Effect of green tea and nicotine on haematological and biochemical parameters and histopathology of bone marrow and spleen on albino rats.

We investigate the effects of green tea extract (GTE) on the attenuation of nicotine hematotoxicity, oxidative stress, inflammation and spleen and bone marrow structural lesions. Rats were treated by injecting nicotine (1,5mg/kg b.w. for 7 weeks) intraperitoneally and thereby supplementing GTE 2% orally to them. Haematological profiles, inflammation markers, neutrophil/lymphocyte (NLR), platelet/lymphocyte (PLR) and mean platelet volume (MPV/Plat) ratios- and erythrocyte sedimentation rate (ESR) were evaluated. Splenic levels of malondialdehyde (MDA), nitric oxide (NO), advanced protein oxidation products (AOPP) and catalase activity were measured. Femur bone and spleen were subjected to histological study. Nicotine-induced haematological abnormalities, a rise in the NLR and MPV/Plat ratios and ESR values with a drop in the PLR values compared to other experimental groups and leads to a significant increase in MDA, NO and AOPP levels-with a decrease in catalase activity compared to control groups. The bone marrow and spleen of nicotine exposed rats showed severe degenerative changes. GTE supplementation attenuates hematotoxicity, induce a decrease in the inflammation markers values, improved the levels of MDA, NO, AOPP and catalase activity and attenuate the adverse histological effects. GTE rich on polyphenols and flavonoids revealed by the in vitro study protects against the hazardous effects of nicotine.

Ameliorative effect of methanolic extract of Tribulus terrestris L. on nicotine and lead-induced degeneration of sperm quality in male rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The use of herbal and medicinal plants to treat male infertility is well known in history. Tribulus terrestris L. (TT) belongs to the Zygophyllaceae family and it is used in folk medicine to vitalize and also improve both physical performance and sexual function in men in addition to the protective effect of the gross saponins of TT against ischemic stroke and its clinical anti-inflammatory property. AIM OF THE STUDY: This study aimed to investigate the effects of methanol extract of T. terrestris on nicotine hydrogen tartrate and lead-induced degeneration of sperm quality in male rats and to identify the volatile bioactive non-polar compounds thought to be responsible for its activity using gas chromatography-mass spectrometry (GC-MS). MATERIALS AND METHODS: The effect of T. terrestris on nicotine hydrogen tartrate and lead-induced infertility was evaluated in male rats. Fifty-four mature male albino rats weighing 220-250 g body weight were used. The rats were randomly divided into 9 equal groups (n = 6). Infertility was induced by administering nicotine hydrogen tartrate (0.50 mg/kg) through peritoneal injection (i.p.) or lead acetate (1.5 g/L) orally with drinking water for sixty days. Two doses (50 and 100 mg/kg body weight of the animal) of T. terrestris were also used. At the end of the experimental period, the rats were anesthetized and sacrificed. Blood samples were collected. Hormonal analyses were carried out on the serum. The testicle, epididymis, and accessory sex organs (seminal vesical and prostates) were removed for histopathological analysis. Gas chromatography-mass spectrometry (GC-MS) analysis of the methanol extract was also carried out to identify major volatile compounds in T. terrestris methanol extract. RESULTS: Nicotine and lead toxicity caused a significant (p < 0.05) decrease in the number of sperm, motility, and an increase in the sperm abnormalities such as the reduction in weight and size of sexual organs (testis, epididymis, and accessory sex glands), reduction of diameter and length of seminiferous tubules. The administration of T. terrestris methanol extract, however, improved the semen quantity and quality, sexual organ weights, and fertility of male rats and, thus, ameliorated the adverse effects of nicotine and lead. Ten major compounds were found from the GC-MS analysis of the extract of T. terrestris methanol extract. CONCLUSION: Findings showed that T. terrestris plant methanolic extracts ameliorated nicotine hydrogen tartrate and lead-induced degeneration of sperm quality in male rats. The GC-MS analysis of the T. terrestris plant methanolic extracts revealed the presence of several important bioactive compounds which were thought to be responsible for the ameliorative effect. Further isolation and evaluation of the individual components would provide relevant lead to finding new drugs.

