To study the oxidative stress induced by lindane in epileptic rats brains and their modulation by neurosteroids

Krishna Tanwar, Pramod K. Mediratta, Basu D. Banerjee, Krishna K. Sharma

Abstract


Background: Lindane is pesticide has been shown to affect the nervous system adversely. Previous work has shown that lindane is proconvulsant and neurosteroids (NS) has been shown to be neuroprotective against lindane-induced convulsions. As the mechanisms of lindane in epileptogenesis is not completely understood. The present study was designed to investigate the oxidative stress parameters of lindane toxicity in epileptogenesis and their modulation by NS like allopregnanolone (AP), and 4ʹ-chlorodiazepam (4ʹ-CD) in pentylenetetrazole (PTZ) kindling methods.

Methods: Kindling was induced by injecting PTZ (30 mg/kg; s.c.) on alternate days i.e., 3 times in a week. Lindane was also administered (15 mg/kg p.o) on alternate days for 6 weeks. AP (2.5 mg/kg, intaperitoneal [i.p.]) and 4ʹ-CD (0.5 mg/kg, i.p.) single dose was given in kindled rats before lindane.

Results: Following per oral administration of lindane for 6 weeks produced significant oxidative stress in epileptic brain. There was an increase in brain malondialdehyde (MDA) level and decrease in reduced glutathione (GSH) levels. AP (2.5 mg/kg, i.p.) and 4ʹ-CD (0.5 mg/kg, i.p.) single dose administration were not able to reverse the effect of chronic exposure of lindane.

Conclusion: The result of the present study provides evidence that oxidative stress produced in the brain after chronic exposure of lindane may be the mechanism of epileptogenesis. Though NS have been shown to be neuroprotective, but they failed to reverse chronic oxidative stress produced by lindane. Further studies are required to demonstrate interaction of NS with lindane in oxidative stress.


Keywords


Epilepsy, Neurosteroids, Lindane, PTZ

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References


Wauchope RD, Buttler TM, Hornsky AG, Augutijn-Beckers PW, Burt JP. The SCS/ARS/CES pesticide properties database for environmental decision making. Rev Environ Contam Toxicol. 1992;123:1-155. [DOI via Crossref]

Ecobichon DG. Toxic effects of pesticides. In: Kalaassen CD, editor. Casarett and Doull's Toxicology. New York: McGraw-Hill; 1996: 643-89.

Bagchi M, Stohs SJ. In vitro induction of reactive oxygen species by 2,3,7,8-tetrachlorodibenzo-p-dioxin, endrin and lindane in rat peritoneal macrophages and hepatic mitochondria and microsomes. Free Radic Biol Med. 1993;14(1):11-8. [DOI via Crossref]

Sharma P, Singh R. Protective role of curcumin on lindane induced Reproductive toxicity in male wistar rats. Bull Environ Contam Toxicol. 2010;84:378-84. [DOI via Crossref]

Bano M, Bhatt DK. Neuroprotective role of a novel combination of certain antioxidants on lindane (γ-HCH) induced toxicity in cerebrum of mice. Res J Agric Biol Sci. 2007;3:664-9.

Bano M, Bhatt DK. Ameliorative effect of a combination of vitamin-E, vitamin-C. α-lipoic acid and stilbene resveratrolon lindane induced toxicity in mice olfactory lobe and cerebrum. Indian J Environ Biol. 2010;48:150-8.

Griffith JA, Woolley DE. "Central" and "peripheral" benzodiazepines and kinetics of lindane-induced toxicity. Pharmacol Biochem Behav. 1989;32:367-76. [DOI via Crossref]

Sahoo A, Samanata L, Chainy GBN. Mediation of oxidative stress in HCH- induced neurotoxicity in rat. Arch Environ Contam Toxicol. 2000;39:7-12. [DOI via Crossref]

Vidala LA, Barross BM, Junqueira VBC. Lindane induced liver oxidative stress. Free Radic Biol Med. 1990;91:69-79.

Paul SM, Purdy RH. Neuroactive steroids. FASEB J. 1992;6(6):2311-22.

Majewska MD. Neurosteroids: endogenous bimodal modulators of the GABAA receptor. Mechanism of action and physiological significance. Prog Neurobiol. 1992;38:379-95. [DOI via Crossref]

Compagnone NA, Mellon SH. Neurosteroids: Biosynthesis and function of these novel neuromodulators. Front Neuroendocrinol. 2000;21:1-56. [DOI via Crossref]

Gavish M, Idit T, Bachmani I, Shoukrun R, Katz Y, Vennnman L, et al. Enigma of the peripheral benzodiazepine receptor. Pharmacol Rev. 1999;51:629-50.

Getova D, Roestl WF, Bowery NG. Effects of GABAB receptors antagonism on the development of PTZ induced kindling in mice. Brain Res. 1998;809:182-8. [DOI via Crossref]

Ohkawa H, Ohish N, Yagi K. Assay for lipid peroxidation in animals by thiobarbituric acid. Anal Biochem. 1979;95:351-8. [DOI via Crossref]

Ellman GC. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959;82:70-7. [DOI via Crossref]

Banerjee BD, Seth V, Ahmmed RS. Pesticide induced oxidative stress. Perspect Trends. 2001;16:1-40.

Reddy DS. Neurosteroids: Endogenous role in the human brain and therapeutic potentials. Prog Brain Res. 2010;186:113-37. [DOI via Crossref]

Akk G, Covey DF, Evers AS, Steinbach JH, Zorumski CF, Mennerick S. The influence of the membrane on neurosteroid actions at GABA-A receptors. Psychoneuroendocrinology. 2009;34:59-66. [DOI via Crossref]

Morrow AL. Recent developments in the significance and therapeutic relevance of neuroactive steroids--Introduction to the special issue. Pharmacol Ther. 2007;116:1-6. [DOI via Crossref]

Sahaya K, Mahajan P, Mediratta PK, Ahmed RS, Sharma KK. Reversal of lindane-induced impairment of step-down passive avoidance and oxidative stress by neurosteroids in rats. Toxicology. 2007;24:116-2. [DOI via Crossref]

Rauca C, Zerbe R, Jantze H. Formation of free hydroxyl radicals after pentylenetetrazol-induced seizure and kindling. Brain Res. 1999;20:347-51. [DOI via Crossref]

Attia AM, EL-Banna SG, Nomeir FR, Abd EL-Basser MI. Lindane induced biochemical perturbation in rat serum and attenuation by Omega -3 and Nigella sativa seed oil. Indian J Biochem Biophys. 2011;48(3):184-90.

Sharma P, Singh R. Dichlorvos and lindane induced oxidative stress in rat brain: Protective effects of ginger. Pharmacognosy Res. 2012;4:27-32. [DOI via Crossref]

Bucolo C, Drago F, Lin LR, Reddy VN. Neuroactive steroids protect retinal pigment epithelium against oxidative stress. Neuroreport. 2005;16:1203-7. [DOI via Crossref]