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The Role of Dietary Compounds in the Therapy of Nicotine-Induced Osteoporosis

Mohamed N, Muhammad N, Shuid AN, Soelaiman IN

Curr Drug Targets, 2018;19(12):1424-1430.
PMID: 28950810 DOI: 10.2174/1389450118666170925154428

Nicotine is one of the most abused substances worldwide and can cause several harmful effects on health. One of the harmful effects, which is often ignored, is osteoporosis. Smoking has been shown to cause a decrease in bone mineral density in humans. Animal studies have proven that nicotine exerts negative effects on bone. The number of people who smoke increases each day. Those who smoke start at a very young age and they usually smoke for years. This will increase the risk of developing osteoporosis. As the prevalence of osteoporosis increases, the risk of fractures also increases. The major concerns are disability following fractures, mortality due to complications after fractures and the increasing cost of management and therapy. This paper will review the effects of nicotine on bone and the potential natural products which can be used as treatment for nicotine-induced osteoporosis.

Matched MeSH terms: Nicotine/adverse effects*
Fulltext Dietary spices protect against hydrogen peroxide-induced DNA damage and inhibit nicotine-induced cancer cell migration

Jayakumar R, Kanthimathi MS

Food Chem, 2012 Oct 01;134(3):1580-4.
PMID: 25005983 DOI: 10.1016/j.foodchem.2012.03.101

Spices are rich sources of antioxidants due to the presence of phenols and flavonoids. In this study, the DNA protecting activity and inhibition of nicotine-induced cancer cell migration of 9 spices were analysed. Murine fibroblasts (3T3-L1) and human breast cancer (MCF-7) cells were pre-treated with spice extracts and then exposed to H₂O₂ and nicotine. The comet assay was used to analyse the DNA damage. Among the 9 spices, ginger, at 50 μg/ml protected against 68% of DNA damage in 3T3-L1 cells. Caraway, cumin and fennel showed statistically significant (p<0.05) DNA protecting activity. Treatment of MCF-7 cells with nicotine induced cell migration, whereas pre-treatment with spices reduced this migration. Pepper, long pepper and ginger exhibited a high rate of inhibition of cell migration. The results of this study prove that spices protect DNA and inhibit cancer cell migration.

Matched MeSH terms: Nicotine/adverse effects*
Fulltext Measurement of nicotine withdrawal symptoms: linguistic validation of the Wisconsin Smoking Withdrawal Scale (WSWS) in Malay

Awaisu A, Samsudin S, Amir NA, Omar CG, Hashim MI, Mohamad MH, et al.

BMC Med Res Methodol, 2010;10:46.
PMID: 20492717 DOI: 10.1186/1471-2288-10-46

The purpose of the linguistic validation of the Wisconsin Smoking Withdrawal Scale (WSWS) was to produce a translated version in Malay language which was "conceptually equivalent" to the original U.S. English version for use in clinical practice and research.

Matched MeSH terms: Nicotine/adverse effects
Fulltext Malaysian and Thai smokers' beliefs about the harmfulness of 'light' and menthol cigarettes

King B, Yong HH, Borland R, Omar M, Ahmad AA, Sirirassamee B, et al.

Tob Control, 2010 Dec;19(6):444-50.
PMID: 20852322 DOI: 10.1136/tc.2009.034256

This study explored the extent to which Malaysian and Thai smokers believe "light" and menthol cigarettes are less harmful than "regular" cigarettes and the correlates of these beliefs.

Matched MeSH terms: Nicotine/adverse effects*
Fulltext Resveratrol Supplementation Protects Against Nicotine-Induced Kidney Injury

Ramalingam A, Santhanathas T, Shaukat Ali S, Zainalabidin S

Int J Environ Res Public Health, 2019 11 12;16(22).
PMID: 31726798 DOI: 10.3390/ijerph16224445

