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

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

Modulation of Nrf2, CBR1, and TNF-a Expressions and Antioxidant Activity Mediated The Cardioprotective Effects of Zingiber Officinale and Moringa Oleifera Extracts Against Doxorubicin-Induced Toxicity

“…Where, SOD reduces the free radicals by converting superoxide radicals (O 2-) to hydrogen peroxide (H2O2) and prevents the formation of hydroxyl radicals through Fenton's reaction [45]. Also, the inhibition of SOD activity may be related to the oxidation of its cysteine residues, which are important in the enzyme's activity [9]. Whereas, the elevation of CAT activity after DOX injection could be a response to the elevation of the free radical generation, especially H2O2 [46].…”

“…Usage of the chemicals that were developed to protect the heart is frequently associated with unwanted side effects, such as weight gain, hypertension, gastric ulcer, and insulin resistance [8]. On the other hand, consumption of vegetables and fruits has been associated with abundant health benefits, as a result of their high nutritious content and therapeutic abilities [9]. For instance; Zingiber officinale (Ginger) has an elongated history in herbal medicine to treat a diversity of disorders including NO: 74104) obtained from Qiagen GmbH, Germany.…”