Biomaterial Database

Effect of selenium and vitamin E deficiency on nitrofurantoin toxicity in the chick. 1982

F J Peterson, and G F Combs, and J L Holtzman, and R P Mason

The acute toxicity of nitrofurantoin was studied in the young chick deficient in selenium (Se) and/or vitamin E (E). This new and potentially valuable animal model proved to be very sensitive to the toxicity of this nitro drug. The 48-hour LD50 for nitrofurantoin decreased from 148 mg/kg in the Se- and E-supplemented chicks to 53 mg/kg in Se- and E-deficient chicks. The addition of Se (0.10 ppm as Na2SeO3) alone, but not E (100 IU/kg diet as dl-alpha-tocopheryl acetate) reduced the toxicity of nitrofurantoin, so that the LD50 for the chicks given Se alone was the same as the LD50 for the E- and Se-fed chicks. Se and E deficiency significantly decreased the Se-dependent glutathione peroxidase and the plasma tocopherol levels. Hepatic glutathione content, hepatic catalase and superoxide dismutase were unchanged by the dietary treatments. However, a toxic dose of nitrofurantoin significantly decreased hepatic glutathione content over time. These data support the concept that the toxicity of this drug may be mediated in part by an oxidative stress generated by the futile reductive metabolism of the parent compound.

UI	MeSH Term	Description	Entries
D007928	Lethal Dose 50	The dose amount of poisonous or toxic substance or dose of ionizing radiation required to kill 50% of the tested population.	LD50,Dose 50, Lethal
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D009582	Nitrofurantoin	A urinary anti-infective agent effective against most gram-positive and gram-negative organisms. Although sulfonamides and antibiotics are usually the agents of choice for urinary tract infections, nitrofurantoin is widely used for prophylaxis and long-term suppression.	Furadantin,Furadantine,Furadoine,Furadonine,Furantoin,Macrodantin,Nitrofurantoin Sodium Salt,Nitrofurantoin, Monohydrate
D010544	Peroxidases		Ovoperoxidase
D002374	Catalase	An oxidoreductase that catalyzes the conversion of HYDROGEN PEROXIDE to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in ACATALASIA.	Catalase A,Catalase T,Manganese Catalase,Mn Catalase
D002645	Chickens	Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.	Gallus gallus,Gallus domesticus,Gallus gallus domesticus,Chicken
D004347	Drug Interactions	The action of a drug that may affect the activity, metabolism, or toxicity of another drug.	Drug Interaction,Interaction, Drug,Interactions, Drug
D005978	Glutathione	A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.	Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D005979	Glutathione Peroxidase	An enzyme catalyzing the oxidation of 2 moles of GLUTATHIONE in the presence of HYDROGEN PEROXIDE to yield oxidized glutathione and water.	Cytosolic Glutathione Peroxidase,Glutathione Lipoperoxidase,Selenoglutathione Peroxidase,Glutathione Peroxidase, Cytosolic,Lipoperoxidase, Glutathione,Peroxidase, Glutathione,Peroxidase, Selenoglutathione
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia