Using Green Biosynthesized Lycopene-Coated Selenium Nanoparticles to Rescue Renal Damage in Glycerol-Induced Acute Kidney Injury in Rats

Abstract

Purpose: Selenium nanoparticles (SeNPs) have recently gained much attention in nanomedicine applications owing to their unique biological properties. Biosynthesis of SeNPs using nutraceuticals as lycopene (LYC) maximizes their stability and bioactivities. In this context, this study aimed to elucidate the renoprotective activity of SeNPs coated with LYC (LYC-SeNPs) in the acute kidney injury (AKI) model.

Methods: Rats were divided into six groups: control, AKI (glycerol-treated), AKI+sodium selenite (Na₂SeO₃; 0.5 mg/kg), AKI+LYC (10 mg/kg), AKI+LYC-SeNPs (0.5 mg/kg) and treated for 14 days.

Results: Glycerol treatment evoked significant increases in rhabdomyolysis-related markers (creatine kinase and LDH). Furthermore, relative kidney weight, Kim-1, neutrophil gelatinase-associated lipocalin (NGAL), serum urea, and creatinine in the AKI group were elevated. Glycerol-injected rats displayed declines in reduced glutathione level, and superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities, paralleled with downregulations in Nfe2l2 and Hmox-1 expressions and high renal MDA and NO contents. Glycerol-induced renal inflammation was evident by rises in TNF-α, IL-1β, IL-6, and upregulated Nos2 expression. Also, apoptotic (elevated caspase-3, Bax, and cytochrome-c with lowered Bcl-2) and necroptotic (elevated Pipk3 expression) changes were reported in damaged renal tissue. Co-treatment with Na₂SeO₃, LYC, or LYC-SeNPs restored the biochemical, molecular, and histological alterations in AKI. In comparison with Na₂SeO₃ or LYC treatment, LYC-SeNPs had the best nephroprotective profile.

Conclusion: Our findings authentically revealed that LYC-SeNPs co-administration could be a prospective candidate against AKI-mediated renal damage via antioxidant, anti-inflammatory, anti-apoptotic and anti-necroptotic activities.

Keywords: acute kidney injury; apoptosis; inflammation; lycopene; necroptosis; oxidative stress; selenium nanoparticles.

Figure 1

Characterization of lycopene-coated selenium nanoparticles (LYC-SeNPs). (A) Color of LYC-SeNPs at 24 h. (B) Hydrodynamic diameter of LYC-SeNPs by Zetasizer. (C) Surface charge of LYC-SeNPs by Zeta potential. (D) XRD spectra of LYC-SeNPs. (E) Morphological shape of LYC-SeNPs as observed by TEM. (F) FT-IR spectra of LYC-SeNPs.

Figure 2

The effect of lycopene coated selenium nanoparticles (LYC-SeNPs) on the rhabdomyolysis related parameters in glycerol-induced AKI model in rats. Data are expressed as mean ± SEM, n = 7. The statistical difference between groups was estimated using Duncan’s post-hoc test at P < 0.05. Bars that do not share same letters (superscripts) are significantly different from each other (p < 0.05).

Figure 3

The effect of lycopene coated selenium nanoparticles (LYC-SeNPs) on kidney weight and renal function markers in glycerol-induced acute kidney injury. Data are expressed as mean ± SEM, n = 7. The statistical difference between groups was estimated using Duncan’s post-hoc test at P < 0.05. Bars that do not share same letters (superscripts) are significantly different from each other (p < 0.05).

Figure 4

The effect of lycopene coated selenium nanoparticles (LYC-SeNPs) on non-enzymatic antioxidant parameters [malondialdehyde (MDA), nitric oxide (NO), and glutathione (GSH)] levels in glycerol-induced AKI in rats. Data are expressed as mean ± SEM, n = 7. The statistical difference between groups was estimated using Duncan’s post-hoc test at P < 0.05. Bars that do not share same letters (superscripts) are significantly different from each other (p < 0.05).

Figure 5

The effect of lycopene coated selenium nanoparticles (LYC-SeNPs) on antioxidant enzymatic activities in glycerol-induced acute kidney injury. Data are expressed as mean ± SEM, n = 7. The statistical difference between the control and glycerol injected groups was estimated using Duncan’s post-hoc test at P < 0.05. Bars that do not share same letters (superscripts) are significantly different from each other (p < 0.05).

Figure 6

The effect of lycopene coated selenium nanoparticles (LYC-SeNPs) on mRNA expression of Nfe212 and Hmox-1 in glycerol-induced AKI in rats. Data are expressed as mean ± SEM, n = 7. The obtained results were demonstrated as the mean ± SEM of triplicate experiments and were referenced to Gapdh and represented as a fold change (log2 scale), with respect to mRNA levels in the control group. The statistical difference between groups was estimated using Duncan’s post-hoc test at P < 0.05. Bars that do not share same letters (superscripts) are significantly different from each other (p < 0.05).

Figure 7

The effect of lycopene coated selenium nanoparticles (LYC-SeNPs) on the levels of inflammatory biomarkers (TNF-α, IL-1β and IL-6) and Nos2 mRNA expression in glycerol-induced AKI in rats. For ELISA results, data are expressed as mean ± SEM, n = 7. The statistical difference between the control and glycerol injected groups was estimated using Duncan’s post-hoc test at P < 0.05. Bars that do not share same letters (superscripts) are significantly different from each other (p < 0.05). For qRT-PCR findings, the obtained results were demonstrated as the mean ± SEM of triplicate experiments and were referenced to Gapdh and represented as a fold change (log2 scale), with respect to mRNA levels in the control group.

Figure 8

The effect of lycopene coated selenium nanoparticles (LYC-SeNPs) on the levels of apoptotic and necroptotic related markers in glycerol-induced AKI in rats. For ELISA results, data are expressed as mean ± SEM, n = 7. The statistical difference between groups was estimated using Duncan’s post-hoc test at P < 0.05. Bars that do not share same letters (superscripts) are significantly different from each other (p < 0.05). For qRT-PCR findings, the obtained results were demonstrated as the mean ± SEM of triplicate experiments and were referenced to Gapdh and represented as a fold change (log2 scale), with respect to mRNA levels in the control group.

Figure 9

Histopathological alterations in the renal tissue following glycerol injection and different treatments. (A) Control, (B) AKI, (C) Na₂SeO₃+AKI, (D) LYC+AKI, and (E) LYC-SeNPs+AKI. Hematoxylin and eosin (H&E), scale bar= 50 μm.