Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, 21511, Egypt.
Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt.
BMC Complement Med Ther. 2021 Dec 30;21(1):302. doi: 10.1186/s12906-021-03479-9.
Oxidative stress (OS) and inflammation are the central pathogenic events in liver diseases. In this study, the protective and therapeutic role of Carica Papaya Linn. seeds extract (SE) was evaluated against the hepatotoxicity induced by carbon tetrachloride (CCl) in rats.
The air-dried papaya seeds were powdered and extracted with distilled water. The phytochemical ingredients, minerals, and antioxidant potentials were studied. For determination of the biological role of SE against hepatotoxicity induced by CCl, five groups of adult male Sprague-Dawley rats were prepared (8 rats per each): C: control; SE: rats were administered with SE alone; CCl: rats were injected subcutaneously with CCl; SE-CCl group: rats were administered with SE orally for 2 weeks before and 8 weeks during CCl injection; SE-CCl-SE group: Rats were administered with SE and CCl as mentioned in SE-CCl group with a prolonged administration with SE for 4 weeks after the stopping of CCl injection. Then, the markers of OS [lipid peroxidation (LP) and antioxidant parameters; glutathione (GSH), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione peroxidase (GPx)], inflammation [nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α, interleukin (IL)-6], fibrosis [transforming growth factor (TGF)-β], apoptosis [tumor suppressor gene (p53)], liver and kidney functions beside liver histopathology were determined.
The phytochemical analyses revealed that SE contains different concentrations of phenolics, flavonoids, terpenoids, and minerals so it has potent antioxidant activities. Therefore, the treatment with SE pre, during, and/or after CCl administration attenuated the OS induced by CCl where the LP was reduced, but the antioxidants (GSH, SOD, GST, and GPx) were increased. Additionally, these treatments reduced the inflammation, fibrosis, and apoptosis induced by CCl, since the levels of NF-κB, TNF-α, IL-6, TGF-β, and p53 were declined. Accordingly, liver and kidney functions were improved. These results were confirmed by the histopathological results.
SE has protective and treatment roles against hepatotoxicity caused by CCl administration through the reduction of OS, inflammation, fibrosis, and apoptosis induced by CCl and its metabolites in the liver tissues. Administration of SE for healthy rats for 12 weeks had no adverse effects. Thus, SE can be utilized in pharmacological tools as anti-hepatotoxicity.
氧化应激（OS）和炎症是肝脏疾病的主要致病事件。在这项研究中，评估了番木瓜籽提取物（SE）对四氯化碳（CCl）诱导的大鼠肝毒性的保护和治疗作用。
将风干的番木瓜籽研磨成粉，用蒸馏水提取。研究了植物化学成分、矿物质和抗氧化能力。为了确定 SE 对 CCl 诱导的肝毒性的生物学作用，制备了五组成年雄性 Sprague-Dawley 大鼠（每组 8 只）：C：对照组；SE：大鼠单独给予 SE；CCl：大鼠皮下注射 CCl；SE-CCl 组：大鼠在 CCl 注射前 2 周和注射期间 8 周给予 SE 口服；SE-CCl-SE 组：大鼠如 SE-CCl 组所述给予 SE 和 CCl，并在停止 CCl 注射后 4 周内延长 SE 给药。然后，测定 OS 的标志物[脂质过氧化（LP）和抗氧化参数；谷胱甘肽（GSH）、超氧化物歧化酶（SOD）、谷胱甘肽-S-转移酶（GST）、谷胱甘肽过氧化物酶（GPx）]、炎症[核因子（NF）-κB、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6]、纤维化[转化生长因子（TGF）-β]、细胞凋亡[肿瘤抑制基因（p53)]，以及肝肾功能，同时还进行了肝组织病理学检查。
植物化学分析表明，SE 含有不同浓度的酚类、类黄酮、萜类和矿物质，因此具有很强的抗氧化活性。因此，在 CCl 给药前、期间和/或之后给予 SE 治疗可减轻 CCl 诱导的 OS，降低 LP，但增加抗氧化剂（GSH、SOD、GST 和 GPx）。此外，这些治疗降低了 CCl 诱导的炎症、纤维化和细胞凋亡，因为 NF-κB、TNF-α、IL-6、TGF-β 和 p53 的水平下降。因此，改善了肝肾功能。这些结果得到了组织病理学结果的证实。
SE 通过减少 CCl 及其在肝组织中的代谢物诱导的 OS、炎症、纤维化和细胞凋亡，对 CCl 给药引起的肝毒性具有保护和治疗作用。健康大鼠给予 SE 12 周无不良反应。因此，SE 可用作抗肝毒性的药理学工具。
