Selenium Nanoparticles Dispersed in Phytochemical Exert Anti-Inflammatory Activity by Modulating Catalase, GPx1, and COX-2 Gene Expression in a Rheumatoid Arthritis Rat Model

Abstract

BACKGROUND Literature shows that serum selenium concentration is low in rheumatoid arthritis (RA) patients. Biochemical properties of nanoparticles (NPs) are depend in its medium dispersed. Biochemical properties could effectively alter the therapeutic potential of NPs. Phytochemicals could serve as suitable medium for dispersion of NPs. P-Coumaric acid (CA) known to have anti-inflammatory activity. MATERIAL AND METHODS In the present experiment, we investigated the anti-inflammatory effect of SeNPs dispersed in 1% CA against Complete Freund's adjuvant induced RA. Celecoxib was used as a reference drug. RESULTS Selenium NPs (SeNPs) size is maintained in 1% CA solution. We observed that supplementation with 500 μg/Kg body weight (b.w.) eNPs significantly restored the levels of thiobarbituric acid reactive substances, COX-2 activity, different antioxidant enzyme activities, and inflammatory cytokines (TNF-α, IL-1β, IL-6, and MCP-1) in RA rats. The mRNA expression of antioxidant enzymes such as MnSOD, Cu/ZnSOD, ECSOD, CAT, and GPx1 was found to be downregulated, whereas COX-2 was upregulated in RA rats; however, the mRNA expression of CAT, GPx1, and COX-2 reverted back to near normal levels in SeNPs-treated animals. CONCLUSIONS The therapeutic potential of SeNPs was confirmed through histological observation of angle joints in different experimental animals. Our results collectively suggest that SeNPs dispersed in CA can be an effective therapeutic agent for inflammatory disorders like acute gouty arthritis.

Figure 1

SeNPs status in different media. (A) SeNPs dispersed in water (immediately after dispersion=0 h). (B) SeNPs dispersed in water (after=24 h). (C) SeNPs dispersed in 0.1% DMSO (after=24 h). (D) SeNPs dispersed in 15 CA (after=24 h). Size determination by DLS analysis. Values are shown as the mean ± standard deviation of 3 independent experiments.

Figure 2

Effect of SeNPs on paw edema and body weight changes in different experimental animals. (A) Representative image of knee joints in different experimental animals. (B) Paw edema (cm³) on different days of various experimental groups. (C) Average body weight changes in different experimental animals. Values are shown as mean ±SEM (n=6). Differences were analyzed by one-way ANOVA and Tukey’s post hoc test. ‘a’ vs. control; ‘b’ vs. RA rats; ‘c’ vs. standard drug treated animals. * p<0.05; ^@ p<0.01 and ^# p<0.001.

Figure 3

Levels of TBARS and GSH in different experimental groups. (A) TBARS and (B) GSH. Values are shown as mean ±SEM (n=6). Differences were analyzed by one-way ANOVA and Tukey’s post hoc test. ‘a’ vs. control; ‘b’ vs. RA rats; ‘c’ vs. standard drug treated animals. * p<0.05; ^@ p<0.01 and ^# p<0.001.

Figure 4

COX-2 activity in different experimental animals. Values are shown as mean ±SEM (n=6). Differences were analyzed by one-way ANOVA and Tukey’s post hoc test. ‘a’ vs. control; ‘b’ vs. RA rats; ‘c’ vs. standard drug treated animals. * p<0.05; ^@ p<0.01 and ^# p<0.001.

Figure 5

Levels of different antioxidant enzyme gene expression levels in control and experimental animals. (A) MnSOD, Cu/ZnSOD, and ECSOD. (B) CAT, GPX1, GPX1-, and COX-2. Values are shown as mean ±SEM (n=6). Differences were analyzed by one-way ANOVA and Tukey’s post hoc test. ‘a’ vs. control; ‘b’ vs. RA rats; ‘c’ vs. standard drug treated animals. * p<0.05; ^@ p<0.01 and ^# p<0.001.

Figure 6

Levels of pro-inflammatory cytokines in control and experimental animals. (A) TNFα, (B) IL1β, (C) IL6, and (D) MCP-1. Values are shown as mean ±SEM (n=6). Differences were analyzed by one-way ANOVA and Tukey’s post hoc test. ‘a’ vs. control; ‘b’ vs. RA rats; ‘c’ vs. standard drug treated animals. * p<0.05; ^@ p<0.01 and ^# p<0.001.

Figure 7

Histological observation of knee joints. (A) Representative images of knee joints of different experimental groups. (B) Histopathological score. Values are mentioned as mean ±SEM (n=6). Differences were analyzed by one-way ANOVA Tukey’s post hoc test. ‘a’ vs. control; ‘b’ vs. RA rats. * p<0.05; ^@ p<0.01 and ^# p<0.001.