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Subchronic Toxicity of the New Iodine Complex in Dogs and Rats.

ABSTRACT: Background: 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. Methods: 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. Results: 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). Conclusions: 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.

SUBMITTER: Islamov R

PROVIDER: S-EPMC7181231 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Subchronic Toxicity of the New Iodine Complex in Dogs and Rats.

Islamov Rinat R Kustova Tatyana T Nersesyan Armen A Ilin Alexander A

Frontiers in veterinary science 20200417

<b>Background:</b> 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 d ...[more]

PMID: 32363201

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Project description:Background:Combretum micranthum (CM) (Combretaceae) is widely used in traditional medicine throughout West Africa for the treatment of diabetes, hypertension, inﬂammation, malaria and liver ailments. In our recent research we demonstrated that CM has nephroprotective potentials in diabetes mellitus, hypertension and renal disorders. However, to the best of our knowledge, no systematic study concerning its toxicity proﬁle has been reported. Aim of the study:The study carried out to evaluates the potential toxicity of the hydroalcoholic extract from leaves of the CM, through the method of acute and sub-chronic oral administration in rats. Materials and methods:During the acute toxicity study, male and female rats were orally administrated with CM extract at single doses of 5000 mg/kg (n = 5/group/sex). Abnormal behaviour, toxic symptoms, weight, and death were observed for 14 consecutive days to assess the acute toxicity. For sub-chronic toxicity study, the extract was administered orally at doses of 500 and 1000 mg/kg (n = 5/group/sex) daily to Wistar rats for 28 days. The general behaviour and body weight of the rats was observed daily. A biochemical, haematological, macroscopical and histopathological examinations of several organs were conducted at the end of the treatment period. The CM extract was subjected to Fourier transform infrared spectrophotometric examination in order to detect the presence or absence of cyanide toxic compounds. Results:The absence of absorbance peaks between the 2220-2260 cm-1 region of FT-IR spectrum of CM, indicating the absence of cyanide groups. This suggested that the CM extract may not contain toxic substances. During the acute toxicity test, no mortality or adverse effects were noted at the dose of 5000 mg/kg. In the subchronic study, the CM extract induced no mortality or treatment-related adverse effects with regard to body weight, general behaviour, relative organ weights, hematological, and biochemical parameters. Histopathological examination of vital organs showed normal architecture suggesting no morphological alterations. Conclusion:The present study revealed that oral administration of CM extract for 28 days, at dosage up to 1000 mg/kg did not induce toxicological damage in rats. From acute toxicity study, the median lethal dose (LD50) of the extract was estimated to be more than 5000 mg/kg.

Project description:Chronic respiratory disease is among the most common non-communicable diseases, and particulate materials (PM) are a major risk factor. Meanwhile, evidence of the relationship between the physicochemical characteristics of PM and pulmonary toxicity mechanism is still limited. Here, we collected particles (CPM) from the air of a port city adjacent to a cement factory, and we found that the CPM contained various elements, including heavy metals (such as arsenic, thallium, barium, and zirconium) which are predicted to have originated from a cement plant adjacent to the sampling site. We also delivered the CPM intratracheally to mice for 13 weeks to investigate the pulmonary toxicity of inhaled CPM. CPM-induced chronic inflammatory lesions with an increased total number of cells in the lung of mice. Meanwhile, among inflammatory mediators measured in this study, levels of IL-1β, TNF-α, CXCL-1, and IFN-γ were elevated in the treated group compared with the controls. Considering that the alveolar macrophage (known as dust cell) is a professional phagocyte that is responsible for the clearance of PM from the respiratory surfaces, we also investigated cellular responses following exposure to CPM in MH-S cells, a mouse alveolar macrophage cell line. CPM inhibited cell proliferation and formed autophagosome-like vacuoles. Intracellular calcium accumulation and oxidative stress, and altered expression of pyrimidine metabolism- and olfactory transduction-related genes were observed in CPM-treated cells. More interestingly, type I-LC3B and full-length PARP proteins were not replenished in CPM-treated cells, and cell cycle changes, apoptotic and necrotic cell death, and caspase-3 cleavage were not significantly detected in cells exposed to CPM. Taken together, we conclude that dysfunction of alveolar macrophages may contribute to CPM-induced pulmonary inflammation. In addition, given the possible transformation of heart tissue observed in CPM-treated mice, we suggest that further study is needed to clarify the systemic pathological changes and the molecular mechanisms following chronic exposure to CPM.

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Subchronic Toxicity of the New Iodine Complex in Dogs and Rats.

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Subchronic Toxicity of the New Iodine Complex in Dogs and Rats.

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