Agmatine reduces chlorpromazine prooxidant effects in rat hippocampus and striatum

Authors

  • Bratislav Dejanović Military Medical Academy, Institute of Medical Biochemistry, 11000 Belgrade, Serbia
  • Vesna Begović-Kuprešanin Clinic for Infectious and Tropic Diseases, Military Medical Academy, Belgrade, Serbia
  • Ivana Stevanović Medical Faculty of Military Medical Academy, University of Defense, Institute of Medical Research, Military Medical Academy, 11000 Belgrade, Serbia
  • Irena Lavrnja Institute for Biological Research “Sinisa Stanković” – National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia http://orcid.org/0000-0002-0607-5594
  • Branka Šošić-Jurjević Institute for Biological Research “Sinisa Stanković” – National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia https://orcid.org/0000-0001-6378-1930
  • Milica Ninković Medical Faculty of Military Medical Academy, University of Defense, Institute of Medical Research, Military Medical Academy, 11000 Belgrade, Serbia
  • Svetlana Trifunović Institute for Biological Research “Sinisa Stanković” – National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia https://orcid.org/0000-0002-9141-5732

DOI:

https://doi.org/10.2298/ABS210429028D

Keywords:

chlorpromazine, agmatine, oxidative stress, hippocampus, striatum

Abstract

Paper description:

  • Administration of the antidepressant drug chlorpromazine is linked to increased oxidative stress in the hippocampus and striatum. Agmatine is an adjunct to chlorpromazine therapy used to neutralize its side effects.
  • The ability of agmatine to diminish chlorpromazine prooxidant effects was examined in male rats. Antioxidant enzyme activities were measured in the hippocampus and striatum.
  • Combined chlorpromazine/agmatine treatment decreased the pro-oxidative effects of chlorpromazine.
  • These results validate the coadministration of chlorpromazine and agmatine as a treatment strategy.

Abstract: The use of the antidepressant drug chlorpromazine (CPZ) is linked to the occurrence of oxidative stress in some brain structures. Thus, overcoming the side effects of CPZ is of great importance. Because agmatine (AGM) can act as a free radical scavenger, it is an interesting compound as an adjunct to CPZ therapy. The aim of our study was to investigate the enzymatic parameters of oxidative stress in the hippocampus and striatum of rats after CPZ treatment, and the potential protective effects of AGM. Rats were injected as follows with (i) 1 mL/kg b.w. saline; (ii) a single intraperitoneal (i.p.) dose of CPZ (38.7 mg/kg); (iii) CPZ (38.7 mg/kg) and AGM (75 mg/kg); (iv) AGM (75 mg/kg). CPZ induced an increase in superoxide anion radical (O2•-) concentration, while the activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR), were lowered in both the hippocampus and striatum. Cotreatment with CPZ and AGM protected the examined brain structures by reversing the antioxidant enzyme activities to the control values. Following CPZ treatment, the effects were more pronounced for SOD and GPx in the hippocampus, and for SOD, CAT and GPx in the striatum. The full effect of restored superoxide production was achieved in the striatum, which points to the role of CAT. The obtained results suggest that CPZ in combination with AGM may be considered as a new treatment strategy.

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Published

2021-10-12

How to Cite

1.
Dejanović B, Begović-Kuprešanin V, Stevanović I, Lavrnja I, Šošić-Jurjević B, Ninković M, Trifunović S. Agmatine reduces chlorpromazine prooxidant effects in rat hippocampus and striatum. Arch Biol Sci [Internet]. 2021Oct.12 [cited 2024Apr.20];73(3):353-9. Available from: https://serbiosoc.org.rs/arch/index.php/abs/article/view/6557

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Vol. 73 No. 3 (2021)

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