Background: A threatening occurrence in some cocaine abusers is the progressive destruction of nasal structures (cocaine-induced midline destructive lesions [CIMDL]) that may end in a highly severe disease.
Methods: Thirty patients with CIMDL, 10 healthy patients, 10 patients affected by nasal polyposis, and 10 patients affected by Wegener granulomatosis were observed. Biopsy specimens of nasal mucosa were analyzed by immunohistochemistry for caspases-3, -9 and -8 and by the terminal deoxynucleotidyl transferase-mediated dUTP-digoxygenin nick end labeling (TUNEL) method. The time and concentration-dependent effects of cocaine in vitro were studied in HaCat cells by TUNEL and Western blotting.
Results: All CIMDL biopsy specimens showed abundant caspase-3 and caspase-9 expression but no caspase-8 positive cells. No obvious expression of any caspases was detected in biopsy specimens from healthy subjects or in patients affected by nasal polyposis or Wegener granulomatosis. In HaCat cells cellular changes were observed, which confirmed induction of massive apoptotic events. The rate of apoptosis in HaCat cells was dependent on the concentration of cocaine. After 1 hour, 2.5, 5, and 10 mM of cocaine induced 16, 45, and 84% of apoptotic figures, respectively, while 6 hours of exposure increased apoptosis to 25, 54, and 94% at the same concentrations. Caspase expression and activation in HaCat cells treated with 100 microM and 1 mM of cocaine for 1 hour were confirmed by Western blotting.
Conclusion: Cultured epithelial cells show both time- and dose-dependent increases in apoptosis and cellular damage on cocaine treatment. We suggest that some abusers trigger CIMDL by abnormally boosting apoptosis within nasal epithelial cells. Cocaine abusers with higher apoptotic rates may predict whether they will eventually develop CIMDL.