Abstract
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
Highlights
Liver has many metabolic, storing, and secretory functions
The results showed that 1 g of M contains 419 ± 1.04 μg total phenolics as gallic acid equivalent and 6.8 ± 0.05 μg total flavonoids as quercetin equivalent
The results revealed that M contains different concentrations from potassium, calcium, magnesium, sodium, iron, copper, zinc, and manganese (Table 2)
Summary
Liver has many metabolic, storing, and secretory functions. It secretes bile; forms blood clotting factors; metabolizes carbohydrates, proteins, and fats; stores vitamins, glycogen, and other substances; cleans blood from wastes and toxic matter; and removes old red blood cells (Koolman and Röhm 2005; Rodes et al 2008). 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 CCl4 and T (Shaban et al 2021b, 2022). Cellular antioxidant defense system consists of enzymatic and non-enzymatic factors that maintain cellular redox homoeostasis. Enzymatic factors include superoxide dismutase (SOD), glutathione reductase (GSR), glutathione-S-transferase (GST), and glutathione peroxidase (GPx), while non-enzymatic involving reduced glutathione (GSH), carotenoids, polyphenols, and vitamins (Shaban et al 2013, 2014, 2016a, b). The OS performs in direct or indirect ROS-mediated damage of proteins, nucleic acids, and lipids, and has been implicated in diabetes, atherosclerosis, neurodegeneration, and carcinogenesis (Ray et al 2012)
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