Periferik Sinir Yaralanmalarında Kotinin Etkileri: Deneysel Bir Çalışma
Year 2021,
Volume: 23 Issue: 2, 157 - 163, 30.08.2021
Rıfat Akdağ
,
Ali Dalgıç
,
Gülnur Take
Uğur Soylu
,
Emin Çağıl
Abstract
Amaç: Sigara içmek yaygın bir bağımlılık biçimidir ve sağlık için en büyük tehditlerden biridir. Nikotin, sigaranın ana bileşenlerinden biridir. Bu çalışmanın amacı, nikotinin aktif bir metaboliti olan kotininin sıçanlarda periferik sinir hasarına etkisini ortaya koymaktır.
Gereç ve Yöntemler: Basit randomizasyon metoduyla üç gruba ayrılan 42 erkek yetişkin albino-Wistar sıçan üzerinde çalıştık. Grup 1'e 21 gün boyunca 0,3 mg/kg/gün dozunda intraperitoneal olarak Cotinine® (C-5923-sigma) verildi. Grup 2'ye aynı şekilde Cotinine çözücüsü olan etil alkol, aynı doz ve sürede verildi. Grup 3, kapanma basıncı 50 gr/cm2 olan klips ile siyatik sinir kompresyonu yaralanmasına maruz bırakıldı. Grup 1 ve 2 ise 21 gün sonunda aynı tipte yaralanmaya maruz bırakıldı. Travmadan dört hafta sonra bütün gruplar sakrifiye edildi ve hasarlı siyatik sinir kesitleri histopatolojik analiz için alındı.
Bulgular: Kotininin travmatik dejenerasyonu şiddetlendirdiği gözlenmiştir ve ayrıca kotininin özellikle fibrozun artışına neden olduğu görülmüştür. Kalın miyelinli fiberlerdeki Schwann hücrelerinde daha yüksek derecelerde dejenerasyona sebep olduğu ve ek olarak, bu hücrelerde mitokondriyal artış olduğu görüldü. Çoklu karşılaştırma sonuçlarına göre travma grubunda Wallerian dejenerasyon sayısı hem ilaç kontrol (p=0,016) grubu hem de ilaç grubuna (p<0,001) göre anlamlı derecede daha düşüktü. Bu durumun oksidatif strese bir yanıt olarak geliştiği tahmin edilmektedir.
Sonuç: Bu çalışma, sigara içenlerde travmatik yaralanma sonrası periferik sinir yenilenmesinin olumsuz şekilde etkilenebileceğini ortaya koymaktadır.
References
- Warren CW, Jones NR, Eriksen MP, Asma S. Patterns of global tobacco use in young people and implications for future chronic disease burden in adults. Lancet. 2006;367(9512):749-53.
- Benner CL, Bayona JM, Caka FM, Tang H, Lewis L, Crawford J, et al. Chemical composition of environmental tobacco smoke and two particulate-phase compounds. Environ Sci Technol. 1986;23(6):688-99.
- Kawachi I, Colditz GA. Invited commentary: confounding, measurement error, and publication bias in studies of passive smoking. Am J Epidemiol. 1996;144(10):909-15.
- Hegaard HK, Kjaergaard H, Møller LF, Wachmann H, Ottesen B. Determination of a saliva cotinine cut-off to distinguish pregnant smokers from pregnant non-smokers. Acta Obstet Gynecol Scand. 2007;86(4):401-6.
- DeLorenze GN, Kharrazi M, Kaufman FL, Eskenazi B, Bernert JT. Exposure to environmental tobacco smoke in pregnant women: the association between self-report and serum cotinine. Environ Res. 2002;90(1):21-32.
- Rodriguez-Fontan F, Reeves B, Tuaño K, Colakoglu S, D' Agostino L, Banegas R. Tobacco use and neurogenesis: A theoretical review of pathophysiological mechanism affecting the outcome of peripheral nerve regeneration. J Orthop. 2020;22:59-63.
- Benowitz NL, Jacob P 3rd, Fong I, Gupta S. Nicotine metabolic profile in man: comparison of cigarette smoking and transdermal nicotine. J Pharmacol Exp Ther. 1994;268(1):296-303.
- Benowitz NL, Jacob P 3rd. Metabolism of nicotine to cotinine studied by a dual stable isotope method. Clin Pharmacol Ther. 1994;56(5):483-93.
- Simske NM, Krebs JC, Heimke IM, Scarcella NR, Vallier HA. Nerve injury with acetabulum fractures: Incidence and factors affecting recovery. J Orthop Trauma. 2019;33(12):628-34.
