAS  PubMed  Google Scholar 

  • Marx CE, Trost WT, Shampine LJ, Stevens RD, Hulette CM, Steffens DC, Ervin JF, Butterfield MI, Blazer DG, Massing MW, Lieberman JA (2006) The Neurosteroid allopregnanolone is reduced in prefrontal cortex in Alzheimer's disease. Biol Psychiatry 60:1287–1294

    Article  CAS  PubMed  Google Scholar 

  • Maurice T, Phan VL, Urani A, Guillemain I (2001) Differential involvement of the sigma (1) receptor in the anti-amnesic effect of neuroactive steroids, as demonstrated using an in vivo antisense strategy in the mouse. Br J Pharmacol 134:1731–1741

    Article  CAS  PubMed  Google Scholar 

  • Miachon S, Augier S, Jouvenet M, Boucher P, Vallon JJ (2001) Nutritional parameters modify muricidal behavior of male Wistar rats: preventive effects of amino acids and 4' Cl diazepam. Life Sci 69:2745–2757

    Article  CAS  PubMed  Google Scholar 

  • Mondadori C, Hengerer B, Ducret T, Borkowoski J (1994) Delayed emergence of effects of memory-enhancing drugs: Implications for the dynamics of long-term memory. Proc Natl Acad Sci USA 91:2041–2045

    Article  CAS  PubMed  Google Scholar 

  • Naidu PS, Singh A, Kulkarni KS (2004) Quercitin and reserpine induced orofacial dyskinesia. Pharmacology 70:59–67

    Article  CAS  PubMed  Google Scholar 

  • Okhawa H, Ohishi N, Yagi K (1979) Assay of lipid peroxides in animal tissue by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  Google Scholar 

  • Parle M, Dhingra D (2003) Ascorbic Acid: a promising memory-enhancer in mice. J Pharm Sci 93:129–135

    Article  CAS  Google Scholar 

  • Reddy DS, Kulkarni SK (1997) Neuroprotective effects of neurosteroids against hypoxic neurotoxicity in naive and benzodiazepine inverse agonist FG 7142-treated mice. Indian J Pharmacol 29:381–392

    CAS  Google Scholar 

  • Reddy DS, Rogawski MA (2009) Neurosteroid replacement therapy for catamenial epilepsy. Neurotherapeutics 6:392–401

    Article  CAS  PubMed  Google Scholar 

  • Roof RL, Hoffman SW, Stein DG (1997) Progesterone protects against lipid peroxidation following traumatic brain injury in rats. Mol Chem Neuropathol 31:1–11

    Article  CAS  PubMed  Google Scholar 

  • Rupprecht R, Holsboer F (1999) Neuropsychopharmacological properties of neuroactive steroids. Steroids 64:83–91

    Article  CAS  PubMed  Google Scholar 

  • Sahaya K, Mahajan P, Mediratta PK, Ahmed RS, Sharma KK (2007) Reversal of lindane-induced impairment of step-down passive avoidance and oxidative stress by neurosteroids in rats. Toxicol 239:116–126

    Article  CAS  Google Scholar 

  • Schmuck G, Mihail F (2004) Effect of the carbamates fenoxycarb, propamacarb and propoxur on energy supply, glucose utilization and SH-groups in neuron. Arch Toxicol 78:330–337

    Article  CAS  PubMed  Google Scholar 

  • Schumacher M, Guennoun R, Robel P, Baulieu EE (1997) Neurosteroids in the hippocampus: neuronal plasticity and memory. Stress 2:65–78

    Article  CAS  PubMed  Google Scholar 

  • Shirling D, Ashby JP, Baird JD (1981) Effect of progesterone on lipid metabolism in the intact rat. J Endocrinol 90:285–294

    Article  CAS  PubMed  Google Scholar 

  • Shirling D, Ashby JP, Baird JD (1983) A direct anabolic effect of progesterone in the intact female rat. J Endocrinol 99:47–50

