Formation of methemoglobin by photoactivation of nitrofurantoin or of 5-nitrofurfural in rats exposed to UV-A light.
The antibacterial drug nitrofurantoin (NFT) is notorious for causing hemolytic anemia, which may be related to the methemoglobinemia, another side-effect of NFT. As NFT is photolabile, and nitrite, well known as a MetHb generator, is an important photoproduct of NFT, it seems not unlikely that light is a cause of NFT-induced MetHb formation. When rats were irradiated with UV-A immediately after oral NFT administration, the amount of MetHb significantly increased: 0.97 +/- 0.37% n = 36 (P less than 0.001 Student's t-test, control value: 0.5%). An increase in MetHb was also observed with rats simultaneously exposed to UV-A and the major photodecomposition product of NFT, viz. 5-nitrofurfural. In addition in vitro experiments proved the formation of MetHb as a result of photoactivation of NFT. Nitrite, photochemically formed from nitrofurfural and from the metabolite nitrofuroic acid, plays an important role. A dark reaction of the other photoproduct, nitrofurfural, with hemoglobin also appeared to cause a considerable amount of MetHb in vitro. However, because of rapid deactivation of nitrofurfural by either photodecomposition or metabolism, this dark reaction is not expected to contribute to the in vivo MetHb formation.
Busker
R W
RW
Division of Medicinal Chemistry, Center for Bio-Pharmaceutical Sciences, Leiden, The Netherlands.
Beijersbergen van Henegouwen
G M
GM
Menke
R F
RF
Vasbinder
W
W
D000818:Animals; D005260:Female; D005662:Furaldehyde / Q000031:analogs & derivatives* / Q000097:blood / Q000528:radiation effects / Q000633:toxicity; D005663:Furans / Q000097:blood / Q000528:radiation effects; D008708:Methemoglobinemia / Q000139:chemically induced*; D009582:Nitrofurantoin / Q000097:blood / Q000528:radiation effects* / Q000633:toxicity; D010782:Photolysis; D051381:Rats; D011919:Rats, Inbred Strains; D012977:Sodium Nitrite / Q000097:blood / Q000633:toxicity; D014466:Ultraviolet Rays / Q000009:adverse effects
D005663:Furans; C057339:5-nitro-2-furoic acid; D009582:Nitrofurantoin; D005662:Furaldehyde; D012977:Sodium Nitrite; C052590:5-nitro-2-furaldehyde