J Vet Sci.  2016 Mar;17(1):53-61. 10.4142/jvs.2016.17.1.53.

Agmatine protection against chlorpromazine-induced forebrain cortex injury in rats

• Dejanovic
• Stevanovic I
• Ninkovic M
• Stojanovic I
• Lavrnja I
• Radicevic
• Pavlovic M

• KMID: 2363335
• DOI: http://doi.org/10.4142/jvs.2016.17.1.53

Abstract

This study was conducted to investigate whether agmatine (AGM) provides protection against oxidative stress induced by treatment with chlorpromazine (CPZ) in Wistar rats. In addition, the role of reactive oxygen species and efficiency of antioxidant protection in the brain homogenates of forebrain cortexes prepared 48 h after treatment were investigated. Chlorpromazine was applied intraperitoneally (i.p.) in single dose of 38.7 mg/kg body weight (BW) The second group was treated with both CPZ and AGM (75 mg/kg BW). The control group was treated with 0.9% saline solution in the same manner. All tested compounds were administered i.p. in a single dose. Rats were sacrificed by decapitation 48 h after treatment Treatment with AGM significantly attenuated the oxidative stress parameters and restored antioxidant capacity in the forebrain cortex. The data indicated that i.p. administered AGM exerted antioxidant action in CPZ-treated animals. Moreover, reactive astrocytes and microglia may contribute to secondary nerve-cell damage and participate in the balance of destructive vs. protective actions involved in the pathogenesis after poisoning.

Keyword

agmatine; antioxidant defense; astrocytes; chlorpromazine; oxidative stress

MeSH Terms

Agmatine/*pharmacology
Animals
Antioxidants/pharmacology
Chlorpromazine/toxicity
Oxidative Stress/*drug effects
Prosencephalon/*drug effects
Rats
Rats, Wistar
Agmatine
Antioxidants
Chlorpromazine

Figure

• 

  Fig. 1 Tiobarbituric acid reactive substances production (TBARS) concentration (A) and O2•− production (B) in rat forebrain cortex. Data are expressed as the means ± SEM. Significant differences between control group (*) and CPZ group (†) were considered (*,†p < 0.05, ††p < 0.01, ***,†††p < 0.001, one way ANOVA, Dunnett's C test).

• 

  Fig. 2 Total glutathione (GSH) content in rat forebrain cortex. Data are expressed as the mean ± SEM. Significant differences between control group (*) and CPZ group (†) were considered (*,†p < 0.05, ***,†††p < 0.001, one way ANOVA, Dunnett's C test).

• 

  Fig. 3 Total superoxide dismutase (SOD) activity (A) and catalage (CAT) activity (B) in rat forebrain cortex. Data are expressed as the mean ± SEM. Significant differences between control group (*) and CPZ group (†) were considered (†p < 0.05, ††p < 0.01, ***,†††p < 0.001, one way ANOVA, Dunnett's C test).

• 

  Fig. 4 Activities of glutathione peroxidase (GPx) (A) and glutathione reductase (GR) (B) in rat forebrain cortex. Data are expressed as the mean ± SEM. Significant differences between control group (*) and CPZ group (†) were considered (*p < 0.05, ††p < 0.01, †††p < 0.001, one way ANOVA, Dunnett's C test).

• 

  Fig. 5 Representative photomicrographs of glial fibrillary acidic protein (GFAP) staining by immunohistochemistry of brain sections in the control group (A), CPZ group (B), CPZ+AGM group (C) and AGM group (D) 48 h after CPZ administration. Five rats were tested for each group. 400× (A–D).

• 

  Fig. 6 Representative photomicrographs of Iba1 staining by immunohistochemistry of brain sections in the control group (A), CPZ group (B), CPZ+AGM group (C) and AGM group (D) 48 h after CPZ administration. Five rats were tested for each group. 400× (A–D).

• 

  Fig. 7 Quantitative immunoblot detection of GFAP protein levels in forebrain cortex isolated from the control, CPZ, CPZ+AGM and AGM group 48 h after treatment. Bars represent the mean GFAP protein abundance (± SEM) from three independent determinations expressed relative to β-actin. Significance is shown in the graph (*p < 0.05 vs. control), which is accompanied by a representative immunoblot.

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