4.7 Article

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

期刊

ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
卷 29, 期 34, 页码 51427-51441

出版社

SPRINGER HEIDELBERG
DOI: 10.1007/s11356-022-19383-9

关键词

Mango pulp; Phenolic and flavonoid compounds; Eprosartan; Hypertension; Thioacetamide; Rat hepatotoxicity; Oxidative stress; Hepatic inflammation; Liver fibrosis

资金

  1. Science, Technology & Innovation Funding Authority (STDF)
  2. Egyptian Knowledge Bank (EKB)

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The study evaluated the protective and therapeutic effects of mango pulp (M), eprosartan drug (E), and their combination (EM) against hepatotoxicity induced by thioacetamide (T). The results showed that all treatments significantly reduced T-induced hepatotoxicity by reducing oxidative stress, inflammation, and fibrosis markers. The combined treatment with M and E was less effective than treatment with M or E alone, indicating an anti-synergistic effect between them. Additionally, prophylactic treatment with M demonstrated a better effect in preventing T-induced hepatotoxicity compared to treatment with M after T injection.
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-alpha (TNF-alpha) and platelet-derived growth factor-BB (PDGF-BB) levels and gene expression of transforming growth factor-beta1(TGF-beta(1))], and liver functions and microscopic examination were evaluated. The present results revealed that M contains 419 +/- 1.04 mu g total phenolics as gallic acid equivalent and 6.8 +/- 0.05 mu g 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 mu g 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-alpha and PDGF-BB levels were reduced, and the gene expression of TGF-beta 1 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.

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