A Mechanistic Study of the Physiological and Molecular Alleviation of Carbon Tetrachloride (CCl₄)-Induced Hematotoxicity using Biosynthesized Selenium Nanoparticles in a Rat Model
Keywords:
Selenium Nanoparticles, Green Synthesis, CCl4, Hematotoxicity, Oxidative Stress, Nrf2, TNF-α, RT-qPCR, Wistar RatAbstract
Background: Carbon tetrachloride (CCl₄) is an established hepato- and hematotoxic agent that causes oxidative stress, dysregulates erythropoiesis and induces inflammatory pathways. Selenium nanoparticles (SeNPs) bio-synthesized have displayed strong anti-oxidants and anti-inflammatory properties. Yet, their mechanism of action in reversing CCl₄-induced hematotoxicity has not been adequately investigated.
Objective: To assess the potential of green-synthesized SeNPs to reduce CCl₄-induced hematotoxicity in a Wistar rat model by analyzing specific haematological parameters, oxidative stress, liver enzyme levels, and the expression of Nrf2 and TNF-α.
Methods: Using TEM and UV–Vis spectroscopy, the formation of green tea (Camellia sinensis) leaf extract biosynthesized SeNPs was observed. Eight male Wistar rats (N=32) in each of the four groups (Control, CCl₄ (1 mL/kg i.p. 2 times a week for 30 days), CCl₄ + SeNPs (0.5 mg/kg/day, orally) and SeNPs on their own) were chosen at random. CBC, ALT, and AST were determined using standard biochemical methods. Oxidative stress markers (SOD, GSH, CAT, and MDA) and hepatic mRNA expression levels of Nrf2 and TNF-α were assessed by RT-qPCR.
Results: SeNPs had an average size of 48.3 ± 6.2 nm and were UV-Vis active at 270 nm. CCl₄ caused a drastic reduction in RBC (4.91 × 10⁶/µL), Hb (9.2 g/dL), Hct (28.6%), and PLT (185 × 10³/µL) and increased MDA (12.6 nmol/mL) and ALT (96.7 U/L), AST (112.4 U/L). It also caused Nrf2 downregulation (fold-change: 0.38), and increased TNF-α (fold-change: 4.62; all p < 0.001). SeNPs significantly attenuated these alterations, restoring all impacted haematological parameters to greater than 88% of the Control values. SeNPs also restored the disturbed balance of the antioxidant markers, decreased the liver enzymes by more than 55%, and improved the Nrf2 (0.86) and TNF-α (1.94) levels with statistical significance (p < 0.05) when compared to the CCl₄ group.
Conclusion: The present study showed that biomolecule-assisted SeNPs decrease CCl₄-induced blood toxicity and inflammation due to the activation of the Nrf2/Keap1 pathway. Also, SeNPs suppress TNF-α mediated inflammation offering a safe haematoprotective agent
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