AbdelKader Ghada, Abdelaziz Eman Z, Hassan Ranya, Greish Sahar M, Abogresha Noha M, Sultan Basma O, Yousef Einas M, Morsi Shereen
Department of Human Anatomy and Embryology, Faculty of Medicine, Suez Canal University, Ismailia, EGY.
Department of Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, EGY.
Cureus. 2023 Jan 31;15(1):e34468. doi: 10.7759/cureus.34468. eCollection 2023 Jan.
Among the many known adverse effects of methotrexate (MTX), hepatotoxicity stands out as a major drawback that limits its therapeutic applicability. There is growing evidence that crocin has antioxidant, anti-hyperglycemic, cardioprotective, and anti-inflammatory effects. This study's aim is to evaluate the potential protective effect of crocin against MTX-induced liver damage in rats using biochemical, histological, and immunohistochemical analyses.
Twenty-four adult male albino rats were split into four groups at random (six rats/group) as follows: normal control (saline, intraperitoneal (i.p.) injections), crocin-treated (100 mg/kg daily for 14 days, i.p.), MTX-treated (20 mg/kg single i.p. injection on day 15), and crocin/MTX-treated groups (crocin 100 mg/kg/day for 14 days, i.p. + MTX 20 mg/kg single i.p. injection on day 15). On day 16 of the experiment, blood and tissue specimens were used to assess the liver functions, oxidative stress markers, transforming growth factor beta 1 (), caspase-3, -associated X protein (), and B-cell lymphoma 2 () expression.
The results of the current research revealed the protective actions of crocin against MTX-induced hepatotoxicity. Our results showed that crocin possesses antioxidants (decrease malondialdehyde (MDA), increase glutathione (GSH) levels, and enhance catalase (CAT) and superoxide dismutase (SOD) enzymatic activity), anti-fibrotic (decrease ), and anti-apoptotic (decrease and expression while increase ) actions in liver. Moreover, crocin administration along with MTX restores the normal histological structure of hepatic tissues.
The data presented in the current study using an in vivo animal model support the notion that crocin should be further studied in humans to assess its potential hepatoprotective effects against MTX-induced liver damage.
在甲氨蝶呤（MTX）众多已知的不良反应中，肝毒性是限制其治疗应用的主要缺点。越来越多的证据表明，藏红花素具有抗氧化、抗高血糖、心脏保护和抗炎作用。本研究的目的是通过生化、组织学和免疫组化分析，评估藏红花素对MTX诱导的大鼠肝损伤的潜在保护作用。
将24只成年雄性白化大鼠随机分为四组（每组6只大鼠），如下：正常对照组（腹腔注射生理盐水）、藏红花素治疗组（每天100mg/kg，腹腔注射，共14天）、MTX治疗组（第15天单次腹腔注射20mg/kg）和藏红花素/MTX治疗组（藏红花素100mg/kg/天，腹腔注射，共14天 + 第15天单次腹腔注射MTX 20mg/kg）。在实验的第16天，采集血液和组织样本，评估肝功能、氧化应激标志物、转化生长因子β1（TGF-β1）、半胱天冬酶-3（Caspase-3）、凋亡相关X蛋白（Bax）和B细胞淋巴瘤2（Bcl-2）的表达。
本研究结果揭示了藏红花素对MTX诱导的肝毒性的保护作用。我们的结果表明，藏红花素在肝脏中具有抗氧化作用（降低丙二醛（MDA）水平、增加谷胱甘肽（GSH）水平并增强过氧化氢酶（CAT）和超氧化物歧化酶（SOD）的酶活性）、抗纤维化作用（降低TGF-β1）和抗凋亡作用（降低Bax表达并增加Bcl-2表达）。此外，藏红花素与MTX联合给药可恢复肝组织的正常组织结构。
本研究使用体内动物模型提供的数据支持以下观点，即应在人体中进一步研究藏红花素，以评估其对MTX诱导的肝损伤的潜在肝保护作用。
