title: Tobacco-induced neuronal degeneration via cotinine in rats subjected to experimental spinal cord injury.
abstract: OBJECTIVE
  Cigarette smoke contains over 4000 chemicals including well-characterized toxicants and carcinogens, among which is cotinine. Cotinine is the principal metabolite of nicotine that has adverse affects on the microcirculation via vasoconstriction, hypoxia and the wound-healing cascade. Its impact on spinal cord injury (SCI) has not been investigated yet. The aim of the present study is to investigate the cotinine effect on SCI.
  
  
  METHODS
  48 male Wistar rats were divided into six groups as follows: sham-control, sham-trauma, vehicle-control, vehicle-trauma, cotinine-control, and cotinine-trauma. Initially, a defined concentration of cotinine blood level was maintained by daily intraperitoneal injection of cotinine for 14 days in the cotinine groups. The concentration was similar to the cotinine dose in the blood level of heavy smokers. Only ethyl alcohol was injected in the vehicle groups during the same period. Then, SCI was performed by a Tator clip. The cotinine groups were compared with rats subjected to vehicle and sham groups by immunohistochemical biomarkers such as glial fibrillary acidic protein (GFAP) and 2,3-cyclic nucleotide 3-phosphodiesterase (CNP) expressions. Electron microscopic examination was also performed.
  
  
  RESULTS
  GFAP-positive cells were noted to be localized around degenerated astrocytes. Marked vacuolization with perivascular and perineural edema was seen in the cotinin consumption groups. These findings showed the inhibition of regeneration after SCI. Similarly, vacuolization within myelin layers was noted in the cotinine groups, which was detected through reduced CNP expression.
  
  
  CONCLUSIONS
  Cotinine, a main metabolite of nicotine, has harmful effects on SCI via GFAP and CNP expression. The findings of the present study support the hypothesis that tobacco causes neuronal degeneration via cotinine.
authors.affiliation: Neurosurgery Clinic, Ankara Numune Research and Training Hospital, Yenimahalle, Ankara, Turkey. alidalgic@yahoo.com
authors.forename: Ali
authors.initials: A
authors.lastname: Dalgic
authors.forename: Onder
authors.initials: O
authors.lastname: Okay
authors.forename: Fatma
authors.initials: F
authors.lastname: Helvacioglu
authors.forename: Ergun
authors.initials: E
authors.lastname: Daglioglu
authors.forename: Rifat
authors.initials: R
authors.lastname: Akdag
authors.forename: Gulnur
authors.initials: G
authors.lastname: Take
authors.forename: Deniz
authors.initials: D
authors.lastname: Belen
mesh_terms: D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D015415:Biomarkers / Q000378:metabolism; D003367:Cotinine / Q000008:administration & dosage / Q000009:adverse effects*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D046529:Microscopy, Electron, Transmission; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D014947:Wounds and Injuries / Q000150:complications*
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; C571339:Cnp protein, rat; D003367:Cotinine