The effect of toxic pyridine-alkaloid secondary metabolites on the sunbird gut microbiome.

Sunbirds feed on tobacco tree nectar which contains toxic nicotine and anabasine secondary metabolites. Our aim was to understand the effect of nicotine and anabasine on the gut microbiota composition of sunbirds. Sixteen captive sunbirds were randomly assigned to two diets: artificial nectar either with (treatment) or without (control) added nicotine and anabasine. Excreta were collected at 0, 2, 4 and 7 weeks of treatment and samples were processed for bacterial culture and high-throughput amplicon sequencing of the 16S rRNA gene. The gut microbiome diversity of the treated and control birds changed differently along the seven-week experiment. While the diversity decreased in the control group along the first three samplings (0, 2 and 4 weeks), it increased in the treatment group. The microbiota composition analyses demonstrated that a diet with nicotine and anabasine, significantly changed the birds' gut microbiota composition compared to the control birds. The abundance of nicotine- and anabasine- degrading bacteria in the excreta of the treated birds, was significantly higher after four and seven weeks compared to the control group. Furthermore, analysis of culturable isolates, including Lactococcus, showed that sunbirds' gut-associated bacteria were capable of degrading nicotine and anabasine, consistent with their hypothesised role as detoxifying and nutritional symbionts.

Effects of a dammarane-type saponin, ginsenoside Rd, in nicotine-induced vascular endothelial injury.

BACKGROUND: Panax notoginseng (Burk.) F.H. Chen is a traditional medicinal plant widely used to prevent and treat cardiovascular diseases. Ginsenoside Rd (GRd) is a major bioactive component of P. notoginseng, but specific effects on cardiovascular disease-related pathogenic processes are rarely studied, especially vascular endothelial injury. PURPOSE: This study investigated the potential protective efficacy of GRd against nicotine-induced vascular endothelial cell injury, disruption of vascular nitric oxide (NO) signaling, aberrant endothelium-monocyte adhesion, platelet aggregation, and vasoconstriction. STUDY DESIGN/METHODS: Vascular endothelial injury and functional disruption were investigated in cultured human umbilical vein endothelial cells (HUVECs) by biochemical assays for nitric oxide (NO) and angiotensin II (Ang II), immunofluorescence (IF) and western blotting for expression analyses of apoptosis- related proteins, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), Ang II type receptor 1 (AGTR1), toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B (NF-κB). In addition, vascular protection by GRd was examined in nicotine-administered Sprague-Dawley (SD) rats by serum NO and Ang II assays, and by hematoxylin-eosin (HE) and immunostaining of aorta. We also examined effects of GRd on monocyte (THP-1 cells) adhesion assays, adenosine diphosphate (ADP)-induced platelet aggregation, and phenylephrine (PE)-induced vasoconstriction of isolated rat aortic rings. RESULTS: In HUVECs, nicotine significantly suppressed NO production, enhanced Ang II production, downregulated eNOS expression, and upregulated expression levels of AGTR1, TLR4, MyD88, NF-κB, iNOS, Bax/Bcl-2 ratio, cleaved caspase-3, and cytochrome c (cyt c). All of these changes were significantly reversed by GRd. In rats, oral GRd reversed the reduction NO and enhanced Ang II production in serum induced by nicotine administration, and HE staining revealed protection of aortic endothelial cells. In addition, GRd reversed nicotine-mediated enhancement of HUVECs-monocyte adhesion, inhibited ADP-induced platelet aggregation and PE-induced vasoconstriction. CONCLUSION: GRd may prevent nicotine-induced cardiovascular diseases by preserving normal vascular endothelial NO signaling, suppressing platelet aggregation and vasoconstriction, and by preventing endothelial cell-monocyte adhesion.

Ameliorative Effects of Hydromethanolic Extract of Citrullus lanatus (Watermelon) Rind on Semen Parameters, Reproductive Hormones and Testicular Oxidative Status Following Nicotine Administration in Male Wistar Rats.

