Effects of the antituberculous drug ethambutol on zinc balance, distribution, and turnover: short-term studies modeling chronic toxicity

Thesis/Dissertation · Wed Dec 31 23:00:00 EST 1986

OSTI ID:6939458

King, A B

Alterations in Zn metabolism have been reported in both tuberculous patients and experimental animals receiving ethambutol (d-2-2'-ethylenediimino-di-1-butanol dihydrochloride) (EMB), and these changes have been associated with ocular side effects of EMB. EMB has chelating properties but is not likely to chelate Zn at physiologic pH. However, its acid metabolite is a stronger chelator. This research addressed whether EMB affects the absorption and disposition of dietary Zn, and whether effects of EMB on Zn are modified by (a) marginal Zn intake of (b) drugs that may induce metabolism of EMB. Weanling male Sprague-Dawley rats fed an AIN-76A diet received daily by gavage either deionized water or EMB doses of 400-1600 mg/kg bw. in a preliminary, 15-day dose-response study and 400-600 mg/kg in three subsequent 15- to 30-day studies. Apparent absorption and biological turnover of Zn were measured by /sup 65/Zn balance and retention in rats fed adequate (49 ppm) or marginal (11 ppm) Zn. Effects of EMB were similar in both dietary groups. EMB treatment produced alopecia and reduced feed intake, feed efficiency, weight gain, and serum Zn, but showed no effect on hepatic, renal, or femoral Zn concentrations. Absorption, turnover, and urinary excretion of Zn were increased in rats fed EMB.

• Research Organization: Cornell Univ., Ithaca, NY (USA)
• OSTI ID: 6939458
• Country of Publication: United States
• Language: English

Related Subjects

550601 -- Medicine-- Unsealed Radionuclides in Diagnostics
560300* -- Chemicals Metabolism & Toxicology
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY
BODY FLUIDS
CLEARANCE
DAYS LIVING RADIOISOTOPES
DIET
DIGESTIVE SYSTEM
DISTRIBUTION
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
EVEN-ODD NUCLEI
EXCRETION
GLANDS
INTERMEDIATE MASS NUCLEI
ISOTOPES
KIDNEYS
LIVER
MAMMALS
MATERIALS
METABOLISM
NUCLEI
ORGANS
RADIOISOTOPES
RATS
RODENTS
TISSUE DISTRIBUTION
TOXICITY
URINE
VERTEBRATES
WASTES
ZINC 65
ZINC ISOTOPES