Department of Toxicology, Jamia Hamdard, New Delhi, Delhi, India.
J Biochem Mol Toxicol. 2022 Nov;36(11):e23187. doi: 10.1002/jbt.23187. Epub 2022 Aug 3.
Lung cancer, one of the most common cancer is a cause of concern associated with cancer-related mortality. Benzo[a]pyrene [B(a)P], a potent carcinogen as well as an environmental contaminant is reported to be found in cigarette smoke among various sources. The present study focuses on the chemopreventive potential of Diosmin against B[a]P-induced lung carcinogenesis and its possible mechanism in male Swiss Albino mice (SAM). SAM were treated orally with Diosmin (200 mg/kg b.w.) for 16 weeks and/or B[a]P (50 mg/kg b.w) for a period of 4 weeks. B[a]P treated cancerous mice showed increased peroxidation of membrane lipid as well as a decrease in the level/activity of antioxidant proteins. Cancerous mice also showed an increased level of carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE). Diosmin treatment, however, leads to decreased peroxidation of lipids, increased antioxidant proteins as well decrease in the level of CEA and NSE. B[a]P-induced cancerous animals also exhibited increased expression of cyclic AMP response element-binding protein (CREB), COX2 as well as prostaglandin-E2 (PGE2) while Diosmin-treated mice were found to have an ameliorative effect. Histopathological results further confirm the protective effect of Diosmin in averting B[a]P-induced pathological alterations of lung tissue. Overall, our results suggest Diosmin exerts its chemopreventive potential possibly via targeting the CREB/cyclooxygenase-2 (COX-2)/PGE2 pathway thereby repressing inflammation.
肺癌是最常见的癌症之一,是与癌症相关的死亡率相关的关注原因之一。苯并[a]芘(B[a]P)是一种有效的致癌物质,也是一种环境污染物,据报道存在于各种来源的香烟烟雾中。本研究集中于地奥司明对 B[a]P 诱导的肺癌发生的化学预防潜力及其在雄性瑞士白化小鼠(SAM)中的可能机制。SAM 经口给予地奥司明(200mg/kg b.w.)16 周和/或 B[a]P(50mg/kg b.w.)4 周。B[a]P 处理的致癌小鼠表现出膜脂质过氧化增加以及抗氧化蛋白的水平/活性降低。致癌小鼠还表现出癌胚抗原(CEA)和神经元特异性烯醇化酶(NSE)水平增加。然而,地奥司明治疗导致脂质过氧化减少,抗氧化蛋白增加,CEA 和 NSE 水平降低。B[a]P 诱导的致癌动物还表现出环磷酸腺苷反应元件结合蛋白(CREB)、COX2 以及前列腺素 E2(PGE2)的表达增加,而地奥司明处理的小鼠表现出改善作用。组织病理学结果进一步证实了地奥司明在避免 B[a]P 诱导的肺组织病理改变方面的保护作用。总体而言,我们的结果表明地奥司明通过靶向 CREB/环加氧酶-2(COX-2)/前列腺素 E2 途径发挥其化学预防潜力,从而抑制炎症。