Safarpour Soheila, Safarpour Samaneh, Akbar Moghadamnia Ali, Kazemi Sohrab, Ebrahimpour Anahita, Shirafkan Fatemeh
Student Research Committee, Babol University of Medical Sciences, Babol, Iran.
Department of Pharmacology and Toxicology, School of Medicine, Babol University of Medical Sciences, Babol, Iran.
Saudi Pharm J. 2023 Aug;31(8):101672. doi: 10.1016/j.jsps.2023.06.005. Epub 2023 Jun 16.
5-Fluorouracil (5FUra) is the third most popular chemotherapeutic component employed to treat solid tumors. In the present study, we aimed to appraise the silymarin (SM) and silymarin nanoemulsion (SMN) effect on 5FUra-induced gastrointestinal toxicity in adult male rats. A total of 30 male Wistar rats were divided into 6 groups including the control (Crl) group, and groups treated with SMN (5 mg.kg), SM (5 mg.kg), 5FUra + SMN (5 mg.kg), and 5FUra + SM (5 mg.kg) by IP injection for 14 days. And gastrointestinal toxicity was induced by a single intraperitoneal (IP) injection of 5FUra (100 mg.kg) for the last group in the study. Treating rats with SM and SMN diminished elevating malondialdehyde (MDA) levels, and improved total antioxidant capacity (TAC) levels. Also, the intensity of mRNA expression of interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-α) caused by 5FUra in the gastrointestinal tissue tract, and macroscopic oral ulcerations decreased, ass well as weight loss was prevented, particularly in the SMN group. Moreover, in the microscopic scope, there were significant improvements in the levels of hyperemia, hyaline, and inflammatory cell infiltration in the tongue, esophagus, and intestinal tissues in the FUra + SMN and FUra + SM groups compared to 5FUra. Hence, treatment with SM and SMN reduced oxidative stress, histopathological degeneration, and gene expression of inflammatory markers in the gastrointestinal tract. According to the results, treatment with SM and SMN markedly decreases the gastrointestinal toxicity caused by 5FUra.
5-氟尿嘧啶(5FUra)是治疗实体瘤时使用的第三大最常用化疗成分。在本研究中,我们旨在评估水飞蓟素(SM)和水飞蓟素纳米乳剂(SMN)对成年雄性大鼠5FUra诱导的胃肠道毒性的影响。总共30只雄性Wistar大鼠被分为6组,包括对照组(Crl),以及通过腹腔注射给予SMN(5毫克/千克)、SM(5毫克/千克)、5FUra + SMN(5毫克/千克)和5FUra + SM(5毫克/千克)的组,持续注射14天。对于研究中的最后一组,通过单次腹腔注射5FUra(100毫克/千克)诱导胃肠道毒性。用SM和SMN治疗大鼠可降低丙二醛(MDA)水平的升高,并提高总抗氧化能力(TAC)水平。此外,5FUra在胃肠道组织中引起的白细胞介素-2(IL-2)和肿瘤坏死因子-α(TNF-α)的mRNA表达强度以及宏观口腔溃疡减少,体重减轻也得到预防,尤其是在SMN组。此外,在显微镜下,与5FUra组相比,FUra + SMN组和FUra + SM组的舌、食管和肠道组织中的充血、透明变性和炎症细胞浸润水平有显著改善。因此,用SM和SMN治疗可降低胃肠道的氧化应激、组织病理学变性和炎症标志物的基因表达。根据结果,用SM和SMN治疗可显著降低5FUra引起的胃肠道毒性。