Antimutagenesis of beta-carotene to mutations induced by quinolone on Salmonella typhimurium.
BACKGROUND
Quinolone-induced mutagenesis in the Salmonella typhimurium hisG48 strains suggests that these antibiotics are oxygen free radical generators. The use of beta-carotene as antioxidant was evaluated as an alternative to reduce oxidative cell damage in patients who need therapy with nalidixic acid, norfloxacin, or pipemidic acid. The studied beta-carotene (30%), used by pharmaceutical laboratories as dietary complements, was not toxic or mutagenic for the S. typhimurium TA102 strain at a dose equivalent to 1,500 I.U. At the studied concentrations, the evaluated antimutagen did not modify the minimum inhibitory concentration of nalidixic acid, norfloxacin, or pipemidic acid against uropathogenic Escherichia coli strains.


METHODS
The mutagenic effect of nalidixic acid and norfloxacin against hisG48 strains was inhibited with 1500 I.U. of beta-carotene. The antimutagenic effect of beta-carotene against mutations induced by pipemidic acid was observed even with 150 I.U. of beta-carotene. The antimutagenic effect against mutations induced on S. typhimurium TA102 or TA104 strains was observed only when the aroclor 1254 rat-induced liver S9 mixture was used.


RESULTS
This mutagenic effect was detected only when the strains were exposed to quinolones and the beta-carotene simultaneously with the S9 mixture, suggesting that quinolones induce oxygen free radicals that may be scavenged by beta-carotene.


CONCLUSIONS
The antimutagenic effect of this vitamin A precursor is probably due to the active molecule of vitamin A, a desmutagen with the ability of radical capture. A diet rich in beta-carotene or vitamin A could be a good alternative to reduce genotoxic risk to patients being treated with quinolone.
Arriaga-Alba
M
M
Dirección de Investigación y Enseñanza, Hospital Juárez de México, México, D.F., Mexico. arriaga_alba@lettera.net
Rivera-Sánchez
R
R
Parra-Cervantes
G
G
Barro-Moreno
F
F
Flores-Paz
R
R
García-Jiménez
E
E
D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001711:Biotransformation; D004334:Drug Administration Schedule; D005609:Free Radicals; D005798:Genes, Bacterial / Q000187:drug effects*; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009268:Nalidixic Acid / Q000633:toxicity*; D009643:Norfloxacin / Q000633:toxicity*; D018384:Oxidative Stress; D010876:Pipemidic Acid / Q000633:toxicity*; D011355:Prodrugs / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics; D019207:beta Carotene / Q000494:pharmacology*
D016587:Antimutagenic Agents; D005609:Free Radicals; D009153:Mutagens; D011355:Prodrugs; D017382:Reactive Oxygen Species; D019207:beta Carotene; D009268:Nalidixic Acid; D010876:Pipemidic Acid; D009643:Norfloxacin