Acta Vet. Brno 2018, 87: 145-153

Effects of agmatine on chlorpromazine-induced neuronal injury in rat

Bratislav Dejanovic1, Vesna Vukovic-Dejanovic2, Milica Ninkovic3, Irena Lavrnja4, Ivana Stojanovic5, Milos Pavlovic6, Vesna Begovic7, Dusko Mirkovic8, Ivana Stevanovic3

1University of Defence, Military Medical Academy, Faculty of Medicine MMA, Institute of Medical Biochemistry, Belgrade, Serbia
2Insitute for Rehabilitation, Belgrade, Serbia
3University of Defence, Military Medical Academy, Faculty of Medicine MMA, Institute for Medical Research, Belgrade, Serbia
4Institute for Biological Research “Sinisa Stankovic”, Belgrade, Serbia
5University of Nis, Faculty of Medicine, Institute for Biochemistry, Nis, Serbia
6Faculty of Veterinary Medicine, Department of Obstetrics, Belgrade, Serbia
7University of Defence, Military Medical Academy, Faculty of Medicine MMA, Clinic for Infectious and Tropical Disease, Belgrade, Serbia
8Faculty of Pharmacy, Department of Medicinal Biochemistry, Institute for Medical Biochemistry Clinical Centre of Serbia, Belgrade, Serbia

