Nephrotoxicity of borocaptate after short-term administration in rabbits.
Fifteen Chinchilla rabbits were treated by seven daily i.v. injections of two doses (25 or 50 mg/kg body wt.) of sodium borocaptate (Na2B12H11SH), an agent now widely investigated for potential use in Boron Neutron Capture Therapy (BNCT) of malignant brain tumors. Definite nephrotoxic lesions hyperemic and dilated glomeruli, degenerative necrobiosis with desquamation of tubular epithelium, granular casts in the distal convoluted and collecting tubuli were detected by histopathological examination in the kidneys of all animals without relation to dose of borocaptate. The accumulation of urea in blood and a reduction in red blood cell counts were, however, statistically significant only in rabbits receiving the higher dose (50 mg/kg body wt.) of borocaptate. In the brain the prevalent finding was dilation of perivascular (Virchow-Robin's) spaces. The growth of the animals was retarded and three animals died after injection of the 5th daily dose of borocaptate. With respect to these findings borocaptate sodium can by no means be regarded as an agent which is fully devoid of activity towards healthy non-tumor tissue. Therefore, recent proposals to enhance the effectiveness of BNCT by repeated borocaptate treatment should be considered with caution.
Institute of Pharmacology, Czechoslovak Academy of Sciences, Prague.
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Janků
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Buchar
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Jiricka
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001894:Borohydrides / Q000633:toxicity*; D016754:Boron Neutron Capture Therapy; D002784:Cholesterol / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D011817:Rabbits; D013438:Sulfhydryl Compounds / Q000633:toxicity*; D013997:Time Factors
D001786:Blood Glucose; D001894:Borohydrides; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate; D002784:Cholesterol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin