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瑞士白化小鼠中叶绿醇和α-红没药醇联合治疗的口服毒性评估及肺癌发生的减轻:对氧化还原酶调节和半胱天冬酶依赖性细胞死亡机制的见解

Oral toxicity assessment and the mitigation of lung carcinogenesis by phytol and α-bisabolol combination treatment in swiss albino mice: insights into redox enzyme modulation and caspase-dependent cell death mechanisms.

作者信息

Kiruthiga Chandramohan, Jafni Sakthivel, Preethi Shankar, Kannan Namasivayam Rajesh, Pandima Devi Kasi

机构信息

Department of Biotechnology, Alagappa University, Karaikudi, 630003, Tamil Nadu, India.

Department of Psychiatry, Government Theni Medical College Hospital, Theni, Tamil Nadu, India.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr;398(4):3881-3894. doi: 10.1007/s00210-024-03484-y. Epub 2024 Oct 5.

Abstract

This study examined the safety and potential anti-lung cancer effects of combinations of phytol and α-bisabolol in Swiss albino mice. Both acute and subacute toxicity assessments showed that the combination of phytol and α-bisabolol is safe, with no adverse effects observed at higher concentrations. Hematological, biochemical, and histopathological tests showed no signs of toxicity in the heart, lungs, liver, spleen, and kidneys. The LD was greater than 2000 mg/kg, indicating a large safety margin. Histopathological analysis confirmed cancer induction in the B(a)P-induced group, which had significantly altered relative lung weights. Lung weight increased slightly pre and post-treatment, but histopathology showed normal alveolar epithelium. GSH and SOD levels increased significantly in B(a)P-exposed groups, indicating an adaptive antioxidant response. CAT levels increased significantly in the post-treatment group, demonstrating the role of combination of phytol and α-bisabolol in protecting against B(a)P-induced oxidative damage. Upregulation of Bax and downregulation of Bcl-2 caused a pro-apoptotic environment, suggesting a way to inhibit malignant cell survival. Modulation of caspase-3 and caspase-9 showed the complexity of carcinogen-induced apoptotic signaling. In conclusion, phytol and α-bisabolol were found to be safe and organ-protective, and demonstrated no acute or subacute toxicity. They modulate antioxidant defenses and apoptotic pathways, which may help prevent and treat lung cancer.

摘要

本研究考察了叶绿醇与α-红没药醇联合用药对瑞士白化小鼠的安全性及潜在的抗肺癌作用。急性和亚急性毒性评估均表明,叶绿醇与α-红没药醇联合用药是安全的,在较高浓度下未观察到不良反应。血液学、生物化学和组织病理学检测显示,心脏、肺、肝脏、脾脏和肾脏均无中毒迹象。半数致死量大于2000 mg/kg,表明安全范围较大。组织病理学分析证实,苯并(a)芘诱导组出现了癌症诱发情况,其相对肺重量有显著改变。治疗前后肺重量略有增加,但组织病理学显示肺泡上皮正常。苯并(a)芘暴露组的谷胱甘肽(GSH)和超氧化物歧化酶(SOD)水平显著升高,表明存在适应性抗氧化反应。治疗后组的过氧化氢酶(CAT)水平显著升高,证明了叶绿醇与α-红没药醇联合用药在预防苯并(a)芘诱导的氧化损伤中的作用。Bax上调和Bcl-2下调导致促凋亡环境,提示了一种抑制恶性细胞存活的方法。半胱天冬酶-3和半胱天冬酶-9的调节显示了致癌物诱导的凋亡信号传导的复杂性。总之,叶绿醇和α-红没药醇被发现是安全的且具有器官保护作用,未表现出急性或亚急性毒性。它们调节抗氧化防御和凋亡途径,这可能有助于预防和治疗肺癌。

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