Received February 24, 2017
Accepted May 15, 2018


1. Anderson ME 1986: The DTNB-GSSG reductase recycling assay for total glutathione (GSH + 1/2GSSG). In: Greenwald RA (Ed.): Tissue glutathione. Boca Raton, CRC Press, pp 317-323
2. Auclair C, Voisin E 1985: Nitroblue tetrazolium reduction. In: Greenwald RA (Ed.): Handbook of Methods for Oxygen Radical Research. CRC Press, Florida, pp 123-132
3. Bastianetto S, Danik M, Mennicken F, Williams S, Quirion R 2006: Prototypical antipsychotic drugs protect hippocampal neuronal cultures against cell death induced by growth medium deprivation. BMC Neurosci 7: 28 <>
4. Bishnoi M, Chopra K, Kulkarni SK 2007: Possible anti-oxidant and neuroprotective mechanisms of zolpidem in attenuating typical anti-psychotic-induced orofacial dyskinesia: a biochemical and neurochemical study. Prog Neuropsychopharmacol Biol Psychiatry 31: 1130-1138 <>
5. Bosch-Morell F, Romá J, Marín N, Romero B, Rodriguez-Galietero A, Johnsen-Soriano S, Díaz-Llopis M, Romero FJ 2002: Role of oxygen and nitrogen species in experimental uveitis: anti-inflammatory activity of the synthetic antioxidant ebselen. Free Radic Biol Med 33: 669-75 <>
6. Chai J, Luo L, Hou F, Fan X, Yu J, Ma W, Tang W, Yang X, Zhu J, Kang W, Yan J, Liang H 2016: Agmatine reduces lipopolysaccharide-mediated oxidant response via activating PI3K/Akt pathway and up-regulating Nrf2 and HO-1 expression in macrophages. PLoS One 11: e0163634 <>
7. Cobb CA, Cole MP 2015: Oxidative and nitrative stress in neurodegeneration. Neurobiol Dis 84: 4-21 <>
8. Dejanovic B, Ninkovic M, Stojanovic I, Lavrnja I, Radicevic T, Stevanovic I 2015: Agmatine prevents acute chlorpromazine-induced neurotoxicity in rats. Arh farm 65: 287-303
9. Dejanovic B, Stevanovic I, Ninkovic M, Stojanovic I, Lavrnja I, Radicevic T, Pavlovic M 2016: Agmatine protection against chlorpromazine-induced forebrain cortex injury in rats. J Vet Sci 17: 53-61 <>
10. Djukic M, Jovanovic MD, Ninkovic M, Stevanovic I, Curcic M, Topic A, Vujanovic D, Djurdjevic D 2012: Intrastriatal pre-treatment with L-NAME protects rats from diquat neurotoxicity. Ann Agric Environ Med 19: 666-672
11. Dringen R 2005: Oxidative and antioxidative potential of brain microglial cells. Antioxid Redox Signal 7: 1223-1233 <>
12. Freifelder D 1976: Physical Biochemistry. Application to Biochemistry and Molecular Biology. Freeman WH and Co, San Francisco
13. Gergel D, Cederbaum AI 1996: Inhibition of the catalytic activity of alcohol dehydrogenase by nitric oxide is associated with S nitrosylation and the release of zinc. Biochemistry 35: 16186-16194 <>
14. Girotti M, Khan N, Lellan B 1991: Early measurement of systemic lipid peroxidation products in the plasma of major blunt trauma patients. J Trauma 31: 32-35 <>
15. Góth L 1991: A simple method for determination of serum catalase activity and revision of reference range. Clin Chim Acta 196: 143-151 <>
16. Gurd JW, Jones LR, Mahler HR, Moore WJ 1974: Isolation and partial characterization of rat brain synaptic membrane. J Neurochem 22: 281-290 <>
17. Harry GJ, Schmitt TJ, Gong Z, Brown H, Zawia N, Evans HL 1996: Lead-induced alterations of glial fibrillary acidic protein (GFAP) in the developing rat brain. Toxicol Appl Pharmacol 139: 84-93 <>
18. Hu J, Kulkarni AP 2000: Metabolic fate of chemical mixtures. I. “Shuttle Oxidant” effect of lipoxygenase-generated radical of chlorpromazine and related phenothiazines on the oxidation of benzidine and other xenobiotics. Teratog Carcinog Mutagen 20: 195-208 <<195::AID-TCM2>3.0.CO;2-2>
19. Jorgacevic B, Mladenovic D, Ninkovic M, Prokic V, Stankovic M, Aleksic V, Cerovic I, Vukicevic RJ, Vucevic D, Stankovic M, Radosavljevic T 2013: Dynamics of oxidative/nitrosative stress in mice with methionine-choline-deficient diet-induced nonalcoholic fatty liver disease. Hum Exp Toxicol 33: 701-709 <>
20. Juránek I, Bezek S 2005: Controversy of free radical hypothesis: reactive oxygen species-cause or consequence of tissue injury? Gen Physiol Biophys 24: 263-278
21. Li T, Zhou Q, Zhang N, Luo Y 2008: Toxic effects of chlorpromazine on Carassius auratus and its oxidative stress. J Environ Sci Health B 43: 638-643 <>
22. Lopert P, Patel M 2014: Brain mitochondria from DJ-1 knockout mice show increased respiration-dependent hydrogen peroxide consumption. Redox Biol 2: 667-672 <>
23. Lores-Arnaiz S, D’Amico G, Czerniczyniec A, Bustamante J, Boveris A 2004: Brain mitochondrial nitric oxide synthase: in vitro and in vivo inhibition by chlorpromazine. Arch Biochem Biophys 430: 170-177 <>
24. Lowry OH, Rosenbrongh NJ, Farr AL, Randal RJ 1951: Protein measurement with the folin phenol reagent. J Biol Chem 193: 265-275
25. Navarro-Gonzalez JA, Garcia-Benayas C, Arenas J 1998: Semiautomated measurement of nitrate in biological fluids. Clin Chem 44: 679-681
26. Nemmiche S, Chabane-Sari D, Guiraud P 2007: Role of alpha-tocopherol in cadmium-induced oxidative stress in Wistar rat’s blood, liver and brain. Chem Biol Interact 170: 221-230 <>
27. Parikh V, Khan MM, Mahadik SP 2003: Differential effects of antipsychotics on expression of antioxidant enzymes and membrane lipid peroxidation in rat brain. J Psychiatr Res 37: 43-51 <>
28. Piletz JE, Aricioglu F, Cheng JT, Fairbanks CA, Gilad VH, Haenisch B, Halaris A, Hong S, Lee JE, Li J, Liu P, Molderings GJ, Rodrigues AL, Satriano J, Seong GJ, Wilcox G, Wu N, Gilad GM 2013: Agmatine: clinical applications after 100 years in translation. Drug Discov Today 18: 880-893 <>
29. Randox Laboratories 1996: Ltd. Radicales Libres, Crumlin, United Kingdom, pp 1-16
30. Regunathan S, Youngson C, Raasch W, Wang H, Reis DJ 1996: Imidazoline receptors and agmatine in blood vessels: a novel system inhibiting vascular smooth muscle proliferation. J Pharmacol Exp Ther 276: 1272-1282
31. Reis DJ, Yang XC, Milner TA 1998: Agmatine containing axon terminals in rat hippocampus form synapses on pyramidal cells. Neurosci Lett 250: 185-188 <>
32. Rojczyk E, Pałasz A, Wiaderkiewicz R 2015: Effect of short and long-term treatment with antipsychotics on orexigenic/anorexigenic neuropeptides expression in the rat hypothalamus. Neuropeptides 51: 31-42 <>
33. Safhi MM 2016: Neuromodulatory effects of thymoquinone in extenuating oxidative stress in chlorpromazine treated rats. Acta Pol Pharm 73: 529-535
34. Saha KB, Bo L, Zhao S, Xia J, Sampson S, Zaman RU 2016: Chlorpromazine versus atypical antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev 2016; 4: CD010631
35. Sun M, Zigman S 1978: An important spectrophotometric assay for superoxide dismutase based on epinephrine auto-oxidation. Analytical Biochemistry 90: 81-89 <>
front cover
  • ISSN 0001-7213 (printed)
  • ISSN 1801-7576 (electronic)

Current issue

Indexed in DOAJ