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

Thesis/Dissertation · Thu Jan 01 00:00:00 EST 1987

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
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

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