## 4 Discussion
They activate the Kupffer cells and macrophages that further elicit inflammatory mediators causing fibrosis. The heightened release of free radicals is the first step in a chain of events leading to lipid peroxidation of membraned cell organelles, resulting in apoptosis and necrosis [6]. The elevation in cytokine concentrations and oxidative stress might be the possible chemically-induced liver apoptosis mechanisms [7]. In addition, ROS-mediated lipid peroxidation is the main reason behind the pathogenesis of various liver toxicity and liver fibrosis followed by histological distortion and DNA damage in the target tissues in the experimental animals [8]. CCI4 causes ROS-mediated biotransformation leading to moderate-to-severe toxicity that disturbs cellular redox balance and compromises structural settings in the target tissues [36]. ROS increases lipid peroxidation (MDA levels) and compromises levels of GSH [9] in the target tissues. The histological evaluation of kidney sections further agrees with these conclusions. Results are consistent with the nephrotoxic effect of potassium bromate [37]. Furthermore, CCl4 is converted to highly reactive metabolites that can affect the cellular components (proteins, enzymes, lipids, and nucleic acids) and cellular structures. Moreover, free radicals generated during metabolism and biotransformation of CCl4 cause chromosomal aberrations, DNA-base transversions, DNA adduct formation, and 8-OH dG. Administration of CCl4 causedrotoxicity and DNA fragmentation in hepatic tissues in the male Sprague-Dawley rats [38]. This activity can explain the present study results, in which comet assays show a noticeable increase in DNA tail length in CCl4-treated rats. Hence, CCl4 damages the biological functions of critical biomolecules that disrupt cellular structure and function [39]. The elevated concentration of MDA is a strong index of oxidative stress in CCl4-challenged rats. However, its decreased concentration was observed in the CCl4 administered rats treated with SE-NPs. Thus, the SE-NPs can effectively protect against lipid peroxidation. SE-NPs have shown antioxidant protection in vitro and in vivo studies [29; 31]. All the organisms have effective defense mechanisms that prevent and neutralize damage incurred by free radicals. The NPs restore the activity of GSH and catalase significantly. GSH acts as a non-enzymatic antioxidant that reduces H2O2, hydroperoxides, and xenobiotic toxicity [40]. In contrast, a significant decrease in MDA in hepatic tissues is confirmed after pretreatment with SE-NPs and hence protects against hepatic lipid peroxidation incurred by CCl4. Antioxidant activity and antilipidemic effects of SE-NPs have been reported to modulate blood pressure and alleviate the damage to target organs [41]. GSH is an essential determinant for cell survival or death during disturbed oxidative stress [42]. Inflammatory macrophages and dendritic cells are a physiological defense mechanism for injury and toxicity that are still inadequately addressed by the immune system [43]. Infiltration of inflammatory cells, if prolonged, can exacerbate fibrosis [44]. We previously found that carcinogens trigger all critical pro-inflammatory cytokines (IL-1, 2, 6, and 7) as well as transcription factors (NF-kB and TNF-\(\alpha\)) in target organs [45]. Immune cells then become aggressive, causing extensive inflammation and fibrosis in the liver, as evidenced in histopathological findings. SE-NPs were found to remarkably ameliorate inflammatory infiltration with the immune cells in the hepatic tissues (Figure 6). NF-kB might be downregulated by SE-NPs that induce oxidative stability, although this activity was not addressed in the present study. This amelioration of hepatic seems to be mediated by the ceasing of oxidative stress and suppression of NF-kB, the critical regulator of inflammatory response. Downregulation of NF-kB would exert diminishing production of pro-inflammatory cytokines. Hepatic injury markers are significantly low in the animals treated with any antioxidant treatment.