Toxicology and pharmacology of some euthenium compounds: vascular smooth muscle relaxation by nitrosyl derivatives of ruthenium and iridium

Journal Article · Tue Jul 01 04:00:00 EDT 1980 · J. Toxicol. Environ. Health; (United States)

DOI:https://doi.org/10.1080/15287398009529895· OSTI ID:5219915

Kruszyna, H; Kruszyna, R; Hurst, J; Smith, R P

A series of compounds were synthesized from ruthenium trichloride, and their ip LD50s were determined in mice: pentamminenitrosylruthenium(II) chloride, 8.9; chloronitrobis(2,2'-dipyridyl)ruthenium(II), 55; dichlorobis(2,2'-dipyridyl)ruthenium(II) 63; ruthenium trichloride, 108; and potassium pentachloronitrosylruthenate(II), 127 mg/kg. The two bis-bipyridyl complexes produced death in convulsions within minutes, whereas the remaining compounds resulted in long, debilitating courses with death occuring in 4 to 7 d. When given in massive overdoses, however, the compounds with inorganic ligands also produced rapid convulsive death in mice, and when given iv to anesthetized cats, they produced respiratory arrest. The major toxic effects of all the complexes appeared to be due to the metal and not to its associated ligands. Only complexes having a nitrosyl ligand specifically relaxed vascular smooth muscle. Potassium pentabromoiridate(III) also relaxed rabbit aortic strips that had been contracted by adrenergic argonists, but potassium pentachloroiridate(III) did not. None of the complexes was as active as nitroprusside in relaxing aortic strips or in decreasing arterial blood pressure in cats. No compound tested was as potent as cisplatin in antitumor activity. The pentamminenitrosylruthenium(II) complex also relaxed guinea pig ileum and frog rectus abdominum when these isolated muscles had been contracted by acetylcholine. It appears that these organoruthenium compounds may produce death in central respiratory arrest, as do the inorganic complexes when given iv or ip in massive overdoses. In minimllylethal doses, the complexes with inorganic ligands may affect a variety of contractile tissues, perhaps by a general mechanism involving Ca. These complexes are apt to be generally cytotoxic as well.

• Research Organization: Dartmouth Medical School, Hanover, NH
• OSTI ID: 5219915
• Journal Information: J. Toxicol. Environ. Health; (United States), Journal Name: J. Toxicol. Environ. Health; (United States) Vol. 6:4; ISSN JTEHD
• Country of Publication: United States
• Language: English

Related Subjects

560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMMINES
ANIMALS
BIOLOGICAL EFFECTS
BLOOD VESSELS
BODY
CARDIOVASCULAR SYSTEM
CATS
CHLORIDES
CHLORINE COMPOUNDS
COMPLEXES
ELEMENTS
HALIDES
HALOGEN COMPOUNDS
IRIDIUM
IRIDIUM COMPLEXES
MAMMALS
METALS
MICE
MORTALITY
MUSCLES
ORGANIC COMPOUNDS
ORGANOMETALLIC COMPOUNDS
ORGANS
PHYSIOLOGY
PLATINUM METALS
REFRACTORY METALS
RODENTS
RUTHENIUM
RUTHENIUM CHLORIDES
RUTHENIUM COMPLEXES
RUTHENIUM COMPOUNDS
STRESS RELAXATION
SYNTHESIS
TOXICITY
TRANSITION ELEMENT COMPLEXES
TRANSITION ELEMENT COMPOUNDS
TRANSITION ELEMENTS
VASODILATION
VERTEBRATES