Islamov Rinat, Kustova Tatyana, Nersesyan Armen, Ilin Alexander
Scientific Center for Anti-infectious Drugs, Almaty, Kazakhstan.
Institute of Cancer Research, Medical University of Vienna, Vienna, Austria.
Front Vet Sci. 2020 Apr 17;7:184. doi: 10.3389/fvets.2020.00184. eCollection 2020.
Complexes of iodine (povidone-iodine and cadexomers) are among the most important antiseptics used in clinical and veterinary medicines. However, high local irritation activity and systemic toxicity limits their oral administration. The purpose of the study was to compare the effect of a new complex of iodine (PA, potentiator of anticancer antibiotics), in which iodine is coordinated by carbohydrates and polypeptides) on the organisms of rats and dogs treated orally with the drug for 30 days. Wistar rats and Beagle dogs served as experimental animal models. Effect of PA on the animal organism was examined through the measurements of hormones level changes, hematological and clinical chemistry parameters alterations, necropsy and histological examination. The established maximum tolerated dose (MTD) of 2,000 mg/kg PA led to a decrease in the rate of body weight gain in male and female rats. Changes in hematological and certain biochemical parameters in rats at doses of 1,000 and 2,000 mg/kg were observed. Histological study of the thyroid gland revealed changes in the shape and size of the follicles along with colloid resorption. Administration of a half of MTD (180 mg/kg) and lower doses did not result in any change in dogs (thyroid-stimulating hormone, triiodothyronine, and thyroxine). The results of our study show that the pathogenetic action of PA takes place along the path of induction of an inflammatory response with the development of thyrotoxicosis, rather than hypothyroidism. The mechanism of induction of an inflammatory response is also confirmed by histological studies of lesions of the thyroid gland and testes in rats (Figure S1). The no-observed-adverse-effect level (NOAEL) of PA is estimated to be 180 mg/kg (or iodine 22.8 mg/kg) in dogs, which is equivalent to 100 mg/kg (or iodine 12.3 mg/kg) in humans.
碘复合物（聚维酮碘和卡地姆碘）是临床和兽医学中使用的最重要的防腐剂之一。然而，高局部刺激活性和全身毒性限制了它们的口服给药。本研究的目的是比较一种新型碘复合物（PA，抗癌抗生素增效剂，其中碘由碳水化合物和多肽配位）对口服该药物30天的大鼠和犬机体的影响。Wistar大鼠和比格犬作为实验动物模型。通过测量激素水平变化、血液学和临床化学参数改变、尸检和组织学检查来研究PA对动物机体的影响。确定的PA最大耐受剂量（MTD）为2000 mg/kg，导致雄性和雌性大鼠体重增加率下降。在1000和2000 mg/kg剂量下观察到大鼠血液学和某些生化参数的变化。甲状腺组织学研究显示滤泡形状和大小改变以及胶体吸收。给予MTD的一半（180 mg/kg）及更低剂量对犬（促甲状腺激素、三碘甲状腺原氨酸和甲状腺素）没有任何影响。我们的研究结果表明，PA的致病作用是沿着诱导炎症反应并发展为甲状腺毒症的途径发生的,而不是甲状腺功能减退。大鼠甲状腺和睾丸病变的组织学研究也证实了炎症反应的诱导机制（图S1）。PA的未观察到不良反应水平（NOAEL）估计在犬中为180 mg/kg（或碘22.8 mg/kg），相当于人类中的100 mg/kg（或碘12.3 mg/kg）。
