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Negative effects of nicotine on bone-resorbing cytokines and bone histomorphometric parameters in male rats

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Abstract

The effects of nicotine administration on bone-resorbing cytokines, cotinine, and bone histomorphometric parameters were studied in 21 Sprague–Dawley male rats. Rats aged 3 months and weighing 250–300 g were divided into three groups. Group 1 was the baseline control (BC), which was killed without treatment. The other two groups were the control group (C) and the nicotine-treated group (N). The N group was treated with nicotine 7 mg/kg body weight and the C group was treated with normal saline only. Treatment was given by intraperitoneal injection for 6 days/week for 4 months. The rats were injected intraperitoneally with calcein 20 mg/kg body weight at day 9 and day 2 before they were killed. ELISA test kits were used to measure the serum interleukin-1 (IL-1), interleukin-6 (IL-6), and cotinine (a metabolite of nicotine) levels at the beginning of the study and upon completion of the study. Histomorphometric analysis was done on the metaphyseal region of the trabecular bone of the left femur by using an image analyzer. Biochemical analysis revealed that nicotine treatment for 4 months significantly increased the serum IL-1, IL-6, and cotinine levels as compared to pretreatment levels. In addition, the serum cotinine level was significantly higher in the N group than in the C group after 4 months treatment. Histomorphometric analysis showed that nicotine significantly decreased the trabecular bone volume (BV/TV), trabecular thickness (Tb.Th), double-labeled surface (dLS/BS), mineralizing surface (MS/BS), mineral appositional rate (MAR), and bone formation rate (BFR/BS), while causing an increase in the single-labeled surface (sLS/BS), osteoclast surface (Oc.S/BS), and eroded surface (ES/BS) as compared to the BC and C groups. In conclusion, treatment with nicotine 7 mg/kg for 4 months was detrimental to bone by causing an increase in the bone resorbing cytokines and cotinine levels. Nicotine also exerted negative effects on the dynamic trabecular histomorphometric parameters.

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References

  1. WA Pryor DG Prier DF Church (1983) ArticleTitleElectron-spin resonance study of mainstream and sidestream cigarette smoke: nature of the free radicals in gas-phase and in cigarette tar Environ Health Perspect 47 345–355 Occurrence Handle6297881 Occurrence Handle1:CAS:528:DyaL3sXhvFehsr4%3D

    PubMed  CAS  Google Scholar 

  2. DF Church WA Pryor (1985) ArticleTitleFree-radical chemistry of cigarette smoke and its toxicological implications Environ Health Perspect 64 111–126 Occurrence Handle3007083 Occurrence Handle1:CAS:528:DyaL28Xht1ChtLg%3D

    PubMed  CAS  Google Scholar 

  3. WA Pryor K Stone (1993) ArticleTitleOxidants in cigarette smoke. Radicals, hydrogen peroxide, peroxynitrate, and peroxynitrite Ann NY Acad Sci 28 12–27 Occurrence Handle10.1111/j.1749-6632.1993.tb39148.x

    Article  Google Scholar 

  4. EL Wynder D Hoffmann (1979) ArticleTitleTobacco and health. A societal challenge N Engl J Med 300 894–903 Occurrence Handle370598 Occurrence Handle1:CAS:528:DyaE1MXktFClsb8%3D Occurrence Handle10.1056/NEJM197904193001605

    Article  PubMed  CAS  Google Scholar 

  5. NL Benowitz F Kuyt P Jacob SuffixIII (1982) ArticleTitleCircadian blood nicotine concentrations during cigarette smoking Clin Pharmaol Ther 32 758–764 Occurrence Handle1:STN:280:DyaL3s%2FltFyguw%3D%3D

    CAS  Google Scholar 

  6. NL Benowitz F Kuyt P Jacob SuffixIII RT Jones AL Osman (1983) ArticleTitleCotinine disposition and effects Clin Pharmacol Ther 34 604–611 Occurrence Handle6627820 Occurrence Handle1:CAS:528:DyaL2cXhvFWhug%3D%3D Occurrence Handle10.1038/clpt.1983.222

    Article  PubMed  CAS  Google Scholar 

  7. NL Benowitz P Jacob SuffixIII (1993) ArticleTitleNicotine and cotinine elimination pharmacokinetics in smokers and non-smokers Clin Pharmacol Ther 53 316–323 Occurrence Handle8453850 Occurrence Handle1:CAS:528:DyaK3sXitVOgtbk%3D Occurrence Handle10.1038/clpt.1993.27