Prolonged exposure to nicotine accelerates onset and progression of renal diseases in habitual cigarette smokers. Exposure to nicotine, either via active or passive smoking is strongly shown to enhance renal oxidative stress and augment kidney failure in various animal models. In this study, we investigated the effects of resveratrol supplementation on nicotine-induced kidney injury and oxidative stress in a rat model. Male Sprague-Dawley rats were given nicotine (0.6 mg/kg, i.p.) alone or in combination with either resveratrol (8 mg/kg, i.p.), or angiotensin II type I receptor blocker, irbesartan (10 mg/kg, p.o.) for 28 days. Upon completion of treatment, kidneys were investigated for changes in structure, kidney injury markers and oxidative stress. Administration of nicotine alone for 28 days resulted in significant renal impairment as shown by marked increase in plasma creatinine, blood urea nitrogen (BUN) and oxidative stress. Co-administration with resveratrol however successfully attenuated these changes, with a concomitant increase in renal antioxidants such as glutathione similar to the conventionally used angiotensin II receptor blocker, irbesartan. These data altogether suggest that targeting renal oxidative stress with resveratrol could alleviate nicotine-induced renal injury. Antioxidants may be clinically important for management of renal function in habitual smokers.

Matched MeSH terms: Nicotine/adverse effects*
Leptin and calorie intake among different nicotine dependent groups

Suhaimi MZ, Sanip Z, Jan HJ, Yusoff HM

Ann Saudi Med, 2016;36(6):404-408.
PMID: 27920412

BACKGROUND: Exposure to nicotine via tobacco smoking may influence leptin release and decrease food intake among smokers. However, the effect of nicotine exposure on leptin and food intake among different nicotine dependent groups is unclear.
OBJECTIVE: We aimed to measure leptin and calorie intake among different nicotine dependent groups.
DESIGN: Cross-sectional study.
SETTING: Research department in school of medical sciences.
PATIENTS AND METHODS: Subjects were selected by purposive (non-probability) sampling and categorized as having low, moderate and high nicotine dependency based on the Fagerstrom Test for Nicotine Dependence (FTND) score. Diet was recorded by interview. Anthropometry, blood pressure, body composition, lipid profile, and physical activity level were measured accordingly. Fasting serum leptin was measured using a commercial ELISA kit.
MAIN OUTCOME MEASURE(S): Nicotine dependency, 24-hour diet, clinical anthropometric and clinical measurements.
RESULTS: In 107 Malay male smokers leptin concentration was inversely correlated with nicotine dependence. However, body weight, smoking period, blood pressure, body composition, lipid profile and physical activity level were not significantly different among low, moderately and highly dependent smoking groups. Leptin concentration and total calorie intake were also not significantly different among these groups.
CONCLUSION: Leptin concentration was inversely correlated with nicotine dependence, but leptin concentration and total calorie intake status were not significantly different among our different nicotine dependency subjects.
LIMITATIONS: Purposive sampling for subject recruitment and inaccurate information in the self-administered questionnaire.

Matched MeSH terms: Nicotine/adverse effects*
Effects of nicotine administration and nicotine cessation on bone histomorphometry and bone biomarkers in Sprague-Dawley male rats

Hapidin H, Othman F, Soelaiman IN, Shuid AN, Mohamed N

Calcif. Tissue Int., 2011 Jan;88(1):41-7.
PMID: 20953592 DOI: 10.1007/s00223-010-9426-4

Nicotine is a major alkaloid of tobacco, which can increase free radical formation, leading to osteoporosis. The effects of nicotine administration and cessation on bone histomorphometry and biomarkers were studied in 28 Sprague-Dawley male rats. Rats aged 3 months and weighing 250-300 g were divided into four groups: control (C, normal saline for 4 months), nicotine for 2 months (N2), nicotine for 4 months (N4), and nicotine cessation (NC). The NC group was given nicotine for the first 2 months and then allowed to recover for the following 2 months without nicotine. Histomorphometric analysis was done using an image analyzer. ELISA kits were used to measure serum osteocalcin (bone formation marker) and pyridinoline (PYD, bone resorption marker) levels at month 0, month 2, and month 4. All test groups showed a significant decrease in BV/TV, Ob.S/BS, dLS/BS, MAR, BFR/BS, and osteocalcin levels and an increase in sLS/BS and PYD levels compared to group C. No significant differences were observed in all parameters measured among the test groups, except for MAR and BFR/BS. In conclusion, nicotine administration at a dose of 7 mg/kg for 2 and 4 months has detrimental effects on bone metabolism. Nicotine administration at 7 mg/kg for 2 months is sufficient to produce significant effects on bone histomorphometric parameters and biomarkers. In addition, prolonging the treatment for another 2 months did not show any significant differences. Cessation of nicotine for 2 months did not reverse the effects.