The present study examines the possible ameliorative effects of the hydromethanolic extract of Citrullus lanatus rind (HECL) on some reproductive function and oxidative indices of the testes in male Wistar rats following administration of nicotine. Twenty male rats were assigned into four groups: Group A to D of five rats each. Group A served as control and received 2ml/kg body weight of 10% extract vehicle; Group B received 1mg/kg body weight of nicotine; Group C were co-administered 1mg/kg body weight nicotine and 500 mg/kg body weight of HECL and Group D received only 500mg/kg body weight of HECL. The drugs and extracts were administered orally to the rats for 42days; blood samples were collected by direct cardiac puncture for determination of serum concentrations of testosterone, Follicle Stimulating Hormone and Luteinizing Hormone. The testes were also harvested for determination of semen parameters: motility, morphology, viability and count and testicular tissue processed for superoxide dismutase and malondialdehyde concentration. Compared to Group A control rats, administration of HECL significantly increased sperm count and reproductive hormone concentrations amongst Group B rats (p<0.05). Treatment with nicotine caused a significant reduction in the levels of all reproductive hormones with significant diminution of some sperm parameters: motility, morphology and viability; and decrease in superoxide dismutase and increase in malondialdehyde concentration amongst Group B rats compared to Group A control rats (p<0.05). Co-administration of HECL with nicotine to Group C rats apparently reversed the effects of nicotine resulting in significant increases in sperm count and the reproductive hormones concentration as compared to Group A control rats (p<0.05). Amongst Group D rats, the extract also caused a significant increase in superoxide dismutase concentration and a significant decrease in malondialdehyde concentration compared with the Group A control rats (p<0.05). The findings suggest that the hydromethanolic extract of Citrullus lanatus rind possibly ameliorates the deleterious effects of nicotine on some reproductive indices in male Wistar rats.

[Effect of electroacupuncture at "Zusanli" (ST 36) and "Yanglingquan" (GB 34) on perinatal nicotine-exposure-induced lung function and morphology of neonatal rats].

OBJECTIVE: To compare the effects of electroacupuncture (EA) at "Zusanli" (ST 36) versus "Yanglingquan" (GB 34) in the pregnant rats on perinatal nicotine-exposure-induced lung function and morphology of newborn rats and explore the rule of acupoint effect in EA for the prevention from lung dysplasia in newborn rats. METHODS: A total of 24 female SD rats were randomized into a normal saline group (S group), a nicotine group (N group), a nicotine-ST 36 group (N + ST 36 group) and a nicotine-GB 34 group (N+GB 34 group), 6 rats in each one. Starting at the 6th day of pregnancy, 0.9% sodium chloride solution was injected subcutaneously in the S group, 1 mg/kg; and in the rest 3 groups, nicotine of the same dose was injected through to the 21st postnatal day to establish the perinatal nicotine-exposure model. Simultaneously, during model preparation, EA was applied at "Zusanli" (ST 36) and "Yanglingquan" (GB 34) in the N+ST 36 group and the N+GB 34 group respectively, once a day, through to the 21st postnatal day. The lung function analytic system for small animal was adopted to observe the changes in lung function indicators in newborn rats, such as peak inspiratory flow (PIF), peak expiratory flow (PEF), expiratory resistance (RE), inspiratory resistance (RI) and dynamic compliance (Cdyn). HE staining was used to observe the morphological changes of lung, such as alveolar fusion and rupture. RESULTS: Compared with the S group, PEF and Cdyn were lower and PIF, RI and RE higher in the N group (all P<0.01), additionally, alveoli were fused and ruptured, alveolar wall thickened, the numbers of alveoli reduced, the interspace of alveoli enlarged and the diameter increased (P<0.01). Compared with the N group, in the N+ST 36 group, PEF and Cdyn were increased, PIF, RI and RE reduced (P<0.05, P<0.01), the alveolar fusion and rupture relieved, the numbers of alveoli increased, alveolar wall thinner, the interpsace of alveoli became normal and the diameter was reduced significantly (P<0.01). In the N+GB 34 group, the changes of lung function and morphological indicators were not significant (P>0.05). CONCLUSION: Electroacupuncture at "Zusanli" (ST 36) in the pregnant rats significantly improves the perinatal nicotine-exposure-induced lung function and morphology of newborn rats than electroacupuncture at "Yanglingquan" (GB 34).

