Protective effects of resveratrol on the expression of catalase, glutathione peroxidase, and superoxide dismutase genes in the ovary and their activity in the serum of rats exposed to lead acetate: An experimental study

Abstract

Background: Lead (Pb) could be toxic to the female reproductive system, and resveratrol (Res) may overcome this toxicity.

Objective: To investigate the Res impact on the catalase (Cat), glutathione peroxidase (Gpx), and superoxide dismutase (Sod) gene expression in the ovary and on the Cat and Gpx enzyme activity in the serum of rats exposed to lead acetate.

Materials and methods: In this experimental study, 33 female Wistar rats (8-10 wk, 180-200 gr) were divided into 6 groups: a control group (normal saline), a Res group (40 mg/kg), and a Pb group (lead acetate 30 mg/kg). 3 additional groups received lead acetate (30 mg/kg) with Res at 20, 40, and 80 mg/kg for 21 days. Gene expression of Cat, Gpx, and Sod was measured via qPCR, and serum Cat and Gpx activity was assessed using standard methods. Bioinformatics tools were used to evaluate Res effects on gene and protein function.

Results: Lead acetate significantly downregulates Cat, Gpx, and Sod gene expression, but Res significantly upregulates gene expression, especially at doses of 40 mg/kg for Cat, 20 mg/kg and 40 mg/kg for Gpx, and 80 mg/kg for Sod. Cat and Gpx enzyme activity increased and decreased in the lead acetate group, respectively. However, Res in all doses decreased only the Cat enzyme activity. Bioinformatics analysis indicates that Res can interact with the promoter regions and cavities of all 3 enzymes.

Conclusion: Pb can dysregulate the expression and activity of the studied enzymes. However, the impact of Res is influenced by the dose, with 40 mg/kg frequently being the most effective.

Keywords: In silico; Lead acetate; Ovary; Oxidative stress; Rat.; Resveratrol.

Figure 1

Flowchart of study. The stages of the experiment from grouping to treatment and related experiments are summarized in the figure. Ctr: Control, Res: Resveratrol, Pb: Lead acetate, I.P.: Intraperitoneal injection, Cat: Catalase, Gpx: Glutathione peroxidase, Sod: Superoxide dismutase.

Figure 2

Biochemical results. A) Mean $\pm$ SEM of Cat activity in different groups. B) Mean $\pm$ SEM of Gpx activity in different groups. Dissimilar letters indicate significant differences between these groups (p $<$ 0.05). Cat: Catalase, Gpx: Glutathione peroxidase, Pb: Lead.

Figure 3

Relative expression of Cat, Gpx, and Sod genes in different groups. Changes in the expression of A) Cat, B) Gpx, and C) Sod genes due to the administration of Pb and different doses of Res. Pb + R (L): Pb + Res (20 mg/kg), Pb + R (M): Pb + Res (40 mg/kg), Pb + R (H): Pb + Res (80 mg/kg). Res: Resveratrol, Pb: Lead, L: Low dose, M: Medium dose, H: High dose.

Figure 4

Docking results for Cat enzyme. The ligand map shows the interaction of 6 residues A) The proximity of the studied pose to the amino acid cysteine is shown in yellow. B) Steric, C) Hydrogen acceptor, D) Hydrogen donor, E) Electrostatic, and F) Regions are demonstrated by different colors.

Figure 5

A) Docking results for interaction of Res with Gpx enzyme. This interaction could happen near the cysteine residues that are shown in yellow. B) The Res has some interactions such as van der Waals, hydrogen bonds, and covalent bonds with Gpx enzyme.

Figure 6

A) Docking results for interaction of Res with Sod enzyme. This position of Res is in a surface cavity of the molecule. B) The Res has some interactions such as van der Waals, hydrogen bonds, Pi-Cation, Pi-Sigma, Pi-Sulfur, and Pi-Alkyl with Sod enzyme.