Department of Toxicology, Jamia Hamdard, New Delhi, India.
Department of Oncology, PGIMS-Rohtak, Rohtak, India.
Environ Toxicol. 2022 Sep;37(9):2153-2166. doi: 10.1002/tox.23558. Epub 2022 May 14.
1,2-Dimethylhydrazine (DMH), a colon-specific environmental toxicant is one among the carcinogen responsible for the cause of colon cancer. The present study was designed to evaluate the protective effect of Hesperetin (HST) against colon toxicity induced by DMH in Wistar rats. HST, a flavonoid widely found in citrus fruits possesses several biological activities including anti-microbial, anti-oxidant properties among others. A single dose of DMH (40 mg/kg body weight) was administered subcutaneously on 1st day for induction of colon toxicity followed by oral treatment with HST at a dose of 20 mg/kg bodyweight for 14 consecutive days. DMH administration leads to excessive ROS generation, resulting in an imbalance in redox homeostasis and causing membrane lipid peroxidation, which is also partly due to the decrease in the level of tissue antioxidant machinery. Our result showed HST significantly ameliorates DMH-induced lipid peroxidation and also substantially increases the activity/level of various anti-oxidant proteins (GR, GPx, GST, GSH, and SOD). HST was also found to reduce the expression of inflammatory proteins (TNF-α, IL-6, i-NOS, COX-2, NF-kB-p65), goblet cell disintegration as well as mucin depletion (sulfo and sialomucin) in the colon that was found to be elevated upon administration of DMH. Our histological results further provide confirmation of the protective role of HST against DMH-induced pathological alterations. The results of the present study demonstrate supplementation of HST is beneficial in ameliorating DMH-induced toxicity by suppressing oxidative stress, inflammation, goblet cell disintegration as well mucin depletion in the colon of Wistar rats.
1,2-二甲基肼（DMH）是一种结肠特异性环境毒物，是导致结肠癌的致癌物质之一。本研究旨在评估橙皮苷（HST）对 DMH 诱导的 Wistar 大鼠结肠毒性的保护作用。HST 是一种广泛存在于柑橘类水果中的类黄酮，具有多种生物学活性，包括抗菌、抗氧化等。在第 1 天，通过皮下注射给予大鼠单次剂量的 DMH（40mg/kg 体重）以诱导结肠毒性，然后连续 14 天口服 HST 治疗，剂量为 20mg/kg 体重。DMH 给药会导致过量的 ROS 生成，导致氧化还原平衡失衡并引起膜脂质过氧化，这部分也是由于组织抗氧化机制水平的降低所致。我们的结果表明，HST 显著改善了 DMH 诱导的脂质过氧化，还大大增加了各种抗氧化蛋白（GR、GPx、GST、GSH 和 SOD）的活性/水平。还发现 HST 降低了促炎蛋白（TNF-α、IL-6、i-NOS、COX-2、NF-kB-p65）的表达，减少了结肠中炎性细胞的破坏以及粘蛋白的耗竭（硫酸和唾液粘蛋白），而这些在给予 DMH 后会升高。我们的组织学结果进一步证实了 HST 对 DMH 诱导的病理改变具有保护作用。本研究的结果表明，补充 HST 通过抑制氧化应激、炎症、结肠杯状细胞破坏以及粘蛋白耗竭，有利于改善 DMH 诱导的毒性。