Nephroprotective and antioxidant effect of green tea (Camellia sinensis) against nicotine-induced nephrotoxicity in rats and characterization of its bioactive compounds by HPLC-DAD.

Nicotine is a potential inducer of oxidative stress, through which it can damage numerous biological molecules. Natural antioxidants that prevent or slow the progression and severity of nicotine toxicity may have a significant health impact. The purpose of this study, conducted on Wistar rats, was to evaluate the beneficial effects of green tea (Camellia sinensis) extract on nicotine treatment-induced damage on kidney. Our results showed that nicotine significantly (p < 0.01) increased serum and kidney malondialdehyde, the serum contents of urea, creatinine, and uric acid. In addition, nicotine intoxication significantly (p < 0.01) decreased the levels of vitamins E and C in serum and kidney tissue as well as the activities of superoxide dismutase, catalase, and glutathione peroxidase. Interestingly, animals that were pretreated with green tea, prior to nicotine administration, showed a significant nephroprotection, revealed by a significant reduction-induced oxidative damage for all tested markers. The nephroprotective activity of green tea is mediated, at least in part, by the antioxidant effect of its constituents.

Evaluation of antioxidant and anti-lipid peroxidation potentials of Nigella sativa and onion extract on nicotine-induced lung damage.

BACKGROUND: The present work aimed to compare the protective effect of Nigella sativa (NS) and onion extract on the nicotine-induced lung damage in rats. The antioxidant and anti-lipid peroxidation potentials of both agents on nicotine-induced lung damage were studied. MATERIALS AND METHODS: Thirty-six Sprague-Dawley albino rats, treated for 18 weeks, were divided into six groups: one negative control group, two positive control groups (oral onion and oral NS), nicotine-treated group, onion extract-treated group (concomitant nicotine and onion extract) and NS-treated group (concomitant nicotine and NS oil). The assessment of lung structure was based on haematoxylin and eosin and transmission electron microscopy. Lung malondialdehyde (MDA), superoxide dismutase activity (SOD), catalase (CAT), lung glutathione (GSH), and epithelial lining fluid GSH (ELF GSH) were used for assessment of the antioxidant and anti-lipid peroxidation potentials of NS and onion extract. RESULTS: The lung of the nicotine-treated group exhibited emphysematous air spaces, collapsed corrugated alveoli with ruptured interalveolar septa in some specimen and thickened septa in the others, massive congestion, extravasation of red blood cells, inflammatory cellular infiltration and fluid exudate. Much improvement was observed in the onion-treated group despite the presence of residual pathological affection. The lung in the NS-treated group showed the nearly normal architecture with slight congestion. Administration of nicotine promoted lipid peroxidation (elevation of MDA) and decreased the level of the antioxidant markers (SOD, CAT, lung GSH and ELF GSH). With the use of onion extract and NS, the level of MDA decreased by 17.85% and 35.71% while the levels of SOD, CAT, GSH, and ELF GSH increased. The increase was more prominent in the NS-treated group. The levels in the NS-treated group reached nearly the level markers of the control group. CONCLUSIONS: Nigella sativa and onion extract attenuate the pathological effect of nicotine in the lung rats through antioxidative and anti-lipid peroxidative mechanisms with higher protection to NS.

