Al-Olayan Ebtesam M, El-Khadragy Manal F, Alajmi Reem A, Othman Mohamed S, Bauomy Amira A, Ibrahim Shaimaa R, Abdel Moneim Ahmed E
Department of Zoology, Faculty of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Department of Zoology and Entomology, Faculty of Science, University of Helwan, Cairo, Egypt.
BMC Complement Altern Med. 2016 Nov 8;16(1):434. doi: 10.1186/s12906-016-1389-1.
Schistosomiasis is a prevalent parasitic disease found predominantly in tropical and sub-tropical areas of the developing world, with the second highest socioeconomic and public health burden despite strenuous control efforts. In the present study, we aimed to investigate the ameliorative effects of Ceratonia siliqua pod extract (CPE) on liver fibrosis and oxidative stress in mice infected with Schistosoma mansoni.
The schistosomal hepatopathologic mouse model was established by tail immersion with schistosomal cercaria. The extract was given daily for 10 days beginning 42 days post-infection. Liver samples were obtained from mice sacrificed 9 weeks after infection. Liver histopathological changes were observed with hematoxylin-eosin and Masson trichrome staining.
Typical schistosomal hepatopathologic changes were induced in the untreated mice. However, the oral administration of CPE was effective in reducing worm number and the egg load in the liver. This treatment also decreased granuloma size and collagen deposition by inhibiting tissue inhibitor of metalloproteinases-2 (TIMP-2) expression. Schistosomal infection induced oxidative stress by increasing lipid peroxidation (LPO) and nitrite/nitrate (nitric oxide; NO) production along with concomitant decreases in glutathione (GSH) and various antioxidant enzymes, including superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. However, treatment of mice with CPE at 300 or 600 mg/kg inhibited LPO and NO production, increased GSH content, and restored the activities of the antioxidant enzymes compared with untreated infected mice. Furthermore, treatment with CPE inhibited apoptosis, as indicated by the reduced Bax expression in hepatic tissue.
These data indicated that extracts from Ceratonia siliqua pods may play an important role in combating schistosomal hepatopathology and may inhibit granuloma formation and liver fibrosis through down-regulation of TIMP-2 expression.
血吸虫病是一种普遍存在的寄生虫病,主要见于发展中世界的热带和亚热带地区,尽管进行了艰苦的防控努力,但其社会经济和公共卫生负担仍位居第二。在本研究中,我们旨在探讨刺山柑荚提取物(CPE)对曼氏血吸虫感染小鼠肝纤维化和氧化应激的改善作用。
通过尾浸感染血吸虫尾蚴建立血吸虫性肝病小鼠模型。感染后42天开始,每天给予提取物,持续10天。感染9周后处死小鼠,获取肝脏样本。用苏木精-伊红和Masson三色染色观察肝脏组织病理学变化。
未治疗的小鼠出现典型的血吸虫性肝病变化。然而,口服CPE可有效减少虫体数量和肝脏中的虫卵负荷。该治疗还通过抑制金属蛋白酶组织抑制剂-2(TIMP-2)表达,减小了肉芽肿大小并减少了胶原沉积。血吸虫感染通过增加脂质过氧化(LPO)和亚硝酸盐/硝酸盐(一氧化氮;NO)生成,同时降低谷胱甘肽(GSH)和多种抗氧化酶(包括超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽还原酶)的水平,诱导氧化应激。然而,与未治疗的感染小鼠相比,以300或600 mg/kg剂量的CPE治疗小鼠可抑制LPO和NO生成,增加GSH含量,并恢复抗氧化酶的活性。此外,CPE治疗可抑制细胞凋亡,肝组织中Bax表达降低即表明了这一点。
这些数据表明,刺山柑荚提取物可能在对抗血吸虫性肝病中发挥重要作用,并可能通过下调TIMP-2表达抑制肉芽肿形成和肝纤维化。