Comparative analysis of morphological and biochemical changes after a single intragastric administration of hybrid organotin compounds

Abstract

Introduction. Organotin compounds are promising candidates for antitumor drugs. Identification of pathogenetic features of the general toxic effect of hybrid organotin compounds during the period of the greatest severity of the intoxication clinical picture will allow to estimate the risk of hepatotoxic and nephrotoxic complications with the administration of bis (3,5–di– tert–butyl–4–hydroxyphenylthiolate) dimethyltin (Me-3) and ((3,5–di–tert–butyl–4–hydroxyphenylthiolate) triphenyltin (M-e5) as chemotherapeutic agents.Аim: To conduct a comparative analysis of morphological and biochemical changes with a single intragastric administration of hybrid organotin compounds Me-3 and Me-5 in the maximum tolerated dose (MTD) on the 7th day of the toxic process development.Material and Methods. Hybrid organotin compounds Me-3 and Me-5 were administered once intragastrically to Wistar rats (females) at a MTD of 2000 mg/kg and 750 mg/kg, respectively. Biochemical and morphological studies were carried out on the 7th day of the development of intoxication symptoms according to standard methods.Results. With the introduction of Me-3 and Me-5 in the liver, signs of fatty dystrophy of varying severity were revealed, with a predominant lesion of centrolobular hepatocytes, an increase in the size of portal tracts due to edema and fibrosis, and scant lymphocytic infiltration. With the introduction of Me-5, morphological changes were more severe, with the involvement of the vascular bed of the organ in the process. When the tested compounds were administered in the kidneys, the same type of damage to the glomerular apparatus and renal tubules was recorded, characteristic of toxic nephropathy. Unidirectional changes in the blood of experimental animals were revealed in the group of nonspecific biochemical markers of cytolysis: a moderate decrease in transaminase activity and an increase in the activity of creatine kinase (CC), lactate dehydrogenase (LDH) and creatinine levels. The process of formation of urea and protein synthesis was functionally preserved.Conclusion. On the 7th day of the development of intoxication with a single intragastric administration of hybrid organotin compounds Me-3 and Me-5 in the maximum tolerated doses, biochemical and morphological changes in the body of animals could be attributed to a moderate degree of severity.