实验条件下莫西多明与ATP-LONG单次重复联合的药理学毒性评价

L. Kuprash, T. Panteleymonova, L. Sharabura, S. Mykhalskiy, P. Klymenko, Sergey S. Lugovskoy, V. Nepomnyashchy, N. Sykalo, V. Bezrukov
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引用次数: 0

摘要

摘要这项工作的目的是研究新的联合药物的毒性,该药物由硝基血管扩张剂莫西多明和腺苷- 5 ' -三磷酸与组氨酸、镁和钾(ATP-LONG)配位化合物组成。经口给药(p/o)和舌下给药(s/l)对Balb/c小鼠和Wistar育龄大鼠进行急性和亚急性毒性试验。经测定,该物质的LD50大于10000mg /kg (p/o)和5010mg /kg (s/l),属于实际无毒物质。有条件治疗剂量260 mg/hg (s/l)在28天内重复给药,对雌雄大鼠的生理、生化和组织学指标均无负面影响。在1300和2080 mg/kg的剂量下,超过有条件治疗剂量的5倍和8倍,联合用药没有改变大鼠的临床实验室尿液和血液值,但引起组织学改变,如毛细血管扩张和过多,以及脑、心肌、肝、脾、肾和肾上腺的平滑肌细胞水肿。此外,这种组合物质的特定剂量会刺激舌头的粘膜。检测到的药物效应不携带任何病理特征,可以看作是机体对高剂量硝基血管扩张剂的特异性反应。然而,莫西多明过量,特别是其联合形式的不良后果的持续时间和可逆性,需要进一步研究。关键词:莫西多明与ATP-LONG联用,急性和亚急性毒性
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Pharmacology-based toxicity assessment of molsidomine and ATP-LONG combination with singular and repetitive injections under experimental conditions
Abstract. The aim of the work was to study toxic properties of the new combined drug which comprise nitrovasodilator molsidomine and adenosine- 5’-triphosphate in a form of coordination compound with histidine, magnesium, and potassium (ATP-LONG). The drug was examined for its acute and subacute toxicity on Balb/c mice and Wistar rats of reproductive age with peroral (p/o) and sublingual (s/l) administrations. It has been established that LD50 of the substance contains over 10000 mg/kg (p/o) and 5010 mg/kg (s/l), which corresponds to the category of Practically non-toxic substances. The repetitive administrations within a 28 day period of the conditionally therapeutic dose of 260 mg/hg (s/l) did not cause any negative impact on physiological, biochemical, histological values in male and female rats. In doses 1300 and 2080 mg/kg, which exceed conditionally therapeutic doses by 5 and 8 times, the combination was not changing clinical laboratory urine and blood values but induced histological changes such as dilation and plethora of capillaries along with edema of smooth muscle cells of the brain, myocardium, liver, spleen, kidneys, and adrenal glands in rats. Additionally, the particular dosages of the combined substance provoked irritation of the mucous membrane of the tongue. Detected effects of the drug do not carry any pathological character and can be viewed as a specific reaction of the organism to high doses of nitrovasodilator. However, the duration and reversibility of unwanted consequences of molsidomine overdose, particularly in its combined form, need further investigation. Keywords: combination of molsidomine and ATP-LONG, acute and subacute toxicity
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