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

This study was aimed to study the potentially beneficial effects of agmatine on oxidative/nitrosative stress development in the brain of Wistar rats during subacute chlorpromazine treatment. The animals were divided into control (0.9% saline), chlorpromazine (38.7 mg/kg b.w.), chlorpromazine+agmatine (agmatine 75 mg/kg b.w. immediately after chlorpromazine, 38.7 mg/kg b.w. i.p.) and agmatine (75 mg/kg b.w.) groups. All the tested substances were administered intraperitoneally for 15 consecutive days and the rats were sacrificed by decapitation on day 15. Subacute administration of chlorpromazine resulted in increased lipid peroxidation, nitric oxide concentration and superoxide anion production, while completely damaging the antioxidant defence system in the cerebral cortex, striatum, and hippocampus. However, the combined treatment with chlorpromazine and agmatine significantly attenuated the oxidative/nitrosative stress indices and restored the antioxidant capacity to the control values in all of the examined brain regions. Western blot analysis supported biochemical findings in all groups, but the most notable changes were found in the hippocampus. Our results suggest potentially beneficial effects of agmatine, which may be useful in the modified antioxidant approach in chlorpromazine-therapy.


This work was supported by the Military Medical Academy, Projects No. МФВМА/1/18-20, as well as by the Ministry of Education, Science and Technological Development of the Republic of Serbia, Project No. III41014.


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