Therapeutic effect of dithiophenolato chitosan nanocomposites against carbon tetrachloride-induced hepatotoxicity in rats

Abstract

Our previous study showed that dithiophenolate (DTP) and its chitosan nanoparticles (DTP-CSNPs) have abilities to bind with DNA helixes. So in this study, their lethal doses (LD 50 ) and therapeutic roles against rat liver injuries induced by carbon tetrachloride (CCl 4 ) were evaluated. The study focused on the determination of the markers of oxidative stress (OS) and apoptosis and compare the results with those of cisplatin treatment. The results revealed that LD50 values of DTP and DTP-CSNPs are 2187.5 and 1462.5 mg/kg, respectively. Treatment with DPT and DPT-CSNPs after CCl4 administration reduced liver injuries, induced by CCl4, and improved liver functions and architecture through the reduction of OS and apoptosis. Where the oxidant marker was decreased with elevations of antioxidant markers. Also, there was an elevation in Bcl 2 value, with decreases in caspase-8, Bax, and Bax/Bcl 2 ratio. DPT-CSNPs treatment gave preferable results than that treated with DPT. Moreover, DTP and DPT-CSNPs treatment gave better results than Cisplatine treatment. The administration of healthy rats with low doses of DTP and DTP-CSNPs for 14 days had no effect. Otherwise, the study on HepG2 cell line showed that DTP and DPT-CSNPs inhibited cell growth by arresting cells in the G2/M phase and inducing cell death. In conclusion: DTP and DTP-CSNPs have anti-apoptotic and anti-oxidative stress towards hepatotoxicity induced by CCl4. Moreover, DTP and DTP-CSNPs have anticancer activity against the HepG2 cell line. Generally, DTP-CSNPs are more effective than DTP. So, they can be used in the pharmacological elds, especially DTP-CSNPS.

N-Acetyl cysteine alleviates carbon-tetrachloride induced acute liver injury in rats

“…The destructive action of CCL4 is accredited to bio-alteration of cytochrome P4502E1 (CYP2E1) that produces vastly reactive trichloromethyl (CCL3•) free radicals which reacts with oxygen and gives trichloromethyl peroxyl (CCL3OO•) radicals that can attack the lipids and protein of cell membrane bounded to various organs (Zhao et al, 2022). The current study revealed that CCL4 disrupted the lipid metabolism by increasing TC, TG, LDL-c and vLDL-c and lowering HDL-c and these findings matched with previous work of (Shaban et al, 2022). Hypercholesteremia after CCL4 administration may be attributed to hindering the βoxidation of fatty acids (Mahmoodzadeh et al, 2017) and activation the esterification process of lipid (Mesalam et al, 2021).…”

Protective and therapeutic role of mango pulp and eprosartan drug and their anti-synergistic effects against thioacetamide-induced hepatotoxicity in male rats

“… GSH (glutathione), GSSG (reduced glutathione), GPx (glutathione peroxidase), SOD (superoxide dismutase), GST (glutathione-S-transferase), GSR (glutathione reductase), MDA (malonedialdehyde), TNF-α (tumor necrosis factor-α), and PDGF-BB (platelet-derived growth factor-BB), and TGF-β1 (transforming growth factor-beta1 and the data are being presented as the mean ± SD * CI values determine the type of impact between E and M. the effect can be evaluated as synergism (CI < 1), anti-synergism (CI > 1), or additive (CI = 1) (Zhou et al 2007 ; Habashy et al 2018 ; Shaban et al 2020 , 2021a , 2022 ) …”

“…* CI values determine the type of impact between E and M. the effect can be evaluated as synergism (CI < 1), anti-synergism (CI > 1), or additive (CI = 1) (Zhou et al 2007 ; Habashy et al 2018 ; Shaban et al 2020 , 2021a , 2022 )…”

“…The mechanism of the protective and therapeutic effects of M may be related to the antioxidant activity of its contents, including phenolics and flavonoids and their gradients, carotenoids, vitamins, and some minerals. The antioxidant activities of phenolic and flavonoid compounds may be due to their ability to scavenge the ROS and their capability to up-regulate non-enzymatic and enzymatic antioxidants (López et al 2007;Mehra et al 2013;Abdel-Rahman et al 2015;Shaban et al 2016b;Ulla et al Table 4 The combination index (CI)* values for the mango pulp (M) and eprosartan drug (E) co-administration on major tested parameters GSH (glutathione), GSSG (reduced glutathione), GPx (glutathione peroxidase), SOD (superoxide dismutase), GST (glutathione-S-transferase), GSR (glutathione reductase), MDA (malonedialdehyde), TNFα (tumor necrosis factor-α), and PDGF-BB (platelet-derived growth factor-BB), and TGF-β1 (transforming growth factor-beta1 and the data are being presented as the mean ± SD * CI values determine the type of impact between E and M. the effect can be evaluated as synergism (CI < 1), anti-synergism (CI > 1), or additive (CI = 1) (Zhou et al 2007;Habashy et al 2018;Shaban et al 2020Shaban et al , 2021aShaban et al , 2022 2017). Additionally, carotenoids, vitamins as A and C, and some minerals as Zn and Cu play important roles as antioxidants.…”

“…So, the liver is an important target of the toxicity of drugs and xenobiotics through generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) leading to the oxidative stress (OS) (Jaeschke et al 2002 ). ROS and RNS in the hepatocytes are produced by some metabolic reactions such as in the process of mitochondrial oxidative phosphorylation or they may be produced from catabolism of xenobiotic compounds such as CCl 4 and T (Shaban et al 2021b , 2022 ). Cellular antioxidant defense system consists of enzymatic and non-enzymatic factors that maintain cellular redox homoeostasis.…”