    Article  PubMed  CAS  Google Scholar 

  8. NL Benowitz (1996) ArticleTitleCotinine as a biomarker of environmental tobacco smoke exposure Epidemiologic Rev 18 188–204 Occurrence Handle1:STN:280:DyaK2s7ntlCjtA%3D%3D

    CAS  Google Scholar 

  9. UE Ziegler J Kauczok UA Dietz HB Reith K Schmidt (2004) ArticleTitleClinical correlation between the consumption of nicotine and cotinine concentrations in urine and serum by competitive enzyme-linked immunosorbent assay Pharmacology 72 254–259 Occurrence Handle15539886 Occurrence Handle10.1159/000080381 Occurrence Handle1:CAS:528:DC%2BD2cXps1Ontbs%3D

    Article  PubMed  CAS  Google Scholar 

  10. GJ Wetscher M Bagchi D Bagchi G Perdikis PR Hinder K Glaser RA Hinder (1995) ArticleTitleFree radical production in nicotine treated pancreatic tissue Free Radic Biol Med 18 877–882 Occurrence Handle7797095 Occurrence Handle10.1016/0891-5849(94)00221-5 Occurrence Handle1:CAS:528:DyaK2MXkslSkurw%3D

    Article  PubMed  CAS  Google Scholar 

  11. C Kalpana VP Menon (2004) ArticleTitleProtective effect of circumin on circulatory lipid peroxidation and antioxidant status during nicotine-induced toxicity Toxicol Mech Methods 14 339–343 Occurrence Handle10.1080/15376520490434692 Occurrence Handle1:CAS:528:DC%2BD2cXpsF2qu7s%3D Occurrence Handle20021100

    Article  CAS  PubMed  Google Scholar 

  12. H Suleyman K Gumustekin S Taysi S Keles N Oztasan O Aktas K Altinkaynak H Timur F Akcay S Akar S Dane M Gul (2002) ArticleTitleBeneficial effects of Hippophae rhamnoides L. on nicotine induced oxidative stress in rat blood compared with vitamin E Biol Pharm Bull 25 1133–1136 Occurrence Handle12230103 Occurrence Handle10.1248/bpb.25.1133 Occurrence Handle1:CAS:528:DC%2BD38Xnt1entrc%3D

    Article  PubMed  CAS  Google Scholar 

  13. B Halliwell (1994) ArticleTitleFree radicals, antioxidants, and human disease: curiosity, cause, or consequence Lancet 10 721–724 Occurrence Handle10.1016/S0140-6736(94)92211-X

    Article  Google Scholar 

  14. IR Garrett BF Boyce ROC Oreffo L Bonewald J Poser GR Mundy (1990) ArticleTitleOxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo J Clin Invest 85 632–639 Occurrence Handle2312718 Occurrence Handle1:CAS:528:DyaK3cXhslaktrs%3D Occurrence Handle10.1172/JCI114485

    Article  PubMed  CAS  Google Scholar 

  15. N Suda I Morita T Kurodo S Murot (1993) ArticleTitleParticipitation of oxidative stress in the process of osteoclast differentiation Biochim Biophys Acta 1157 318–323 Occurrence Handle8323962 Occurrence Handle1:CAS:528:DyaK3sXmsVKltLw%3D

    PubMed  CAS  Google Scholar 

  16. N Mody F Parhami TA Sarafian DL Demer (2001) ArticleTitleOxidative stress modulates osteoblastic differentiation of vascular and bone cells Free Radic Biol Med 31 509–519 Occurrence Handle11498284 Occurrence Handle10.1016/S0891-5849(01)00610-4 Occurrence Handle1:CAS:528:DC%2BD3MXlslGnur4%3D

    Article  PubMed  CAS  Google Scholar 

  17. NS Ahmad BAK Khalid S Ima-Nirwana (2004) ArticleTitleEffects of vitamin E on interleukin-1 in ferric nitrilotriacetate treated rats Malays J Biochem Biol 9 43–47

