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  1. Hapidin H, Othman F, Soelaiman IN, Shuid AN, Luke DA, Mohamed N
    J. Bone Miner. Metab., 2007;25(2):93-8.
    PMID: 17323178
    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.
    Matched MeSH terms: Nicotine/pharmacology*
  2. Al-Obaidi MM, Al-Bayaty FH, Al Batran R, Ibrahim OE, Daher AM
    Curr Pharm Des, 2016;22(16):2403-10.
    PMID: 27139374
    OBJECTIVES: -To examine the effect of nicotine (Ni) on bone socket healing treated with Ellagic acid (EA) after tooth extraction in rat.

    MATERIALS AND METHODS: Thirty-Two Sprague Dawley (SD) male rats were divided into four groups. The group 1 was administrated with distilled water intragastrically and injected sterile saline subcutaneously. The group 2 was administrated with EA orally and injected with sterile saline subcutaneously. The groups 3 & 4 were subcutaneously exposed to Ni for 4 weeks twice daily before tooth extraction procedure, and maintained Ni injection until the animals were sacrificed. After one month Ni exposure, the group 4 was fed with EA while continuing Ni injection. All the groups were anesthetized, and the upper left incisor was extracted. Four rats from each group were sacrificed on 14(th) and 28(th) days. Tumour necrosis factor alpha (TNFα), Interleukin-1 beta (IL-1β) and Interleukin-6 (IL-6) were applied to assess in serum rat at 14th and 28(th) days. Superoxide dismutase (SOD) and Thiobarbituric acid reactive substances (TBRAS) levels were assessed to evaluate the antioxidant status and lipid peroxidation accordingly after tooth extraction in homogenized gingival maxilla tissue of rat at 14(th) and 28(th) days. The socket hard tissue was stained by eosin and hematoxylin (H&E); immunohistochemical technique was used to assess the healing process by Osteocalcin (OCN) and Alkaline Phosphatase (ALP) biomarkers.

    RESULTS: Ni-induced rats administered with EA compound (Group 4) dropped the elevated concentration of pro-inflammatory cytokines significantly when compared to Ni-induced rats (Group 3) (p<0.05). Ni-induced rats administrated with EA compound (Group 4) showed significant production of SOD and recession in TBRAS level when compared to Ni-induced rats (Group 3) (p<0.05). The immunohistochemistry analysis has revealed that OCN and ALP have presented stronger expression in Ni-induced rats treated with EA (Group 4), as against Ni-induced rats (Group 3).

    CONCLUSION: We have concluded that, Ni-induced rats, treated with EA have exerted positive effect on the trabecular bone formation after tooth extraction in nicotinic rats could be due to the antioxidant activity of EA which lead to upregulate of OCN and ALP proteins which are responsible for osteogenesis.

    Matched MeSH terms: Nicotine/pharmacology*
  3. Ammar Aldaddou W, Aljohani ASM, Adewale Ahmed I, Al-Wabel NA, El-Ashmawy IM
    Chem Biodivers, 2023 Jul;20(7):e202300115.
    PMID: 37236909 DOI: 10.1002/cbdv.202300115
    Most heavy metals and industrial chemicals such as nicotine and lead cause harm to the reproduction process through a decrease in sperm motility, fertilization process, and sperm binding to the oocyte. Salvia officinalis L. (sage) has been reported to enhance serum testosterone levels and other certain biochemical enzymes. Thus, the current study is aimed at evaluating the potential health benefits of S. officinalis L. methanol extract on lead and nicotine hydrogen tartrate-induced sperm quality degeneration in male rats and also identifying some of the non-polar volatile bioactive compounds that might be attributed to the bioactivity of S. officinalis extract using gas chromatography-mass spectrometry (GC/MS). In the study, fifty-four mature male albino rats of about 220-250 g [were divided randomly and equally into 9 groups (n=6)]. Sperm quality degeneration was induced through the oral administration of 1.5 g/L of lead acetate in drinking water or peritoneal injection of 0.50 mg/kg (animal weight) nicotine hydrogen tartrate for sixty days. Two doses (200 & 400 mg/kg b.w.) of S. officinalis L. were used. The rats were anesthetized after the experimental period and then sacrificed. Blood samples were collected while the epididymis, testicle, and accessory sex organs (prostates and seminal vesical) were taken for histopathological studies. Twelve major compounds were identified through the GC/MS analysis of S. officinalis L. methanol extract. Lead and nicotine toxicity had a great effect on the rats' sperm quality causing a significant (p<0.05) decrease in the quantity of sperm and sperm motility as well as an upsurge in the abnormalities of the sperm and a reduction in the length & diameter of seminiferous tubules and size & weight of sexual organs (accessory sex glands, epididymis, and testis). The administration of S. officinalis L. methanol extract, however, had a positive impact on the sexual organ weights, semen quality & quantity, and rats' fertility, thus, ameliorating the adversative effects of both lead and nicotine. Further evaluation and isolation of the bioactive components are recommended as potential drug leads.
    Matched MeSH terms: Nicotine/pharmacology
  4. 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/pharmacology*
  5. Abd Rashid N, Hapidin H, Abdullah H, Ismail Z, Long I
    Brain Behav, 2017 06;7(6):e00704.
    PMID: 28638710 DOI: 10.1002/brb3.704
    INTRODUCTION: REM sleep deprivation is associated with impairment in learning and memory, and nicotine treatment has been shown to attenuate this effect. Recent studies have demonstrated the importance of DREAM protein in learning and memory processes. This study investigates the association of DREAM protein in REM sleep-deprived rats hippocampus upon nicotine treatment.

