The present study was done to evaluate the protective and therapeutic role of mango pulp (M), eprosartan drug (E), and their co-administration (EM) against hepatotoxicity induced by thioacetamide (T). Seven groups of rats were prepared as follows: the control (C) group (normal rats), T group (the rats were injected with T), T-M group (the rats were injected with T, and then treated with M), T-E group (the rats were injected with T, and then treated with E), T-EM group (the rats were injected with T, and then treated with E and M), M-TM-M group (the rats were administered with M before, during, and after T injection), and M group (the healthy rats were administered with M only). Firstly, the characterizations of M were determined. Also, the markers of hepatic oxidative stress [malondialdehyde (MDA) and glutathione (GSH) levels and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GSR)], inflammation and fibrosis [(tumor necrosis factor-α (TNF-α) and platelet-derived growth factor-BB (PDGF-BB) levels and gene expression of transforming growth factor-beta1(TGF-β1)], and liver functions and microscopic examination were evaluated. The present results revealed that M contains 419 ± 1.04 μg total phenolics as gallic acid equivalent and 6.8 ± 0.05 μg total flavonoids as quercetin equivalent. The analysis of phenolics and flavonoids showed the presence of chlorogenic, caffeic, 2,5-dihydroxy benzoic, 3,5-dicaffeoylquinic, 4,5-dicaffeoylquinic, tannic, cinnamic acidS, and catechin, phloridzin, and quercetin with different concentrations. Also, M contains various minerals with different concentrations involving potassium, calcium, magnesium, sodium, iron, copper, zinc, and manganese. The current results showed that the total antioxidant capacity of 1 g of M was 117.2 ± 1.16 as μg ascorbic acid equivalent. Our biochemical studies showed that all treatments significantly reduced T-induced hepatotoxicity and liver injuries, as the oxidative stress and inflammatory and fibrotic markers were diminished where MDA level and the activities of GST, GSSG, and GR were decreased when compared with T group. In contrast, GSH level and the activities of SOD and GPx and GSH/GSSG ratio were increased. In addition, TNF-α and PDGF-BB levels were reduced, and the gene expression of TGF-β1 was down-regulated. Consequently, the liver functions were significantly improved. In conclusion, each E, M, and EM has a therapeutic effect against T-induced hepatotoxicity via the reduction of the OS, inflammation, and fibrosis. Unfortunately, treatment with M and E simultaneously revealed the less effectiveness than the treatment with M or E demonstrates the presence of anti-synergistic effect between them. Additionally, M-TM-M treatment showed a better effect than T-M treatment against T-induced hepatotoxicity revealing the prophylactic role of M. The administration of healthy rats with M for 12 weeks has no side effect. Graphical abstract

This study explained the c-myc and p53 gene expression and polymorphisms in chronic (40), cirrhosis (30) and Hepatocellular Carcinoma, (HCC) (30) patients related to Hepatitis B Virus (HBV) infection and healthy control (50) in Egypt. Where, c-myc (intron 8) and p53 (codon 72) gene expression and polymorphisms were determined using qRT-PCR and PCR-RFLP techniques. The results showed that c-myc gene expression (2 ddct) was significantly increased in chronic (1.38), cirrhosis (1.47) and HCC (5.59) compared to the control group (1.00), while p53 gene expression (2 ddct) was significantly decreased compared to the control group (0.82, 0.65, 0.33 and 1.00, respectively). In HCC group, c-myc genotype (CC) was predominant (90%) more than cirrhosis, chronic and control (73.33, 22.5 and 6%, respectively), GG genotype was predominant in control (70%) more than chronic, cirrhosis and HCC groups (67.5, 6.66 and 6.66%, respectively) and GC genotype was high in control (24%) more than cirrhosis, chronic and HCC groups (20, 10 and 3.33%, respectively). p53 PP (88%) genotype was predominant in control more than chronic, cirrhosis and HCC groups (30, 30 and 6.66%, respectively), AA genotype was predominant in HCC group (73.33%) more than chronic, cirrhosis and control (50, 10 and 4%, respectively) and genotype PA was predominant in cirrhosis (60%) more than chronic, HCC and control (20, 20 and 8%, respectively). These results suggest clearly that both c-myc and p53 gene expression and polymorphisms influence clinical outcome and progression of HBV infection and then considered an accurate genetic biomarker to determine and predict the progression of HBV infection.