Dendropanax morbifera Léveille extract facilitates cadmium excretion and prevents oxidative damage in the hippocampus by increasing antioxidant levels in cadmium-exposed rats

Abstract

Background: Dendropanax morbifera Léveille is used in herbal medicine as a cancer treatment. In this study, we investigated the effects of Dendropanax morbifera stem extract (DMS) on cadmium (Cd) excretion from the blood and kidney and brain tissues of rats exposed to cadmium, as well as the effects of DMS on oxidative stress and antioxidant levels in the hippocampus after Cd exposure.

Methods: Seven-week-old Sprague-Dawley rats were exposed to 2 mg/kg of cadmium by intragastric gavage and were orally administered 100 mg/kg of DMS for 4 weeks. Animals were sacrificed and Cd determination was performed using inductively coupled plasma mass spectrometry. In addition, the effects of Cd and/or DMS on oxidative stress were assayed by measuring reactive oxygen species production, protein carbonyl modification, lipid peroxidation levels, and antioxidant levels in hippocampal homogenates.

Results: Exposure to Cd significantly increased Cd content in the blood, kidneys, and hippocampi. DMS treatment significantly reduced Cd content in the blood and kidneys, but not in the hippocampi. Exposure to Cd significantly increased reactive oxygen species production, protein carbonyl modification, lipid peroxidation, total sulfhydryl content, reduced glutathione content, and glutathione reductase activity. In contrast, Cu, Zn-superoxide dismutase (SOD1), catalase (CAT), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) activity in the hippocampus were significantly decreased after exposure to Cd, and administration of DMS significantly inhibited these Cd-induced changes.

Conclusion: These results indicate that DMS facilitates cadmium excretion from the kidneys, reduces cadmium-induced oxidative stress in the hippocampus, and modulates SOD1, CAT, GPx, and glutathione-S-transferase activities.

Figure 1

Levels of intracellular reactive oxygen species production as determined by 2′,7′-dichlorofluorescein (DCF) levels (A), protein carbonyl levels (B), and malondialdehyde (MDA) levels (C) in the hippocampi of control, DMS-, Cd-, and Cd-DMS-treated rats. * Indicates a significant difference between the control and Cd groups (P <0.05); ^# indicates a significant difference between the Cd and Cd/DMS groups (P <0.05; n = 5-7 per group). DCF, protein carbonyl, and MDA levels are significantly higher in the Cd group and the administration of DMS to Cd-exposed rats leads to a decrease in DCF, protein carbonyl, and MDA levels. The data represent means ± standard error of the mean (SEM).

Figure 2

Cu, Zn-Superoxide dismutase 1 (SOD1), catalase (CAT), and glutathione peroxidase (GPx) activity in the hippocampi of control, DMS-, Cd-, Cd-DMS-treated rats. * Indicates a significant difference between the control and Cd groups (P <0.05); ^# indicates a significant difference between the Cd and Cd/DMS groups (P <0.05; n = 7 per group). Antioxidant enzyme activities are significantly lower in the Cd group and the administration of DMS to Cd-exposed rats ameliorates the reduction of enzyme activities. The effect on GPx activity is greater than that on SOD1 or CAT activities. The data represent means ± standard error of the mean (SEM).

Figure 3

Total sulfhydryl groups (TSH), reduced glutathione (GSH), glutathione reductase (GR), and glutathione- S -transferase (GST) in the hippocampi of control, DMS-, Cd-, Cd/DMS-treated rats. * Indicates a significant difference between the control and Cd groups (P <0.05); ^# indicates a significant difference between the Cd and Cd/DMS groups (P <0.05; n = 5 per group). GR activity, TSH levels, and GSH levels are significantly increased after exposure to Cd, while GST activity is significantly increased. The administration of DMS to Cd-exposed rats ameliorates or reverses the changes of enzyme activities or levels. The data represent means ± standard error of the mean (SEM).