    METHODS: Male Sprague Dawley rats were subjected to normal condition, REM sleep deprivation and control wide platform condition for 72 hr. During this procedure, saline or nicotine (1 mg/kg) was given subcutaneously twice a day. Then, Morris water maze (MWM) test was used to assess learning and memory performance of the rats. The rats were sacrificed and the brain was harvested for immunohistochemistry and Western blot analysis.

    RESULTS: MWM test found that REM sleep deprivation significantly impaired learning and memory performance without defect in locomotor function associated with a significant increase in hippocampus DREAM protein expression in CA1, CA2, CA3, and DG regions and the mean relative level of DREAM protein compared to other experimental groups. Treatment with acute nicotine significantly prevented these effects and decreased expression of DREAM protein in all the hippocampus regions but only slightly reduce the mean relative level of DREAM protein.

    CONCLUSION: This study suggests that changes in DREAM protein expression in CA1, CA2, CA3, and DG regions of rat's hippocampus and mean relative level of DREAM protein may involve in the mechanism of nicotine treatment-prevented REM sleep deprivation-induced learning and memory impairment in rats.

    Matched MeSH terms: Nicotine/pharmacology*
  6. Norazlina M, Lee PL, Lukman HI, Nazrun AS, Ima-Nirwana S
    Singapore Med J, 2007 Mar;48(3):195-9.
    PMID: 17342286
    Nicotine has been shown to exert negative effects on bone. This study determined whether vitamin E supplementation is able to repair the nicotine-induced adverse effects in bone.
    Matched MeSH terms: Nicotine/pharmacology*
  7. Kamsani YS, Rajikin MH, Mohamed Nor Khan NA, Abdul Satar N, Chatterjee A
    Med Sci Monit Basic Res, 2013 Mar 06;19:87-92.
    PMID: 23462735 DOI: 10.12659/MSMBR.883822
    BACKGROUND: This study aimed to evaluate the adverse effects of various doses of nicotine and protective effects of different concentrations of gamma-tocotrienol (gamma-TCT) on in vitro embryonic development and lipid peroxidation in mice.

    MATERIAL AND METHODS: A) Effects of various doses of nicotine on in vitro embryonic development: Female mice were treated with 1.0, 3.0, or 5.0 mg/kg/day nicotine for 7 consecutive days. Animals were superovulated, cohabited overnight, and sacrificed. Embryos were cultured in vitro. Plasma was assayed. B) Effects of concomitant treatment of nicotine concurrently with various doses of gamma-TCT on in vitro embryonic development: Female mice were treated with nicotine (5.0 mg/kg/day), gavaged gamma-TCT of 30, 60, or 90 mg/kg/day or nicotine concurrently with gamma-TCT of 3 different doses for 7 consecutive days. Animals were superovulated, cohabited overnight, and sacrificed. Embryos were cultured and plasma was assayed.

    RESULTS: A) Effects of various doses of nicotine on in vitro embryonic development: Number of hatched blastocysts decreased in 1.0 and 3.0 mg/kg/day nicotine groups. Nicotine at 5.0 mg/kg/day stopped embryo development at morula. MDA concentrations increased following all nicotine doses. B) Effects of concomitant treatment of nicotine concurrently with various doses of gamma-TCT on in vitro embryonic development: Embryo development was completed in all groups. MDA concentration increased only in the group treated with nicotine concurrently with 30 mg/kg/day gamma-TCT.

    CONCLUSIONS: Nicotine impairs in vitro embryo development and increases MDA in plasma. The deleterious impact of nicotine on embryo development is reversed by supplementing gamma-TCT concurrently with nicotine.

    Matched MeSH terms: Nicotine/pharmacology
  8. Chellian R, Pandy V, Mohamed Z
    Eur J Pharmacol, 2018 Jan 05;818:10-16.
    PMID: 29042206 DOI: 10.1016/j.ejphar.2017.10.025
    In the present study, the effect α-asarone on nicotine withdrawal-induced depression-like behavior in mice was investigated. In this study, mice were exposed to drinking water or nicotine solution (10-200µg/ml) as a source of drinking for forty days. During this period, daily fluid consumption, food intake and body weight were recorded. The serum cotinine level was estimated before nicotine withdrawal. Naïve mice or nicotine-withdrawn mice were treated with α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) for eight consecutive days and the forced swim test (FST) or locomotor activity test was conducted. In addition, the effect of α-asarone or bupropion on the hippocampal pCREB, CREB and BDNF levels during nicotine-withdrawal were measured. Results indicated that α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) pretreatment did not significantly alter the immobility time in the FST or spontaneous locomotor activity in naïve mice. However, the immobility time of nicotine-withdrawn mice was significantly attenuated with α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) pretreatment in the FST. Besides, α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) pretreatment significantly attenuated the hippocampal pCREB levels in nicotine-withdrawn mice. Overall, the present results indicate that α-asarone treatment attenuated the depression-like behavior through the modulation of hippocampal pCREB levels during nicotine-withdrawal in mice.
    Matched MeSH terms: Nicotine/pharmacology*
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