Effects of pentoxifylline or dexamethasone in combination with amphotericin B in experimental murine cerebral cryptococcosis: evidence of neuroexcitatory pathogenic mechanisms.
In a murine model of intracerebral infection by Cryptococcus neoformans the therapeutic effects of pentoxifylline or dexamethasone were studied alone and in combination with amphotericin B. Assessed parameters were mean survival time, brain histopathology index, amounts of glutamate and gamma-aminobutyric acid in the brain, and yeast CFU per brain. Survival increased significantly in mice treated with dexamethasone, amphotericin B, amphotericin B plus dexamethasone, and amphotericin B plus pentoxifylline; the latter had significantly longer survival than other treated groups. Indices of histopathological damage were similar in all treated groups. In infected untreated mice, the amounts of glutamate in the brain were decreased, presumably by depletion. In mice treated with amphotericin B plus dexamethasone, glutamate levels returned to the range of control mice. No differences in the amounts of gamma-aminobutyric acid were found between control and treatment groups. Brain fungal counts were significantly lower in mice treated with amphotericin B, amphotericin B plus dexamethasone, and amphotericin B plus pentoxifylline than in untreated animals. In this model, pentoxifylline in combination with amphotericin B improved survival, decreasing the fungal burden, and has potential as adjuvant therapy in cerebral cryptococcosis.
Ostrosky-Zeichner
L
L
Department of Neuroimmunology, National Institute of Neurology and Neurosurgery, Mexico City, Mexico.
Soto-Hernandez
J L
JL
Angeles-Morales
V
V
Teixeira
F
F
Nava-Ruiz
C
C
Rios
C
C
Solis
F
F
Sotelo
J
J
D000666:Amphotericin B / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000382:microbiology / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects; D001927:Brain Diseases / Q000188:drug therapy* / Q000503:physiopathology; D003453:Cryptococcosis / Q000188:drug therapy* / Q000503:physiopathology; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D018698:Glutamic Acid / Q000032:analysis; D051379:Mice; D010431:Pentoxifylline / Q000494:pharmacology / Q000627:therapeutic use*; D016019:Survival Analysis; D005680:gamma-Aminobutyric Acid / Q000032:analysis
D000935:Antifungal Agents; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D003907:Dexamethasone; D000666:Amphotericin B; D010431:Pentoxifylline