    Article  CAS  PubMed  Google Scholar 

  • Sliwinski A, Monnet FP, Schumacher M, Morin-Surun MP (2004) Pregnenolone sulfate enhances long-term potentiation in CA1 in rat hippocampus slices through the modulation of N-methyl-d-aspartate receptors. J Neurosci Res 78:691–701

    Article  CAS  PubMed  Google Scholar 

  • Smuldeas CJ, Bueters TJ, Van Kleef RG, Vijverberg HP (2003) Selective effects of carbamate pesticides on rat neuronal nicotinic acetylcholine and rat brain acetylcholinestrase. Toxicol Appl Pharmacol 193:139–146

    Article  Google Scholar 

  • Stoffel-Wagner B (2001) Neurosteroid metabolism in the human brain. Eur J Endocrinol 145:669–679

    Article  CAS  PubMed  Google Scholar 

  • Suke SG, Kumar A, Ahmed RS, Chakaraborti A, Tripathi AK, Mediratta PK, Banerjee BD (2006) Protective effect of Melatonin against propoxur induced oxidative stress and suppression of humoral immune support in rats. Ind J Pharmacol 44:312–315

    CAS  Google Scholar 

  • Sutcliffe JS, Marshall KM, Neill JC (2007) Influence of gender on working and spatial memory in the novel object recognition task in the rat. Behav Brain Res 177:117–125

    Article  CAS  PubMed  Google Scholar 

  • Tilson HA, Shaw S, Mclamb RL (1987) The effects of lindane and chlordecone on avoidance responding and seizure activity. Toxicol Appl Pharmacol 88:57–65

    Article  CAS  PubMed  Google Scholar 

  • Toth MJ, Poehlman ET, Matthews DE, Tchernof A, MacCoss MJ (2001) Effects of estradiol and progesterone on body composition, protein synthesis, and lipoprotein lipase in rats. Am J Physiol Endocrinol Metab 280:E496–E501

    CAS  PubMed  Google Scholar 

  • Tunez I, Munoz MC, Montilla P (2005) Treatment with dehydroepiandrosterone prevents oxidative stress induced by 3-nitropropionic acid in synaptosomes. Pharmacology 74:113–118

    CAS  PubMed  Google Scholar 

  • Veinbergs I, Mallory M, Sagara Y, Masliah E (2000) Vitamin E supplementation prevents spatial learning deficits and dendritic alterations in aged apolipoprotein E-deficient mice. Eur J NeuroSci 12:4541–4546

    CAS  PubMed  Google Scholar 

  • Vongher JM, Frye CA (1999) Progesterone in conjunction with estradiol has neuroprotective effects in an animal model of neurodegeneration. Pharmacol Biochem Behav 64:777–785

    Article  CAS  PubMed  Google Scholar 

  • Weill-Engerer SB, David JP, Sazdovitch VR, Liere P, Eychenne B, Pianos A, Schumacher M, Delacourte A, Baulieu EE, Akwa Y (2002) Neurosteroid quantification in human brain regions: comparison between Alzheimer's and nondemented patients. J Clin Endocrinol Metab 87:5138–5143

    Article  CAS  PubMed  Google Scholar 

  • Woolley D, Zimmer L, Zuheir H, Swanson K (1984) Do some insecticides and heavy metals produce long-term potentiation in the limbic system? In: Narahashi T (ed) Cellular and molecular neurotoxicology. Raven Press, New York, pp 45–69

    Google Scholar 

  • Yonker JE, Adolfsson R, Eriksson E, Hellstrand M, Nilsson LG, Herlitz A (2006) Verified hormone therapy improves episodic memory performance in healthy postmenopausal women. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 13:291–230

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gobind Rai Garg.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mehta, K.D., Garg, G.R., Mehta, A.K. et al. Reversal of propoxur-induced impairment of memory and oxidative stress by 4′-chlorodiazepam in rats. Naunyn-Schmied Arch Pharmacol 381, 1–10 (2010). https://doi.org/10.1007/s00210-009-0475-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-009-0475-z

Keywords

Navigation