    Google Scholar 

  18. NS Ahmad BAK Khalid DA Luke S Ima-Nirwana (2005) ArticleTitleTocotrienol offers better protection than tocotrienol from free radical-induced damage of rat bone Clin Exp Pharmacol Physiol 32 761–770 Occurrence Handle16173934 Occurrence Handle10.1111/j.1440-1681.2005.04264.x Occurrence Handle1:CAS:528:DC%2BD2MXhtVGgsr%2FK

    Article  PubMed  CAS  Google Scholar 

  19. SR Goldring MB Goldring (1996) ArticleTitleCytokines and skeletal physiology Clin Orthop 324 13–23 Occurrence Handle8595748 Occurrence Handle10.1097/00003086-199603000-00003

    Article  PubMed  Google Scholar 

  20. H Siggelkow T Eidner G Lehmann V Viereck D Raddatz U Munzel G Hein M Hufner (2003) ArticleTitleCytokines, osteoprotegerin, and RANKL in vitro and histomorphometric indices of bone turnover in patients with different bone diseases J Bone Miner Res 18 529–538 Occurrence Handle12619938 Occurrence Handle10.1359/jbmr.2003.18.3.529 Occurrence Handle1:CAS:528:DC%2BD3sXitVyrsb8%3D

    Article  PubMed  CAS  Google Scholar 

  21. A Grey MA Mitnick S Shapses A Ellison C Grunberg K Insogna (1996) ArticleTitleCirculating levels of interleukin-6 and tumor necrosis factor-alpha are elevated in primary hyperparathyroidism and correlate with markers of bone-resorption: a clinical research center study J Clin Endocrinol Metab 8 3450–3454 Occurrence Handle10.1210/jc.81.10.3450

    Article  Google Scholar 

  22. L Rifas (1999) ArticleTitleBone and cytokines: beyond IL-1, IL-6 and TNF-alpha Calcif Tissue Int 64 1–7 Occurrence Handle9868276 Occurrence Handle10.1007/s002239900570 Occurrence Handle1:CAS:528:DyaK1MXktVynsg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  23. PS Tappia KL Troughton SC Langley-Evans FR Grimble (1995) ArticleTitleCigarette smoking influences cytokine production and antioxidant defences Clin Sci (Lond) 88 485–489 Occurrence Handle1:STN:280:DyaK2MzgvVyqtA%3D%3D

    CAS  Google Scholar 

  24. AR Kamer N El-Ghorab N Marzec JE Margarone Suffix3rd R Dziak (2006) ArticleTitleNicotine induced proliferation and cytokine release in osteoblastic cells Int. J Mol Med 17 121–127 Occurrence Handle16328020 Occurrence Handle1:CAS:528:DC%2BD28Xntlaisg%3D%3D

    PubMed  CAS  Google Scholar 

  25. JE Compston PI Croucher (1991) ArticleTitleHistomorphometric analysis of trabecular bone remodelling in osteoporosis Bone Miner 14 91–102 Occurrence Handle1912765 Occurrence Handle10.1016/0169-6009(91)90086-F Occurrence Handle1:STN:280:DyaK38%2FgsVajsA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  26. J Difford (1974) ArticleTitleA simplified method for the preparation of methyl methacrylate embedding medium Med Lab Tech 31 79–81 Occurrence Handle1:STN:280:DyaE2M%2FotFyqtQ%3D%3D

    CAS  Google Scholar 

  27. ER Weibel GS Kistler WF Scherle (1966) ArticleTitlePractical stereological methods for morphometric cytology J Cell Biol 30 23–38 Occurrence Handle5338131 Occurrence Handle10.1083/jcb.30.1.23 Occurrence Handle1:STN:280:DyaF2s7msFersg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  28. RH Freere ER Weibel (1967) ArticleTitleStereologic techniques in microscopy J R Microsc Soc 87 25–34

    Google Scholar 

  29. PA Baldock HA Morris AG Need RJ Moore TC Durbridge (1998) ArticleTitleVariation in the short-term changes in bone cell activity in three regions of the distal femur immediately following ovariectomy J Bone Miner Res 13 1451–1457 Occurrence Handle9738518 Occurrence Handle10.1359/jbmr.1998.13.9.1451 Occurrence Handle1:STN:280:DyaK1cvgvVyqug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  30. AM Parfitt MK Drezner FH Glorieux JA Kanis H Malluche PJ Meunier SM Ott RR Recker (1987) ArticleTitleBone histomorphometry: standardization of nomenclature, symbols and units. Report of the ASMBR histomorphometry nomenclature committee J Bone Miner Res 2 595–610 Occurrence Handle3455637 Occurrence Handle1:STN:280:DyaL1czjvVemsQ%3D%3D Occurrence Handle10.1002/jbmr.5650020617

