Afzal Shekh Mohammad, Vafa Abul, Rashid Summya, Barnwal Preeti, Shahid Ayaz, Shree Alpa, Islam Johirul, Ali Nemat, Sultana Sarwat
Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology & Toxicology, School of Chemical and Life Sciences, New Delhi, India.
Department of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.
Environ Toxicol. 2020 Dec 2. doi: 10.1002/tox.23068.
Hesperidin (HD), a citrus bioflavonoid possesses a variety of biological activities including antioxidant, anti-inflammatory, anti-apoptotic and anti-carcinogenic properties. In the present study, we investigated the effect of HD treatment on N,N'-dimethylhydrazine (DMH) induced oxidative stress, inflammation, apoptosis and goblet cell disintegration in the colon of Wistar rats. Administration of HD was done at two doses (100 and 200 mg/kg body weight) orally to rats daily for 14 days followed by a single subcutaneous injection of DMH (40 mg/kg body weight) on the 14th day and next day animals were sacrificed. The protective potential of HD against colon toxicity was measured through membrane oxidation, antioxidant status, inflammatory and apoptotic markers expression, and histological changes. Results demonstrated that HD inhibited DMH mediated oxidative damage by diminishing the level of peroxidation of lipids and increasing the activity of superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase, glutathione-s-transferase, and glutathione reductase. Moreover, HD attenuated inflammatory (NF-кB, IL-6, and COX-2) and apoptotic (p38-MAPK, p53, and caspase-3) markers expression. HD also attenuated the DMH induced goblet cell disintegration and restored histoarchitecture of the colon. The results of the present study demonstrate that HD efficiently protects against DMH induced colon toxicity by modulating oxidative stress, inflammation, and apoptosis.
橙皮苷（HD）是一种柑橘类生物黄酮，具有多种生物活性，包括抗氧化、抗炎、抗凋亡和抗癌特性。在本研究中，我们调查了HD处理对N，N'-二甲基肼（DMH）诱导的Wistar大鼠结肠氧化应激、炎症、凋亡和杯状细胞解体的影响。以两种剂量（100和200mg/kg体重）给大鼠每日口服HD，持续14天，然后在第14天单次皮下注射DMH（40mg/kg体重），次日处死动物。通过膜氧化、抗氧化状态、炎症和凋亡标志物表达以及组织学变化来测定HD对结肠毒性的保护潜力。结果表明，HD通过降低脂质过氧化水平和增加超氧化物歧化酶、过氧化氢酶、还原型谷胱甘肽、谷胱甘肽过氧化物酶、谷胱甘肽-S-转移酶和谷胱甘肽还原酶的活性，抑制了DMH介导的氧化损伤。此外，HD减弱了炎症（NF-кB、IL-6和COX-2）和凋亡（p38-MAPK、p53和caspase-3）标志物的表达。HD还减轻了DMH诱导的杯状细胞解体，并恢复了结肠的组织结构。本研究结果表明，HD通过调节氧化应激、炎症和凋亡，有效保护大鼠结肠免受DMH诱导的毒性。
