Rutin-Functionalized Selenium Nanoparticles Attenuate Cisplatin-Induced Cardiohepatic Injury in Rats: Modulation of ER Stress-Related Gene Expression and Mitochondrial Apoptotic Markers

Figure 1. Physicochemical characterization of rutin-mediated selenium nanoparticles (RUT-SeNPs). (A) Dynamic light scattering (DLS); (B) Zeta potential distribution.

Figure 2. Transmission electron micrograph of rutin-mediated selenium nanoparticles (RUT-SeNPs) (A) Original image; (B) Quantitative analysis of 65 counted NPs. Scale bar = 100 nm.

Figure 3. X-ray diffraction (XRD) pattern of rutin-mediated selenium nanoparticles (RUT-SeNPs).

Figure 4. UV–visible spectra of rutin (RUT) and rutin-mediated selenium nanoparticles (RUT-SeNPs).

Figure 5. Effects of rutin-mediated selenium nanoparticles (RUT-SeNPs), rutin, and sodium selenite on cisplatin-induced alterations in hepatic function biomarkers. (A) Serum alanine aminotransferase (ALT) (B) aspartate aminotransferase (AST), (C) albumin (ALB), and (D) total bilirubin levels were assessed in control (CON), cisplatin-treated (CIS), and cisplatin-treated rats receiving rutin, selenium, or RUT-SeNPs. Data are expressed as mean ± standard error (n = 7). Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test. ** p < 0.01, *** p < 0.001, and **** p < 0.0001.

Figure 6. Effects of rutin-mediated selenium nanoparticles (RUT-SeNPs), rutin, and sodium selenite on cisplatin-induced alterations in serum cardiac injury biomarkers. (A) Serum creatine kinase-MB (CK-MB), (B) cardiac troponin T (cTnT), (C) heart-type fatty acid binding protein (FABP3), (D) myosin light chain-3 (MYL3), and (E) atrial natriuretic peptide (ANP) levels were evaluated in control (CON), cisplatin-treated (CIS), and cisplatin-treated rats receiving rutin, selenium, or RUT-SeNPs. Data are represented as mean ± standard error (SEM) (n = 7). Statistical significance was assessed using one-way ANOVA followed by Tukey’s post hoc test. * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001.

Figure 7. Effects of rutin-mediated selenium nanoparticles (RUT-SeNPs), rutin, and sodium selenite on cisplatin-induced alterations in oxidative stress and Keap-1/Nrf2 antioxidant signaling in hepatic and cardiac tissues. (A) Hepatic malondialdehyde (MDA) levels, (B) hepatic Nrf2 mRNA expression, and (C) hepatic Keap-1 mRNA expression, as well as (D) cardiac MDA levels, (E) cardiac Nrf2 mRNA expression, and (F) cardiac Keap-1 mRNA expression, were evaluated in control rats (CON), cisplatin-treated rats (CIS), and cisplatin-treated rats receiving rutin, sodium selenite, or RUT-SeNPs. Data were presented as mean ± standard error (n = 7). Statistical significance was determined using one-way ANOVA followed by Tukey’s post hoc test. * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001.

Figure 8. Effects of rutin-mediated selenium nanoparticles (RUT-SeNPs), rutin, and sodium selenite on cisplatin-induced alterations in antioxidant defense markers in hepatic and cardiac tissues. Hepatic (A) reduced glutathione (GSH), (B) glutathione reductase (GR), (C) glutathione peroxidase (GPx), (D) superoxide dismutase (SOD), and (E) catalase (CAT) levels were assessed, along with corresponding (G) cardiac GSH, (F) GR, (J) GPx, (H) SOD, and (I) CAT activities in control (CON), cisplatin-treated (CIS), and cisplatin-treated rats receiving rutin, selenium, or RUT-SeNPs. Data are presented as mean ± standard error (n = 7). Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test. * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001.

Figure 9. Effects of rutin-mediated selenium nanoparticles (RUT-SeNPs), rutin, and sodium selenite on cisplatin-induced inflammatory markers in hepatic and cardiac tissues. Hepatic (A) tumor necrosis factor-α (TNF-α), (B) nuclear factor kappa B (NF-κB), (C) interleukin-6 (IL-6), and (D) cyclooxygenase-2 (COX-2) levels were evaluated, along with corresponding cardiac (E) TNF-α, (F) NF-κB, (G) IL-6, and (H) COX-2 expression in control (CON), cisplatin-treated (CIS), and cisplatin-treated rats receiving rutin, selenium, or RUT-SeNPs. Data were expressed as mean ± standard error (SEM) (n = 7). Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test. * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001.

Figure 10. Effects of rutin, sodium selenite, and rutin-mediated selenium nanoparticles (RUT-SeNPs) on cisplatin-induced alterations in MAPK, TLR4, and cytochrome c levels in hepatic and cardiac tissues. Hepatic levels of (A) mitogen-activated protein kinase (MAPK), (B) Toll-like receptor 4 (TLR4), and (C) cytochrome c, as well as cardiac levels of (D) MAPK, (E) TLR4, and (F) cytochrome c, were assessed in control rats (CON), cisplatin-treated rats (CIS), and cisplatin-treated rats receiving rutin, sodium selenite, or RUT-SeNPs. Data are presented as mean ± standard error (SEM) (n = 7). Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test. * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001.

Figure 11. Effects of rutin-mediated selenium nanoparticles (RUT-SeNPs), rutin, and sodium selenite on cisplatin-induced modulation of apoptotic gene expression in hepatic and cardiac tissues. Hepatic (A) Bax mRNA expression and (B) BCL-2 mRNA expression, as well as cardiac (C) Bax and (D) BCL-2 transcript levels, were evaluated in control (CON), cisplatin-treated (CIS), and cisplatin-treated rats receiving rutin, selenium, or RUT-SeNPs. Gene expression levels were normalized to β-actin and expressed as fold change relative to the control group. Data are presented as mean ± standard error (SEM) (n = 7). Statistical significance was determined using one-way ANOVA followed by Tukey’s post hoc test. * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001.

Figure 12. Effects of rutin, sodium selenite, and rutin-mediated selenium nanoparticles on cisplatin-induced changes in ER stress-related gene expression in hepatic and cardiac tissues. Hepatic mRNA expression levels of (A) protein kinase RNA-like endoplasmic reticulum kinase (PERK), (B) activating transcription factor 4 (ATF4), (C) activating transcription factor 6 (ATF6), and (D) C/EBP homologous protein (CHOP), as well as cardiac mRNA expression levels of (E) PERK, (F) ATF4, (G) ATF6, and (H) CHOP, were evaluated in control rats (CON), cisplatin-treated rats (CIS), and cisplatin-treated rats receiving rutin, sodium selenite, or RUT-SeNPs. Data presented as mean ± standard error (SEM) (n = 7). Statistical significance was determined using one-way ANOVA followed by Tukey’s post hoc test. * p < 0.05, ** p < 0.01, and **** p < 0.0001.