Biochemical and pathophysiological improvements in rats with thioacetamide induced-hepatocellular carcinoma using aspirin plus vitamin C

Abstract

Background Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death, so we should be concerned and look for effective/less-harmful treatments than chemotherapeutics already clinically in application. Aspirin works well ''in conjunction'' with other therapies for HCC since aspirin can boost the sensitivity of anti-cancer activity. Vitamin C also was shown to have antitumor effects. In this study, we examined the anti-HCC activities of synergistic combination (aspirin and vitamin C) vs. doxorubicin on HCC-bearing rats and hepatocellular carcinoma (HepG-2) cells. Methods In vitro, we evaluated IC50 and selectivity index (SI) using HepG-2 and human lung fibroblast (WI-38) cell lines. In vivo, four rat groups were used: Normal, HCC (intraperitoneally (i.p.) administered 200 mg thioacetamide/kg/twice a week), HCC + DOXO (HCC-bearing rats i.p. administered 0.72 mg doxorubicin (DOXO)/rat/once a week), and HCC + Aspirin + Vit. C (i.p. administered vitamin C (Vit. C) 4 g/kg/day after day concomitant with aspirin 60 mg/kg/orally day after day). We evaluated biochemical factors [aminotransferases (ALT and AST), albumin, and bilirubin (TBIL) spectrophotometrically, caspase 8 (CASP8), p53, Bcl2 associated X protein (BAX), caspase 3 (CASP3), alpha-fetoprotein (AFP), cancer antigen 19.9 (CA19.9), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) using ELISA], and liver histopathologically. Results HCC induction was accompanied by significant time-dependent elevations in all measured biochemical parameters except the p53 level significantly declined. Liver tissue architecture organization appeared disturbed with cellular infiltration, trabeculae, fibrosis, and neovascularization. Following drug medication, all biochemical levels significantly reversed toward normal, with fewer signs of carcinogenicity in liver tissues. Compared to doxorubicin, aspirin & vitamin C therapy ameliorations were more appreciated. In vitro, combination therapy (aspirin & vitamin C) exhibited potent cytotoxicity (HepG-2 IC50 of 17.41 ± 1.4 µg/mL) and more excellent safety with a SI of 3.663. Conclusions Based on our results, aspirin plus vitamin C can be considered reliable, accessible, and efficient synergistic anti-HCC medication.

Ferulic acid interventions ameliorate NDEA-CCl4-induced hepatocellular carcinoma via Nrf2 and p53 upregulation and Akt/PKB-NF-κB-TNF-α pathway downregulation in male Wistar rats

“…Studies have shown that constantly elevated serum α-FP concentration correlates with belligerent tissue morphology of HCAR, like vascular invasion and satellitosis [29] , [30] . In this study, the elevated level of serum α-FP that was seen is a corroboration of the NDEA-CCl 4 -induced HCAR in the rats [14] , [31] , [32] . FEAC’s ability to lower the serum level of α-FP following its interventions against the NDEA-CCl 4 -induced HCAR is also pointing to its anticancer effect as documented by Zhai et al [27] in a review article.…”

Synthesis and biological evaluation of titanium dioxide/thiopolyurethane composite: anticancer and antibacterial effects

“…This new nanocomposite demonstrated excellent selectivity to attack tumor cells (MCF-7 and HT-29) compared to normal cells (HSFs) [ 61 ]. El Sadda et al studied vitamin C and aspirin against the HepG-2 cell line; they showed higher selectivity than doxorubicin, which is referred to as standard therapy [ 62 ]. Also, similar to Payolla et al, vanadium-based compounds showed a greater selectivity index and better in vitro results than cisplatin [ 63 ].…”

Rifampicin efficacy against doxorubicin-induced cardiotoxicity in mice

“…Doxorubicin antineoplastic drug’s threat to various organs, particularly the heart, has been a motif for researchers to search for solutions in different ways [ 29 , 30 ]. In the present investigation, doxorubicin-induced cardiac toxicity was confirmed histopathologically; dispersed myofibrils separated by congested blood vessels were observed.…”