- Ding ZM, Gao Y, Sentir AM, Tan X. Self-administration of cotinine in Wistar rats: Comparisons to nicotine. J Pharmacol Exp Ther. 2021;376(3):338-47.
- Lewis DF, Dickins M, Lake BG, Eddershaw PJ, Tarbit MH, Goldfarb PS. Molecular modelling of the human cytochrome P450 isoform CYP2A6 and investigations of CYP2A substrate selectivity. Toxicology. 1999;133(1):1-33.
- Visoni S, Meireles N, Monteiro L, Rossini A, Pinto LF. Different modes of inhibition of mouse Cyp2a5 and rat CYP2A3 by the food-derived 8-methoxypsoralen. Food Chem Toxicol. 2008;46(3):1190-5.
- Benowitz NL. Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiol Rev. 1996;18(2):188-204.
- Caldwell WS, Greene JM, Byrd GD, Chang KM, Uhrig MS, deBethizy JD, et al. Characterization of the glucuronide conjugate of cotinine: A previously unidentified major metabolite of nicotine in smokers’ urine. Chem Res Toxicol. 1992;5(2):280-5.
- Hammond SK, Leaderer BP. A diffusion monitor to measure exposure to passsive smoking. Environ Sci Technol. 1987;21(5):494-7.
- Nakajima M, Fukami T, Yamanaka H, Higashi E, Sakai H, Yoshida R, et al. Comprehensive evaluation of variability in nicotine metabolism and CYP2A6 polymorphic alleles in four ethnic populations. Clin Pharmacol Ther. 2006;80(3):282-97.
- Hukkanen J, Jacob P 3rd, Benowitz NL. Effect of grapefruit juice on cytochrome P450 2A6 and nicotine renal clearance. Clinical Pharmacol Ther. 2006;80(5):522-30.
- de Leon J, Diaz FJ, Rogers T, Browne D, Dinsmore L, Ghosheh OH, et al. Total cotinine in plasma: a stable biomarker for exposure to tobacco smoke. J Clin Psychopharmacol. 2002;22(5):496-501.
- Li Y, Bickel KD, Im MJ, Hu L, Dellon AL, Vander Kolk CA, et al. Effects of deferoxamine on ischemia/reperfusion injury after peripheral nerve compression. Ann Plast Surg. 1996;36(4):365-9.
- Macchi MM, Bruce JN. Human pineal physiology and functional significance of melatonin. Front Neuroendocrinol. 2004;25(3-4):177-95.
- Zhang YL, Zhang PB, Qiu SD, Liu Y, Tian YF, Wang Y. Effects of ketamine-midazolam anesthesia on the expression of NMDA and AMPA receptor subunit in the peri-infarction of rat brain. Chin Med J (Engl). 2006;119(18):1555-62.
- Túnez I, Montilla P, Muñoz MC, Drucker-Colín R. Effect of nicotine on 3 nitropropionic acid-induced oxidative stress in synaptosomes. Eur J Pharmacol. 2004;504(3):169-75.
- Paquette ST, Dawes RP, Sundar IK, Rahman I, Brown EB, White PM. Chronic cigarette smoke exposure drives spiral ganglion neuron loss in mice. Sci Rep. 2018;8(1):5746.
- Camp CL, Ryan CB, Degen RM, Dines JS, Altchek DW, Werner BC. Risk factors for revision surgery following isolated ulnar nerve release at the cubital tunnel: A study of 25,977 cases. J Shoulder Elbow Surg. 2017;26(4):710-5.
- Santiago HA, Zamarioli A, Sousa Neto MD, Volpon JB. Exposure to secondhand smoke impairs fracture healing in rats. Clin Orthop Relat Res. 2017;475(3):894-902.
- Andersen AM, Lei MK, Beach SRH, Philibert RA. Inflammatory biomarker relationships with helper T cell GPR15 expression and cannabis and tobacco smoking. J Psychosom Res. 2021;141:110326.
- Chen LE, Seaber AV, Glisson RR, Davies H, Murrell GA, Anthony DC, et al. The functional recovery of peripheral nerves following defıned acute crush injuries. J Orthop Res. 1992;10(5):657-64.
- Kasahara K, Nakagawa T, Kubota T. Neuronal loss and expression of neurotrophic factors in a model of rat chronic compressive spinal cord injury. Spine (Phila Pa 1976). 2006;31(18):2059-66.
- Boiangiu RS, Mihasan M, Gorgan DL, Stache BA, Hritcu L. Anxiolytic, promnesic, anti-acetylcholinesterase and antioxidant effects of Cotinine and 6-hydroxy-L-nicotine in scopolamine-induced zebrafish (Danio rerio) model of alzheimer's disease. Antioxidants (Basel). 2021;10(2):212.
