Microscopic studies of the internal organs of rats with prolonged use of phosphonium salt

Abstract

Quaternary phosphonium salts are promising compounds due to their high lipophilicity and membranotropic activity, but data on their chronic toxicity are limited. The aim of the research was to conduct a histological assessment of the chronic toxicity of 3-(decyloxy)-3-oxopropyl triphenylphosphonium chloride with prolonged oral administration. The study was performed on 24 sexually mature white rats (males and females), divided into 4 groups. Animals received a 1 % solution of the compound intragastrically for 30 days at doses of 18,67, 46,67 and 93,34 mg/kg (1/50, 1/20 and 1/10 of LD50). The control group received distilled water. Clinical observation and body weight assessment were performed. After euthanasia, necropsy and histological analysis of organs (liver, lungs, heart, stomach, kidneys, adrenal glands) stained with hematoxylin and eosin were performed. During the experiment, animals of the experimental groups showed a temporary decrease in appetite, and at the maximum dose, a slight loss of body weight and alopecia. Histological analysis showed that the compound in doses up to 93,34 mg/kg does not cause dose-dependent pathological changes in the heart, liver, kidneys, adrenal glands and stomach. The structure of the myocardium, hepatocytes, and nephrocytes remained intact. Background bronchoassociated lymphoid tissue (BALT) and slight thickening of the interalveolar septa were observed in the lungs of all groups, including the control group. In the group with the maximum dose, some animals showed moderate interstitial changes (infiltration by mononuclears and neutrophils), but there were no statistically significant differences from the control (p>0,05), which was regarded as an individual variation against the background of a chronic experiment. It was found that the investigated quaternary phosphonium salt in the studied dose range does not have a systemic toxic effect on parenchymal organs. The revealed pulmonary changes are of a background nature and are not associated with a dose-dependent effect, which justifies the prospects for further study of the compound for practical use.