Biochemical and histomorphological findings in Swiss Wistar rats treated with potential boron-containing therapeutic - K2[B3O3F4OH]

Abstract

Background: Boron and boron containing compounds are known for their biological and protective roles being non-toxic and non-mutagenic in low concentrations. Male rats were exposed to halogenated boroxine (HB), dipotassium-trioxohydroxytetrafluorotriborate K₂[B₃O₃F₄OH], a potential new boron-containing therapeutic, aiming to determine concentrations with no adverse effects on selected serum biochemical parameters and histomorphological features.

Methods: HB was prepared by reacting potassium hydrofluoride (KHF₂) with boric acid in molar ratios 2:3 at room temperature and its primary structure contains 4 fluorine atoms substituted in 6-membered ring. In concentrations of 10, 25, 35 and 45 mg/kg, HB was administered intraperitoneally as a single dose. Biochemical parameters were observed 24 and 96 h following the treatment. Effects of HB on biochemical blood parameters were also observed 24 h following continuous nine days application in concentrations of 10 mg/kg intraperitoneally and 50 mg/kg per os. Histomorphological observation of kidneys, liver, spleen, lungs and heart was performed for all treated animals.

Results: Administration of single high dose of HB (35 mg/kg-45 mg/kg) effected high levels of urea and creatinine, which indicated renal injury that appeared to be temporary. Possible cause of concern is pancreatic injury indicated by elevated levels of serum amylase in the groups of animals that received the highest dosages of the substance. Histopathological examination of selected tissues revealed mild to moderate lesions in the kidneys and livers associated with administration of HB.

Conclusion: Observation of biochemical serum parameters or histopathology of examined tissues revealed no adverse effects of HB either after the administration of single dose lower than 35 mg/kg or following repeated administration at 10 mg/kg. These dosages should be further considered for potential therapeutic applications.

Keywords: Blood parameters; Boron containing compound; Halogenated boroxine; Kidney; Liver.