Matched MeSH terms: Nicotine/adverse effects
Beneficial effects of tocotrienol and tocopherol on bone histomorphometric parameters in sprague-dawley male rats after nicotine cessation

Hermizi H, Faizah O, Ima-Nirwana S, Ahmad Nazrun S, Norazlina M

Calcif. Tissue Int., 2009 Jan;84(1):65-74.
PMID: 19020790 DOI: 10.1007/s00223-008-9190-x

This study was conducted to determine the effectiveness of three forms of vitamin E supplements following nicotine treatment on bone histomorphometric parameters in an adult male rat model. Rats were divided into seven groups: baseline (B, killed without treatment), control (C, normal saline for 4 months), nicotine (N, nicotine for 2 months), nicotine cessation (NC), tocotrienol-enhanced fraction (TEF), gamma-tocotrienol (GTT), and alpha-tocopherol (ATF). Treatments for the NC, TEF, GTT, and ATF groups were performed in two phases. For the first 2 months they were given nicotine (7 mg/kg), and for the following 2 months nicotine administration was stopped and treatments with respective vitamin E preparations (60 mg/kg) were commenced except for the NC group, which was allowed to recover without treatment. Rats in the N and NC groups had lower trabecular bone volume, mineral appositional rate (MAR), and bone formation rate (BFR/BS) and higher single labeled surface and osteoclast surface compared to the C group. Vitamin E treatment reversed these nicotine effects. Both the TEF and GTT groups, but not the ATF group, had a significantly higher trabecular thickness but lower eroded surface (ES/BS) than the C group. The tocotrienol-treated groups had lower ES/BS than the ATF group. The GTT group showed a significantly higher MAR and BFR/BS than the TEF and ATF groups. In conclusion, nicotine induced significant bone loss, while vitamin E supplements not only reversed the effects but also stimulated bone formation significantly above baseline values. Tocotrienol was shown to be slightly superior compared to tocopherol. Thus, vitamin E, especially GTT, may have therapeutic potential to repair bone damage caused by chronic smoking.

Matched MeSH terms: Nicotine/adverse effects
Roselle supplementation prevents nicotine-induced vascular endothelial dysfunction and remodelling in rats

Si LY, Kamisah Y, Ramalingam A, Lim YC, Budin SB, Zainalabidin S

Appl Physiol Nutr Metab, 2017 Jul;42(7):765-772.
PMID: 28249121 DOI: 10.1139/apnm-2016-0506

Vascular endothelial dysfunction (VED) plays an important role in the initiation of cardiovascular diseases. Roselle, enriched with antioxidants, demonstrates high potential in alleviating hypertension. This study was undertaken to investigate the effects of roselle supplementation of VED and remodelling in a rodent model with prolonged nicotine administration. Male Sprague-Dawley rats (n = 6 per group) were administered with 0.6 mg/kg nicotine for 28 days to induce VED. The rats were given either aqueous roselle (100 mg/kg) or normal saline orally 30 min prior to nicotine injection daily. One additional group of rats served as control. Thoracic aorta was isolated from rats to measure vascular reactivity, vascular remodelling and oxidative stress. Roselle significantly lowered aortic sensitivity to phenylephrine-induced vasoconstriction (Endo-(+) Cmax = 234.5 ± 3.9%, Endo-(-) Cmax = 247.6 ± 5.2%) compared with untreated nicotine group (Endo-(+) Cmax = 264.5 ± 6.9%, Endo-(-) Cmax = 276.5 ± 6.8%). Roselle also improved aortic response to endothelium-dependent vasodilator, acetylcholine (Endo-(+) Rmax = 73.2 ± 2.1%, Endo-(-) Rmax = 26.2 ± 0.8%) compared to nicotine group (Endo-(+) Rmax = 57.8 ± 1.7%, Endo-(-) Rmax = 20.9 ± 0.8%). In addition, roselle prevented an increase in intimal media thickness and elastic lamellae proliferation to preserve vascular architecture. Moreover, we also observed a significantly lowered degree of oxidative stress in parallel with increased antioxidant enzymes in aortic tissues of the roselle-treated group. This study demonstrated that roselle prevents VED and remodelling, and as such it has high nutraceutical value as supplement to prevent cardiovascular diseases.

Matched MeSH terms: Nicotine/adverse effects*