- Sayan H, Ozacmak VH, Özen OA, Coskun O, Arslan SO, Sezen SC, et al. Benefıcial effects of melatonin on reperfusion injury in rat sciatic nerve. J Pineal Res. 2004;37(3):143-8.
- Cheeseman KH, Slater TF. An introduction to free radical biochemistry. Br Med Bull. 1993;49(3):481-43.
Cotinine Effects on Peripheral Nerve Injuries: An Experimental Study
Year 2021,
Volume: 23 Issue: 2, 157 - 163, 30.08.2021
Rıfat Akdağ
,
Ali Dalgıç
,
Gülnur Take
Uğur Soylu
,
Emin Çağıl
Abstract
Aim: Cigarette smoking is a common addictive manner and one of the greatest threats to health. Nicotine is one of the main components of cigarette. The aim of this study was to reveal the effect of cotinine which is an active metabolite of nicotine, on peripheral nerve injury in rats.
Material and Methods: We studied 42 male adult albino-Wistar rats that were divided into three groups with simple randomization method. Group 1 were given Cotinine® (C-5923-sigma) intraperitoneally, at a dose of 0.3 mg/kg/day for 21 days. Group 2 were given ethyl alcohol, the solvent of Cotinine in the same way, dose and period. Group 3 were subjected to sciatic nerve compression injury by a clip, which has a closing pressure of 50 gr/cm2. Group 1 and 2 were subjected to the same type of injury at the end of 21 days. Four weeks later after trauma, both three groups were sacrificed and injured sciatic nerve sections are taken for histopathological analysis.
Results: It was observed that cotinine aggravated the traumatic degeneration and as privileged caused to fibrosis. In the Schwann cells of thick-myelinated fibers exhibited higher grades of degeneration and mitochondrial augmentation. According to the multiple comparison results, the number of Wallerian degenerations in the trauma group was significantly lower than in both the drug-control (p=0.016) and drug (p<0.001) groups. This situation was estimated as a response to oxidative stress.
Conclusion: This study reveals that peripheral nerve regeneration after traumatic injury may be affected negatively in smokers.
References
- Warren CW, Jones NR, Eriksen MP, Asma S. Patterns of global tobacco use in young people and implications for future chronic disease burden in adults. Lancet. 2006;367(9512):749-53.
- Benner CL, Bayona JM, Caka FM, Tang H, Lewis L, Crawford J, et al. Chemical composition of environmental tobacco smoke and two particulate-phase compounds. Environ Sci Technol. 1986;23(6):688-99.
- Kawachi I, Colditz GA. Invited commentary: confounding, measurement error, and publication bias in studies of passive smoking. Am J Epidemiol. 1996;144(10):909-15.
- Hegaard HK, Kjaergaard H, Møller LF, Wachmann H, Ottesen B. Determination of a saliva cotinine cut-off to distinguish pregnant smokers from pregnant non-smokers. Acta Obstet Gynecol Scand. 2007;86(4):401-6.
- DeLorenze GN, Kharrazi M, Kaufman FL, Eskenazi B, Bernert JT. Exposure to environmental tobacco smoke in pregnant women: the association between self-report and serum cotinine. Environ Res. 2002;90(1):21-32.
- Rodriguez-Fontan F, Reeves B, Tuaño K, Colakoglu S, D' Agostino L, Banegas R. Tobacco use and neurogenesis: A theoretical review of pathophysiological mechanism affecting the outcome of peripheral nerve regeneration. J Orthop. 2020;22:59-63.
- Benowitz NL, Jacob P 3rd, Fong I, Gupta S. Nicotine metabolic profile in man: comparison of cigarette smoking and transdermal nicotine. J Pharmacol Exp Ther. 1994;268(1):296-303.
- Benowitz NL, Jacob P 3rd. Metabolism of nicotine to cotinine studied by a dual stable isotope method. Clin Pharmacol Ther. 1994;56(5):483-93.
- Simske NM, Krebs JC, Heimke IM, Scarcella NR, Vallier HA. Nerve injury with acetabulum fractures: Incidence and factors affecting recovery. J Orthop Trauma. 2019;33(12):628-34.
- Ding ZM, Gao Y, Sentir AM, Tan X. Self-administration of cotinine in Wistar rats: Comparisons to nicotine. J Pharmacol Exp Ther. 2021;376(3):338-47.
- Lewis DF, Dickins M, Lake BG, Eddershaw PJ, Tarbit MH, Goldfarb PS. Molecular modelling of the human cytochrome P450 isoform CYP2A6 and investigations of CYP2A substrate selectivity. Toxicology. 1999;133(1):1-33.