Protective effect of omega 3 and vitamin D in preventing lung-tissue damage of newborn rats exposed to cigarette smoke during intrauterine period / Efecto protector de omega 3 y vitamina D en la prevención del daño en el tejido pulmonar de ratas recién nacidas expuestas al humo del cigarrillo durante el período intrauterino

SUMMARY: This study aimed to investigate the toxic effects of cigarette smoke exposure on lung and the protective role of Omega 3 and Vitamin D against these toxic effects biochemically and histologically. 28 pregnant Wistar Albino rats were divided into four groups. The first group was control group; the second group was exposed to smoke of 10 cigarette by puff device 2 hours/day after pregnancy; the third group was exposed to cigarette smoke together with Omega 3 (0.5 mg/kg/day) and the fourth group was exposed to cigarette smoke together with vitamin D (42 microgram/kg/day). Finally, lung tissue sections of the newborn rats were stained with Hemotoxilen eosine and Masson tricromite. Malondialdehyde (MDA) and Fluorescent Oxidation Products (FOU) levels were measured. Fetal weights and the number of fetuses were significantly lower in the group received only cigarette smoke (both p<0.001). Histopathologically, pulmonary volume, number of developed alveols and parenchyma elasticity decreased significantly, meanwhile interstitial tissue increased, elastin and collagen did not develop adequately. Histopathologic changes significantly decreased in the group given Omega 3 and Vitamin D. Statistically, MDA and FOU levels were found to be higher in the group exposed to cigarette smoke compared to the control group, and MDA and FOU levels were lower in the group given Omega 3 along with cigarette smoke (p<0.001). Cigarette smoke caused histologically significant damage to fetal lung tissue, oxidative stress and increased MDA and FOU levels. This damage was significantly reduced with Omega 3 and Vitamine D supplementation. Omega 3 is an important antioxidant; vitamin D has no significant antioxidant effect.

RESUMEN: Este estudio tuvo como objetivo investigar los efectos tóxicos de la exposición al humo de cigarrillo en el pulmón, y el papel protector de Omega 3 y la Vitamina D contra esos efectos. 28 ratas Wistar albino preñadas fueron separadas en cuatro grupos. El primer grupo grupo control; el segundo grupo estuvo expuesto al humo de 10 cigarrillos por dispositivo de inhalación 2 horas / día después de la preñez; el tercer grupo se expuso al humo del cigarrillo junto con Omega 3 (0,5 mg / kg / día) y el cuarto grupo se expuso al humo del cigarrillo junto con vitamina D (42 microgramos / kg / día). Secciones de tejido pulmonar de las ratas recién nacidas se tiñeron con Hematoxilina Eosina y tricrómico de Masson. Se midieron los niveles de malondialdehído (MDA) y productos de oxidación fluorescente (POF). Los pesos fetales y el número de fetos fueron significativamente más bajos en el grupo que recibió solamente humo de cigarrillo (ambos p <0,001). Histopatológicamente, el volumen pulmonar, el número de alveolos desarrollados y la elasticidad del parénquima disminuyeron significativamente; mientras que el tejido intersticial aumentó y la elastina y el colágeno no se desarrollaron adecuadamente. Los cambios histopatológicos disminuyeron significativamente en el grupo que recibió Omega 3 y Vitamina D. Estadísticamente, se encontró que los niveles de MDA y POF eran más altos en el grupo expuesto al humo de cigarrillo en comparación con el grupo control, además los niveles de MDA y POF fueron más bajos en el grupo que recibió Omega 3 junto con el humo del cigarrillo (p <0,001). El humo del cigarrillo causó daños histológicamente significativos en el tejido pulmonar fetal, el estrés oxidativo y el aumento de los niveles de MDA y FOU. Este daño se redujo significativamente con los suplementos de Omega 3 y Vitamina D. El omega 3 es un importante antioxidante; la vitamina D no tiene ningún efecto antioxidante significativo.

Protective effect of electro-acupuncture at maternal different points on perinatal nicotine exposure-induced pulmonary dysplasia in offspring based on HPA axis and signal transduction pathway.