    Article  PubMed  CAS  Google Scholar 

  31. TJ Wronski LM Dann KS Scott M Cintron (1989) ArticleTitleLong-term effects of ovariectomy and aging on the rat skeleton Calcif Tissue Int 45 360–366 Occurrence Handle2509027 Occurrence Handle10.1007/BF02556007 Occurrence Handle1:STN:280:DyaK3c%2FivFKkug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  32. M Norazlina YMK Nik-Farideh A Arizi A Faisal S Ima-Nirwana (2004) ArticleTitleEffects of nicotine on bone resorbing cytokines in male rats Int Med J 3 IssueID2 1–9

    Google Scholar 

  33. R Soto-Otero E Mendez-Alvarez A Hermida-Ameijeiras AM Lopez-Real JL Labandeira-Garcia (2002) ArticleTitleEffects of (−)-nicotine and (−)-cotinine on 6-hydroxydopamine-induced oxidative stress and neurotoxicity: relevance for Parkinson's disease Biochem Pharmacol 64 125–135 Occurrence Handle12106613 Occurrence Handle10.1016/S0006-2952(02)01070-5 Occurrence Handle1:CAS:528:DC%2BD38XltFSqsL8%3D

    Article  PubMed  CAS  Google Scholar 

  34. S Ima-Nirwana CT Cheng M Norazlina (2005) ArticleTitleEffects of nicotine on bone mineral density and calcium homeostasis in male Sprague–Dawley rats Curr Topic Pharmacol 9 125–129 Occurrence Handle1:CAS:528:DC%2BD2sXjs1Wmsrg%3D

    CAS  Google Scholar 

  35. PR Nelson JD deBethizy RA Davis GB Oldaker SuffixIII (1991) Where there's smoke …? Biases in the use of nicotine and cotinine as environmental tobacco smoke biomarker Proceedings of the 1991 Environmental Protection Agency/Air and Waste Management Association International Symposium: Measurement of Toxic Related Air Pollutants Air and Waste Management Association Pittsburgh, PA 449–454

    Google Scholar 

  36. L Nguyen FE Dewhirst PV Hauschka P Stashenko (1991) ArticleTitleInterleukin-1 beta stimulates bone resorption and inhibits bone formation in vivo Lymphokine Cytokine Res 10 15–21 Occurrence Handle1873357 Occurrence Handle1:CAS:528:DyaK3MXksVOmsLk%3D

    PubMed  CAS  Google Scholar 

  37. CL Henemyre DK Scales SD Hokett MF Cuenin ME Peacock MH Parker PD Brewer AH Chuang (2003) ArticleTitleNicotine stimulates osteoclast resorption in a porcine marrow cell model J Periodontol 74 1440–1446 Occurrence Handle14653389 Occurrence Handle10.1902/jop.2003.74.10.1440 Occurrence Handle1:CAS:528:DC%2BD3sXpvVOnu7Y%3D

    Article  PubMed  CAS  Google Scholar 

  38. LL Key WL Ries RG Taylor BD Hays BL Pitzer (1990) ArticleTitleOxygen derived free radicals in osteoclasts: the location and specificity of nitroblue tetrazolium reaction Bone (NY) 11 115–119 Occurrence Handle1:CAS:528:DyaK3MXhs1WgtL0%3D

    CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Anatomy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia

    Hermizi Hapidin & Faizah Othman

  2. Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia

    Ima-Nirwana Soelaiman, Ahmad N. Shuid & Norazlina Mohamed

  3. Department of Clinical Oral Biology, Faculty of Dentistry, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia

    Douglas A. Luke

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  1. Hermizi Hapidin
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Correspondence to Norazlina Mohamed.

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Hapidin, H., Othman, F., Soelaiman, IN. et al. Negative effects of nicotine on bone-resorbing cytokines and bone histomorphometric parameters in male rats. J Bone Miner Metab 25, 93–98 (2007). https://doi.org/10.1007/s00774-006-0733-9

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  • DOI: https://doi.org/10.1007/s00774-006-0733-9

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