- Visoni S, Meireles N, Monteiro L, Rossini A, Pinto LF. Different modes of inhibition of mouse Cyp2a5 and rat CYP2A3 by the food-derived 8-methoxypsoralen. Food Chem Toxicol. 2008;46(3):1190-5.
- Benowitz NL. Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiol Rev. 1996;18(2):188-204.
- Caldwell WS, Greene JM, Byrd GD, Chang KM, Uhrig MS, deBethizy JD, et al. Characterization of the glucuronide conjugate of cotinine: A previously unidentified major metabolite of nicotine in smokers’ urine. Chem Res Toxicol. 1992;5(2):280-5.
- Hammond SK, Leaderer BP. A diffusion monitor to measure exposure to passsive smoking. Environ Sci Technol. 1987;21(5):494-7.
- Nakajima M, Fukami T, Yamanaka H, Higashi E, Sakai H, Yoshida R, et al. Comprehensive evaluation of variability in nicotine metabolism and CYP2A6 polymorphic alleles in four ethnic populations. Clin Pharmacol Ther. 2006;80(3):282-97.
- Hukkanen J, Jacob P 3rd, Benowitz NL. Effect of grapefruit juice on cytochrome P450 2A6 and nicotine renal clearance. Clinical Pharmacol Ther. 2006;80(5):522-30.
- de Leon J, Diaz FJ, Rogers T, Browne D, Dinsmore L, Ghosheh OH, et al. Total cotinine in plasma: a stable biomarker for exposure to tobacco smoke. J Clin Psychopharmacol. 2002;22(5):496-501.
- Li Y, Bickel KD, Im MJ, Hu L, Dellon AL, Vander Kolk CA, et al. Effects of deferoxamine on ischemia/reperfusion injury after peripheral nerve compression. Ann Plast Surg. 1996;36(4):365-9.
- Macchi MM, Bruce JN. Human pineal physiology and functional significance of melatonin. Front Neuroendocrinol. 2004;25(3-4):177-95.
- Zhang YL, Zhang PB, Qiu SD, Liu Y, Tian YF, Wang Y. Effects of ketamine-midazolam anesthesia on the expression of NMDA and AMPA receptor subunit in the peri-infarction of rat brain. Chin Med J (Engl). 2006;119(18):1555-62.
- Túnez I, Montilla P, Muñoz MC, Drucker-Colín R. Effect of nicotine on 3 nitropropionic acid-induced oxidative stress in synaptosomes. Eur J Pharmacol. 2004;504(3):169-75.
- Paquette ST, Dawes RP, Sundar IK, Rahman I, Brown EB, White PM. Chronic cigarette smoke exposure drives spiral ganglion neuron loss in mice. Sci Rep. 2018;8(1):5746.
- Camp CL, Ryan CB, Degen RM, Dines JS, Altchek DW, Werner BC. Risk factors for revision surgery following isolated ulnar nerve release at the cubital tunnel: A study of 25,977 cases. J Shoulder Elbow Surg. 2017;26(4):710-5.
- Santiago HA, Zamarioli A, Sousa Neto MD, Volpon JB. Exposure to secondhand smoke impairs fracture healing in rats. Clin Orthop Relat Res. 2017;475(3):894-902.
- Andersen AM, Lei MK, Beach SRH, Philibert RA. Inflammatory biomarker relationships with helper T cell GPR15 expression and cannabis and tobacco smoking. J Psychosom Res. 2021;141:110326.
- Chen LE, Seaber AV, Glisson RR, Davies H, Murrell GA, Anthony DC, et al. The functional recovery of peripheral nerves following defıned acute crush injuries. J Orthop Res. 1992;10(5):657-64.
- Kasahara K, Nakagawa T, Kubota T. Neuronal loss and expression of neurotrophic factors in a model of rat chronic compressive spinal cord injury. Spine (Phila Pa 1976). 2006;31(18):2059-66.
- Boiangiu RS, Mihasan M, Gorgan DL, Stache BA, Hritcu L. Anxiolytic, promnesic, anti-acetylcholinesterase and antioxidant effects of Cotinine and 6-hydroxy-L-nicotine in scopolamine-induced zebrafish (Danio rerio) model of alzheimer's disease. Antioxidants (Basel). 2021;10(2):212.
- Sayan H, Ozacmak VH, Özen OA, Coskun O, Arslan SO, Sezen SC, et al. Benefıcial effects of melatonin on reperfusion injury in rat sciatic nerve. J Pineal Res. 2004;37(3):143-8.
- Cheeseman KH, Slater TF. An introduction to free radical biochemistry. Br Med Bull. 1993;49(3):481-43.