Susceptibility of mice to bacterial and fungal infections after intragastric administration of ebselen.
The seleno-organic compound ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) has anti-inflammatory activity and exhibits glutathione peroxidase-like activity in-vitro. Ebselen inhibited candidacidal activity over the same range of concentrations as it inhibited the production of microbicidal H2O2 by human neutrophils and macrophage-like cells. Therefore, the long-term administration of ebselen might be expected to induce an immunocompromised state in the host. To examine such a possibility, mice (5-weeks-old ddY, male) were given daily intragastric doses of 0, 10 or 100 mg/kg-1 ebselen for 21 days and then infected intraperitoneally with Candida albicans (10(8) cells/mouse), Pseudomonas aeruginosa (1.5 x 10(7) cells/mouse) or methicillin-resistant Staphylococcus aureus (5 x 10(8) cells/mouse). Ebselen at none of the tested doses affected the increase in body weight of mice during administration of the drug. No evidence was obtained that mice became more susceptible to the various microorganisms after the administration of ebselen at any tested dose.
Nozawa
R
R
Laboratory of Microbiology, University of Shizuoka School of Food and Nutritional Sciences, Shizuoka-shi, Japan.
Arai
M
M
Kuruto
R
R
Motohashi
T
T
Masayasu
H
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D001393:Azoles / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology; D002177:Candidiasis / Q000276:immunology*; D002273:Carcinogens / Q000633:toxicity; D004198:Disease Susceptibility; D005753:Gastric Mucosa / Q000378:metabolism; D018922:HL-60 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007111:Immunity, Cellular / Q000187:drug effects; D054833:Isoindoles; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D016877:Oxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D011552:Pseudomonas Infections / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D013203:Staphylococcal Infections / Q000276:immunology*; D013270:Stomach / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001393:Azoles; D002273:Carcinogens; D054833:Isoindoles; D016566:Organoselenium Compounds; D016877:Oxidants; C042986:ebselen; D006861:Hydrogen Peroxide; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate