Neuroprotective effect of grape seed extract against cadmium toxicity in male albino rats

Abstract

Cadmium toxicity can disturb brain chemistry leading to depression, anxiety, and weakened immunity. Cadmium disturbs the neurotransmitter dopamine, resulting in low energy, lack of motivation, and depression, which are predisposing factors for violence. The purpose of this study was to evaluate the ameliorative effect of grape seed extract (GSE) on the brain of 40 male albino rats after exposure to cadmium chloride (Cd) toxicity. The rats were separated into either the control group, the Cd group, the GSE group, or the GSE and Cd mixture (treated) group. The cerebrum showed evidence of degeneration of some nerve fibers and cells. Fibrosis, vacuolations, and congestion in the blood vessels were demonstrated. Satelletosis was located in the capsular cells. Immunohistochemical expression of Bax was strongly positive in the Cd group and decreased in the treated group. These histopathological changes were decreased in the brain tissue of the treated group, but a few blood vessels still had evidence of congestion. Cadmium administration increased the level of MDA and decreased MAO-A, acetylcholinesterase, and glutathione reductase (GR), while the treatment with GSE affected the alterations in these parameters. In addition, cadmium downregulated the mRNA expression levels of GST and GPx, while GSE treatment normalized the transcript levels. The expression of both dopamine and 5-hydroxytryptamine transporter was downregulated in the rats administered cadmium and the addition of GSE normalized the expression of these aggression associated genes.

Keywords: cadmium chloride; cerebrum; grape seed extract (GSE); protective role; violence.

Figure 1.

Serum changes in MDA and antioxidant levels in male albino rats after chronic administration of cadmium and protection by grape seed extract for 3 months. The values are means ± SE for 10 rats per each treatment. The serum was analyzed using colorimetric kits. *P <0.05 vs. control and #P <0.05 vs. cadmium group.

Figure 2.

RT-PCR analysis of GST and GPx expression in brain tissue after chronic administration of cadmium in male albino rats. The RNA was extracted and reverse transcribed (3 µg) and RT-PCR analysis was carried out for the GST and GPx genes. Densitometric analysis was carried for 10 rats. *P <0.05 vs. control.

Figure 3.

Changes in MAO mRNA expression (a) and serum MAO levels (b) in male albino rats after chronic administration of cadmium and protection by GSE. (a) RT-PCR analysis of MAO expression in brain tissue after chronic administration of cadmium. The RNA was extracted and reverse transcribed (3 µg) and RT-PCR analysis was carried out for the MAO gene. (b) The values are means ± SE for 10 rats per each treatment. The serum was analyzed using colorimetric kits for MAO. *P <0.05 vs. control, $P <0.05 vs. control, and $P <0.05 vs. cadmium.

Figure 4.

Changes in AChE mRNA expression (a) and serum AChE levels (b) in male albino rats after chronic administration of cadmium and protection by GSE. (a) RT-PCR analysis of AChE expression in brain tissue after chronic administration of cadmium. The RNA was extracted and reverse transcribed (3 µg) and RT-PCR analysis was carried out for the MAO gene. (b) The values are means ± SE for 10 rats per each treatment. The serum was analyzed using colorimetric kits for AChE. *P <0.05 vs. control and #P <0.05 vs. cadmium.

Figure 5.

RT-PCR analysis of DD2R and 5-HTT expression in brain tissue after chronic administration of cadmium in male albino rats. The RNA was extracted and reverse transcribed (3 µg) and RT-PCR analysis was carried out for the DD2R and 5-HTT genes.

Figure 6.

Photomicrograph of the male albino rats brain sections showing the gray matter (gm) and white matter (wm) of the brain (a). H&E 10×. (b) Immunohistochemistry detection of Bax expression in the cerebrum (arrows) is shown at 40×.

Figure 7.

Photomicrograph of the male albino rats brain sections showing, congestion of the meningeal blood vessels (arrows) (a), Masson trichrome 40×. (b) Fibrosis and degeneration in the nerve fibers and cells is shown in (f), Masson trichrome at 40×. (c) Vacuolations in the brain tissue (V) are shown, Masson trichrome at 40×. (d) Immunohistochemistry detection of Bax expression of in the cerebrum is shown (arrows), H&E 40×.

Figure 8.

Photomicrograph of male albino rats brain sections showing congestion in the meningeal blood vessels (C) (a), Masson trichrome 40×. (b) The arrangement of the pyramidal cells and fusiform cells of the cerebrum is shown, H&E 40×. (c) Immunohistochemical detection of Bax expression in the cerebrum is shown (arrows), 40×.