Nephroprotective Effects of Selenium Nanoparticles Against Sodium Arsenite-Induced Damages

Abstract

Introduction: The potential effects of selenium nanoparticles (SeNPs) administration on arsenic exposure-mediated nephrotoxicity by alleviating fibrosis, inflammation, oxidative stress-related damage, and apoptosis remains more detailed investigations.

Methods: After the synthesis of selenium nanoparticles (SeNPs) by sodium selenite (Na₂SeO₃) through a versatile and green procedure, the biosafety of SeNPs was assessed by assaying renal functions and inflammation in mice. Subsequently, nephroprotective effects of SeNPs against sodium arsenite (NaAsO₂)-induced damages were confirmed by biochemical, molecular, and histopathological assays, including renal function, histological lesion, fibrosis, inflammation, oxidative stress-related damage, and apoptosis in mice renal tissues and renal tubular duct epithelial cells (HK2 cells).

Results: The excellent biocompatibility and safety of SeNPs prepared in this study were confirmed by the non-significant differences in the renal functions and inflammation levels in mice between the negative control (NC) and 1 mg/kg SeNPs groups (p>0.05). The results of biochemical, molecular, and histopathological assays confirmed that daily administration of 1 mg/kg SeNPs for 4 weeks not only ameliorated renal dysfunctions and injuries caused by NaAsO₂ exposure but also inhibited the fibrosis, inflammation, oxidative stress-related damage, and apoptosis in the renal tissues of NaAsO₂-exposed mice. In addition, altered viability, inflammation, oxidative stress-related damage, and apoptosis in the NaAsO₂-exposed HK2 cells were effectively reversed after 100 μg/mL SeNPs supplementation.

Conclusion: Our findings authentically confirmed the biosafety and nephroprotective effects of SeNPs against NaAsO₂ exposure-induced damages by alleviating inflammation, oxidative stress-related damage, and apoptosis.

Keywords: apoptosis; arsenite; inflammation; nephroprotective; oxidative stress; selenium nanoparticles.

Figure 1

Characterization and biocompatibility of SeNPs. (A) TEM assessment of SeNPs. (B) Particles size distribution of SeNPs. (C) XRD pattern of SeNPs. (D) Plasma BUN level. (E) Plasma CRE level. (F) Plasma AST level. (G) Plasma ALT level. (H) Plasma IL-1β level. (I) Plasma IL-10 level.

Figure 2

Effect of SeNPs interventions on renal dysfunctions caused by in vivo NaAsO₂ exposure. (A) Renal index. (B) Plasma BUN level. (C) Plasma CRE level.

Figure 3

Effect of SeNPs interventions on abnormal renal fibrosis caused by in vivo NaAsO₂ exposure. (A) HE staining. (B) PAS staining. (C) Masson trichrome staining. (D) Alcian blue staining. (E) Resorcinol staining. (F) Van Gieson staining. (G) IHC staining of α-SMA. (H) IHC staining of fibronectin. (I) Relative staining intensity of α-SMA. (J) Relative staining intensity of fibronectin. (K) α-SMA expression. (L) Fibronectin expression.

Figure 4

Effect of SeNPs interventions on increased oxidative stress-related damage caused by in vivo NaAsO₂ exposure. (A) Renal SOD activity. (B) Renal GSH activity. (C) Renal CAT activity. (D) Renal MDA activity. (E) Sod2 expression. (F) Catalase expression. (G) Gpx expression.

Figure 5

Effect of SeNPs interventions on abnormal renal inflammation and altered apoptosis caused by the in vivo NaAsO₂ exposure. (A) Plasma IL-1β levels. (B) Plasma IL-10 levels. (C) IHC staining of IL-1β. (D) Relative staining intensity of IL-1β. (E) IHC staining of IL-10. (F) Relative staining intensity of IL-10. (G) IHC staining of Bax. (H) Relative staining intensity of Bax. (I) IHC staining of Bcl-2. (J) Relative staining intensity of Bcl-2. (K) IL-1β expression. (L) IL-10 expression. (M) Bax expression. (N) Bcl-2 expression.

Figure 6

Effect of SeNPs supplementation on inflammation, oxidative stress-related damage, and apoptosis in NaAsO₂-exposed HK2 cells. (A) Representative MitoTracker staining result. (B) Relative staining intensity of MitoTracker. (C) Representative JC-1 staining result. (D) Relative staining ratio of J-AGG/J-MON. (E) Representative DCFH-DA staining result. (F) Relative staining intensity of DCFH-DA. (G) SOD activity of HK2 cells. (H) GSH activity of HK2 cells. (I) CAT activity of HK2 cells. (J) MDA activity of HK2 cells. (K) IL-1β level of HK2 cells. (L) IL-10 level of HK2 cells. (M) Representative IF staining results of γH2A. (N) Relative staining intensity of γH2A.