Perinatal nicotine exposure can not only lead to lung dysplasia in offspring, but also cause epigenetic changes and induce transgenerational asthma. Previous studies have shown that electro-acupuncture (EA) applied to "Zusanli" (ST 36) can improve the lung morphology and correct abnormal expression of lung development-related protein in perinatal nicotine exposure offspring. However, it is still unclear whether ST 36 has a specific therapeutic effect and how maternal acupuncture can protect the offspring from pulmonary dysplasia. In this study, we compared the different effect of ST 36 and "Fenglong" (ST 40), which belong to the same meridian, in terms of lung pulmonary function and morphology, PPARγ, ß-catenin, GR levels in the lung tissues and CORT in the serum of perinatal nicotine exposure offspring, and explored the mechanism of acupuncture based on the maternal hypothalamus-pituitary-adrenal (HPA) axis. It is shown that EA applied to ST 36 could restore the normal function of maternal HPA axis and alleviate maternal glucocorticoid overexposure in offspring, thereby it can up-regulate the PTHrP/PPARγ and down-regulate the Wnt/ß-catenin signaling pathways, and protects perinatal nicotine exposure-induced pulmonary dysplasia in offspring. Its effect is better than that of ST 40. These results are of great significance in preventing perinatal nicotine exposure-induced pulmonary dysplasia in offspring.

Renoprotective effect of Spirulina platensis extract against nicotine-induced oxidative stress-mediated inflammation in rats.

BACKGROUND: Nicotine is an important factor in the pathogenesis of renal injury in smokers. PURPOSE: The purpose of the present study was to investigate the renoprotective effect of Spirulina platensis extract (SP) against chronic nicotine administration in rats. METHODS: Nicotine intoxication was induced with 0.5 mg/kg BW. Rats received 500 mg SP/kg BW by gastric gavage over 4 weeks. RESULTS: Our data revealed that nicotine induced renal dysfunction manifested by significant abnormal levels of kidney function markers (creatinine and urea) accompanied by increased levels of oxidative stress biomarker (malondialdehyde) and inflammatory markers (nitric oxide, Interleukin-6 and tumor necrosis factor-α) while antioxidant status as glutathione level and glutathione S-transferase activity were found to be decreased significantly as compared with controls. It is worthy to note that nicotine toxicity induced significant increments in the protein expression levels of nuclear factor kappa B as well as caspase-3. Histopathological observations showed tubular necrosis and congestion in the endothelial lining glomerular tuft and epithelial lining renal tubules with nicotine intoxication. Interestingly, our data demonstrated that SP supplementation significantly improved the nicotine-induced kidney dysfunction, alleviated the induced-lipid peroxidation, inflammatory, apoptotic protein markers, and boosted the enzymatic/non-enzymatic antioxidants. Moreover, it attenuated the nicotine-induced histopathological alterations of the kidney architecture. CONCLUSION: Thus, it is tempting to recommend dietary approaches with Spirulina platensis extract for smokers to minimize the deleterious effect of chronic nicotine consumption and smoke exposure-related problems towards kidney injury via the antioxidant, anti-inflammatory and antiapoptotic properties of Spirulina platensis.

Dietary DNA Attenuates the Degradation of Elastin Fibers in the Aortic Wall in Nicotine-Administrated Mice.

Abdominal aortic aneurysm (AAA) is a vascular disease characterized by chronic inflammation in the infrarenal aorta. Epidemiologic data have clearly linked tobacco smoking to aneurysm formation and a faster rate of expansion. It suggested that nicotine, one of the main ingredients of tobacco, has been suggested to be associated with AAA development and rupture. In the condition where no established drugs are available; therefore, an effective approach to prevent the vascular damage from nicotine consumption may be the use of dietary functional food factors. However, little is known about the relationship between dietary components and AAA. In this study, we estimated the effect of dietary deoxyribonucleic acid (DNA) on the vascular wall. After habituation for 5 d, the mice were divided into four groups: control diet and distilled water group (C), DNA-Na diet and distilled water group (DNA), control diet and 0.5 mg/mL nicotine solution group (C-Nic), DNA-Na diet, and 0.5 mg/mL nicotine solution group (DNA-Nic). The dietary DNA attenuated the degradation of elastin fibers induced by nicotine administration. The areas stained positive for MMP-2 in the DNA-Nic group were significantly suppressed compared to C-Nic mice. These data suggest that the dietary DNA may prevent the weakening of the aortic wall via inhibition of the MMP-2-dependent pathway. In conclusion, we have revealed the protective effect of dietary DNA on the vascular pathology of nicotine-administrated mice. A nucleic acid-rich diet might be useful for people who consume nicotine via smoking, chewing tobacco, or nicotine patches.

