An assessment of the role of redox cycling in mediating the toxicity of paraquat and nitrofurantoin

Journal Article · Sat Mar 31 23:00:00 EST 1990 · Environmental Health Perspectives; (USA)

DOI:https://doi.org/10.2307/3430673· OSTI ID:6287445

Adam, A; Cohen, G M ^[1]; Smith, L L ^[2]

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1. Univ. of London (England)
2. Imperial Chemical Industries plc, Cheshire (England)

The abilities of paraquat, diquat, and nitrofurantoin to undergo cyclic oxidation and reduction with rat microsomal systems have been assessed and compared to that of the potent redox cycler, menadione. Diquat and menadione were found to be potent redox cyclers with comparable abilities to elicit a nonstoichiometric increase in both the consumption of O{sub 2} and the oxidation of NADPH, compared to the amounts of substrate added. In contrast, paraquat and nitrofurantoin redox cycled poorly, being an order of magnitude less potent than either diquat or menadione. This was reflected in kinetic studies using lung and liver microsomes. In order to assess redox cycling of the substrates in an intact lung system, the O{sub 2} consumption of rat lung slices was measured in the presence of all four compounds. A small increase in lung slice O{sub 2} uptake was observed with paraquat in the first 2.5 hr of incubation, possibly because of redox cycling of a high intracellular concentration of paraquat resulting from active accumulation into target cells. This stimulation in O{sub 2} uptake was no longer observed when slices were incubated for a longer period or with higher paraquat concentrations (10{sup {minus}4}M), possibly because of toxic effects in target cells. These results together with the poor ability to redox cycle with microsomes and the absence of a specific uptake system highlight the problem of associating redox cycling and oxidative stress in the mechanism of nitrofurantoin toxicity.

• OSTI ID: 6287445
• Journal Information: Environmental Health Perspectives; (USA), Journal Name: Environmental Health Perspectives; (USA) Vol. 85; ISSN 0091-6765; ISSN EVHPA
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AZINES
AZOLES
BIOCHEMICAL REACTION KINETICS
BIPYRIDINES
BODY
CELL CONSTITUENTS
CHEMICAL REACTIONS
DIGESTIVE SYSTEM
DOSE-RESPONSE RELATIONSHIPS
ELEMENTS
GLANDS
HETEROCYCLIC COMPOUNDS
HYDANTOINS
IMIDAZOLES
KINETICS
LIVER
LUNGS
MICROSOMES
NONMETALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
ORGANS
OXYGEN
PYRIDINES
REACTION KINETICS
REDOX REACTIONS
RESPIRATORY SYSTEM
RIBOSOMES
TOXICITY