Cisplatin is an effective chemotherapeutic agent whose clinical use is limited by dose-dependent off-target toxicities, particularly hepatic and cardiac injury. The present study investigated the protective efficacy of rutin-mediated selenium nanoparticles (RUT-SeNPs) against cisplatin-induced hepato-cardiotoxicity in rats and compared their effects against those of free rutin and sodium selenite. RUT-SeNPs were characterized using dynamic light scattering, zeta potential analysis, transmission electron microscopy, X-ray diffraction, and UV–visible spectroscopy. Thirty-five male rats were randomly assigned to five groups: control (CON), cisplatin (CIS), CIS + Rutin, CIS + selenium, and CIS + RUT-SeNPs. Cisplatin administration caused marked hepatic and cardiac injury, as evidenced by altered liver-function indices, elevated cardiac injury biomarkers, oxidative stress, inflammatory activation, endoplasmic reticulum stress, and apoptosis. These effects were associated with increased lipid peroxidation, depletion of endogenous antioxidants, KEAP1 upregulation, Nrf2 suppression, activation of the TLR4/MAPK/NF-κB inflammatory axis, elevated TNF-α, IL-6, and COX-2 levels, and increased mRNA expression of the ER stress-related genes PERK, ATF4, ATF6, and CHOP. Cisplatin also promoted mitochondrial apoptosis, as indicated by increased Bax expression and cytochrome c release together with reduced Bcl-2 levels. Although rutin and sodium selenite partially mitigated these alterations, RUT-SeNPs produced the most pronounced protective effects by restoring redox homeostasis, suppressing inflammatory signaling, reducing the elevated expression of ER stress-related genes, and limiting mitochondrial apoptotic activation. These molecular improvements were accompanied by substantial preservation of the hepatic and cardiac histoarchitecture. Collectively, these results indicate that RUT-SeNPs may represent a promising nanoformulation for reducing cisplatin-induced hepato-cardiac toxicity through coordinated modulation of oxidative stress, inflammation, endoplasmic reticulum stress, and apoptosis.
N. Mahran, Khaled M. Alam-ElDein, Mohamed A. Ali et al.· International Journal of Mol...· 0 citations
Pesticides play a crucial role in agriculture, public health management, and veterinary practice to control pests. However, the persistent use of pesticides poses a significant threat to aquatic ecosystems and non-target organisms, such as fish. The genotoxicity, oxidative stress, and erythrocytic toxicity were assessed in fish exposed to different sublethal concentrations (5, 10, and 15 µg/L) of thiram for 12 days. Blood and other tissues (gills and intestine) were obtained from each fish reared in each group at days 4, 8, and 12 of the experiment. Thin blood film/smear examination indicated significantly (P ≤ 0.05) increased morphological and nuclear changes in erythrocytes, such as the formation of micronuclei, notched nuclei, lobed nuclei, and tear-shaped erythrocytes in fish exposed to higher doses of thiram. The contents of antioxidant enzymes such as catalase (CAT), reduced glutathione (GSH), peroxidase (POD), and superoxide dismutase (SOD) were significantly (P ≤ 0.05) decreased and the oxidative stress biomarkers including reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) were significantly (P ≤ 0.05) increased in gills and intestinal tissues of exposed fish. The results on genotoxicity determined using the comet assay technique revealed significantly (P ≤ 0.05) high levels of genomic instability in terms of DNA damage in isolated cells of the gills and intestine of fish reared in water containing higher concentrations of thiram. At the microscopic level, various sections of the gills of fish treated with higher doses of thiram unveiled moderate to severe histopathological ailments such as degeneration of cartilaginous core, degeneration and disruption of primary and secondary lamellae of gills, necrosis of lamellar epithelial cells, telangiectasia, and curling of secondary lamellae. The findings of this study indicated that extremely low doses of thiram lead to the induction of adverse effects in freshwater fish. Hence, there is a need to develop suitable control measures regarding the use of environmentally friendly chemicals and for the protection of aquatic environments.