Targeting mitochondria with folic acid and vitamin B12 ameliorates nicotine mediated islet cell dysfunction.

Nicotine, one of the well-known highly toxic components of cigarette smoke, causes a number of adverse health effects and diseases. Our previous study has shown that nicotine induces reactive oxygen species (ROS) in islet cell and disrupts islet cell mitochondrial membrane potential (ΔΨm). However, supplementation with folic acid and vitamin B12 were found effective against nicotine induced changes in pancreatic islet cells. But the toxicological effects and underlying mechanisms of nicotine-induced mitochondrial dysfunction is still unknown. In this study, nicotine exposure decreases mitochondrial enzymes (pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, aconitase, malate dehydrogenase) activities by increasing cytosolic Ca2+ level which may contribute to increased mitochondrial ROS production by raising its flow to mitochondria. This in turn produces malondialdehyde and nitric oxide (NO) with a concomitant decrease in the activities of antioxidative enzymes and glutathione levels leading to loss of ΔΨm. Simultaneously, nicotine induces pancreatic islet cell apoptosis by modulating ΔΨm via increased cytosolic Ca2+ level, altered Bcl-2, Bax, cytochrome c, caspase-9, PARP expressions which were prevented by the supplementation of folic acid and vitamin B12 . In conclusion, nicotine alters islet cell mitochondrial redox status, apoptotic machinery, and enzymes to cause disruption in the ΔΨm and supplementation of folic acid and vitamin B12 possibly blunted all these mitochondrial alterations. Therefore, this study may help to determine the pathophysiology of nicotine-mediated islet cell mitochondrial dysfunction.

Potential amelioration of nicotine-induced toxicity by nanocurcumin.

Clinical Research Curcumin, a nontoxic bioactive agent of turmeric significantly reduces nicotine-induced toxicity both at cellular and genetic levels. The clinical implication of native curcumin is hindered in the target cells due to its low aqueous solubility, poor bioavailability and poor pharmacokinetics. The problem was tried to overcome by preparing nanocurcumin with a view to improve its aqueous solubility and better therapeutic efficacy against nicotine-induced toxicity. The prepared nanocurcumin was characterized by Ultraviolet-visible spectroscopy; Field emission scanning electron microscopy (FE-SEM); X-ray diffraction (XRD); and Fourier transform infrared spectroscopy (FTIR). Female albino rats of Wistar strain were daily exposed to effective dose of nicotine (2.5 mg/kg, injected subcutaneously) and supplemented with effective dose of curcumin (80 mg/kg body weight orally) or nanocurcumin (4 mg/kg body weight orally) for 21 days. The preventive efficacies of curcumin and nanocurcumin were evaluated against the changes in liver function enzymes, kidney function parameters, lipid profiles, lipid-peroxidation, anti-oxidant status, and tissues damages etc. Results revealed that nanocurcumin more effectively ameliorated the nicotine-induced toxicities at much lower concentration due to its higher aqueous solubility and more bioavailability. The nanocurcumin can be used as a potential therapeutic agent for better efficacy against nicotine-induced toxicities than native curcumin.

Transmucosal Delivery of Nicotine in Combination with Tincture of Benzoin Inhibits Apoptosis.

