Abstract
Objectives 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.
Conclusion 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.
Keywords
tobacco - cotinine - neuronal degeneration - spinal cord injury
