Jagetia Ganesh Chandra, Shirwaikar Annie, Rao Shaival K, Bhilegaonkar Prasad M
Department of Radiobiology, Kasturba Medical College, Manipal 576 119, India.
J Pharm Pharmacol. 2003 Aug;55(8):1151-8. doi: 10.1211/0022357021576.
The effect of various doses (0, 25, 50, 75, 100, 125, 150, 300, 600 and 900 mg kg(-1)) of the alcoholic extract of the plant Ageratum conyzoides Linn. (ACE), on the alteration of radiation-induced mortality in mice exposed to 10 Gy of gamma radiation was studied. The acute toxicity studies showed that the drug was non-toxic up to a dose of 3000 mg kg(-1), the highest dose that could be tested for acute toxicity. Administration of ACE resulted in a dose-dependent decline in radiation-induced mortality up to a dose of 75 mg kg(-1), the dose at which the highest number of survivors (70.83%) was observed. Thereafter, the number of survivors declined with increasing doses of ACE and a nadir was reached at 900 mg kg(-1) ACE. Since the number of survivors was highest for 75 mg kg(-1) ACE, this was considered the optimum dose for radioprotection and used in further studies in which mice were treated with 75 mg kg(-1) ACE before exposure to 6, 7, 8, 9, 10 and 11 Gy of gamma radiation. The treatment of mice with 75 mg kg(-1) ACE reduced the severity of symptoms of radiation sickness and mortality at all exposure doses, and a significant increase in survival was observed compared with the non-treated irradiated group. The ACE treatment effectively protected mice against the gastrointestinal as well as bone marrow related death, as revealed by the increased number of survivors at all irradiation doses. The dose reduction factor was found to be 1.3. To understand the mechanism of action, various doses of ACE were evaluated for their in-vitro scavenging action on 1,1-diphenyl-2-picrylhydrazyl (DPPH), a chemically stable free radical. ACE was found to scavenge DPPH radicals in a concentration-dependent manner, indicating that the radioprotection afforded by ACE may be in part due to the scavenging of reactive oxygen species induced by ionizing radiation.
研究了不同剂量(0、25、50、75、100、125、150、300、600和900毫克/千克)的藿香蓟(Ageratum conyzoides Linn.)酒精提取物(ACE)对接受10戈瑞γ射线照射的小鼠辐射诱导死亡率变化的影响。急性毒性研究表明,该药物在高达3000毫克/千克的剂量下无毒,这是可用于急性毒性测试的最高剂量。给予ACE导致辐射诱导死亡率呈剂量依赖性下降,直至75毫克/千克的剂量,在此剂量下观察到存活小鼠数量最多(70.83%)。此后,随着ACE剂量的增加,存活小鼠数量下降,在900毫克/千克的ACE剂量下达到最低点。由于75毫克/千克的ACE剂量下存活小鼠数量最多,因此该剂量被认为是辐射防护的最佳剂量,并用于进一步研究,在这些研究中,小鼠在接受6、7、8、9、10和11戈瑞γ射线照射前用75毫克/千克的ACE进行处理。用75毫克/千克的ACE处理小鼠可降低所有照射剂量下辐射病症状的严重程度和死亡率,与未处理的照射组相比,观察到存活率显著提高。ACE处理有效地保护小鼠免受胃肠道和骨髓相关死亡,这在所有照射剂量下存活小鼠数量的增加中得到体现。发现剂量降低因子为1.3。为了解其作用机制,评估了不同剂量的ACE对1,1-二苯基-2-苦基肼(DPPH)(一种化学稳定的自由基)的体外清除作用。发现ACE以浓度依赖性方式清除DPPH自由基,表明ACE提供的辐射防护可能部分归因于对电离辐射诱导的活性氧的清除。