Role of metabolism in N-methylthiobenzamide-induced pneumotoxicity

Journal Article · Wed May 01 04:00:00 EDT 1985 · Toxicol. Appl. Pharmacol.; (United States)

DOI:https://doi.org/10.1016/0041-008X(85)90237-6· OSTI ID:6285091

Penney, D A; Gottschall, D W; Hanzlik, R P; Traiger, G J

N-Methylthiobenzamide (NMTB) produces pulmonary edema, hydrothorax, and death in rodents. The objectives of the present studies were to establish a relationship between the lethality of NMTB and its pneumotoxicity and to explore the role of S-oxidation in these events. Pulmonary injury was assessed by measuring ( UC)thymidine incorporation into pulmonary DNA. Administration of NMTB resulted in increased pulmonary ( UC)thymidine incorporation in both rats and mice. These increases were blocked in both species by pretreatment of animals with sublethal doses of NMTB. However, the lethality of NMTB was not blocked in mice by prior administration of NMTB even though this procedure has been shown to protect rats. 1-Methyl-1-phenyl-3-benzoylthiourea (MPBTU) protected both rats and mice from lethal doses of NMTB and blocked NMTB-induced increases in pulmonary ( UC)thymidine incorporation. N-Methylthiobenzamide S-oxide (NMTBSO), a metabolite of NMTB, produced lung injury which was similar to that produced by NMTB. NMTBSO was more potent than NMTB when administered iv, but not when given ip. The role of hepatic metabolism in NMTB pneumotoxicity was examined by administering NMTB to rats which had either undergone partial hepatectomy or been pretreated with N-octylimidazole. Neither of these procedures diminished the lethality of NMTB. These data suggest that NMTB lethality is mediated by pulmonary injury resulting from NMTB S-oxidation in the lung.

• Research Organization: Univ. of Kansas, Lawrence
• OSTI ID: 6285091
• Journal Information: Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 3; ISSN TXAPA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMIDES
ANIMALS
ANTITHYROID DRUGS
AZINES
BIOLOGICAL EFFECTS
BODY
CARBON 14 COMPOUNDS
CARBONIC ACID DERIVATIVES
CHEMICAL REACTIONS
DIGESTIVE SYSTEM
DNA
DRUGS
EDEMA
GLANDS
HEPATECTOMY
HETEROCYCLIC COMPOUNDS
HORMONE ANTAGONISTS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIVER
LUNGS
MAMMALS
MEDICINE
MICE
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
OXIDATION
PATHOLOGICAL CHANGES
PYRIMIDINES
RATS
RESPIRATORY SYSTEM
RIBOSIDES
RODENTS
SURGERY
SYMPTOMS
THIOUREA
THIOUREAS
THYMIDINE
TRACER TECHNIQUES
VERTEBRATES