BACKGROUND AND OBJECTIVE: The aim of this study was to test the hypothesis that tincture of benzoin (TOB) facilitates immediate transmucosal nicotine absorption while simultaneously promoting a safe and sustained delivery of the nicotine. METHODS: In combination with TOB, nicotine toxicity and diffusion across human mucosal cells were measured using a 3-D human mucosal tissue model. RESULTS: Nicotine was delivered 2.1 times more quickly in combination with TOB than in combination with saline (p < 0.05). Despite the increased diffusion, nicotine in combination with TOB significantly increased mucosal cell survival (p < 0.05) by reducing the release of mitochondrial cytochrome c into the cytoplasm when compared with nicotine without TOB. The average percentage distribution of cytochrome c in the cytosolic fraction over time of nicotine + 79% ethyl alcohol (ETOH) versus nicotine plus TOB (79% ETOH) was significantly different over 120 min (60.0 ± 29.9% cytosol, 16.1 ± 9.4% cytosol, p = 0.03). Related to the reduction of cytochrome c release into the cytoplasm, TOB suppressed caspase-3 and -9 activity, thereby preventing intrinsic apoptosis and providing cytoprotection of the mucosal cells (ETOH + nicotine vs ETOH + nicotine + TOB: p = 0.008 for caspase 3, p < 0.001 for caspase 9). CONCLUSION: Two hours of TOB (17-24% benzoin, 79% ETOH) plus nicotine promotes diffusion of nicotine across human mucosal cells and simultaneously prevents human mucosal cell toxicity by inhibiting cytochrome c release into the cytosol, thereby preventing caspase 3 and 9 activity and subsequent intrinsic apoptosis.

Age-dependent sensitivity of the mouse kidney to chronic nicotine exposure.

BackgroundMany adolescents are exposed to nicotine via smoking, e-cigarette use, or second-hand smoke. Nicotine-induced renal oxidative stress and its long-term consequences may be higher in adolescents than in adults because of intrinsic factors in the adolescent kidney.MethodsAdolescent and adult male C57Bl/6J mice were subjected to 2 or 200 µg/ml nicotine, which closely emulates passive or active smoking, respectively, for 4 weeks. Extent of nicotine exposure (cotinine content), oxidative stress (HNE), renal function (creatinine), tubular injury (KIM-1), and pretreatment renal levels of select pro-oxidant (p66shc) and antioxidant (Nrf2/MnSOD) genes were determined. Impact of p66shc overexpression or Nrf2/MnSOD knockdown on low-/high-dose nicotine-induced oxidative stress was determined in cultured renal proximal tubule cells.ResultsDespite similar plasma/renal cotinine levels, renal HNE and KIM-1 contents were higher in adolescents compared with those in adults, whereas renal function was unaltered after passive or active smoking-equivalent nicotine exposure. Pretreatment levels of p66shc were higher, whereas Nrf2/MnSOD levels were lower in the adolescent kidney. In agreement with this, overexpression of p66shc or knockdown of Nrf2/MnSOD augmented nicotine-induced ROS production in renal proximal tubule cells.ConclusionChronic nicotine exposure incites higher oxidative stress in the adolescent than in adult kidney because of a pre-existent pro-oxidant milieu.

Selenium nanoparticles with low-level ionizing radiation exposure ameliorate nicotine-induced inflammatory impairment in rat kidney.

Occupational exposure to low-level ionizing radiation (<1 Gy) was shown to enhance cell protection via attenuating an established inflammatory process. Nicotine, a major toxic component of cigarette smoke, is responsible for smoking-mediated renal dysfunction. The present study was therefore aimed to investigate the protective impact of ginger Zingiber officinale selenium nanoparticles (SeNPs) with whole-body low-dose gamma radiation (γ-R) against nicotine-induced nephrotoxicity in male albino rats. Nicotine intoxication was induced with 0.5 mg/kg BW. Rats received 0.1 mg SeNPs/kg BW by gastric gavage concomitant with 0.5 Gy γ-R over 4 weeks. Characterization studies showed the formation of spherical SeNPs with a size ranged from 10 to 30 nm in diameter with a thin film encapsulating the nanoballs. Our data revealed that nicotine induced renal dysfunction manifested by significant abnormal levels of kidney function markers (creatinine, urea, sodium and potassium) accompanied by increased levels of malondialdehyde along with a reduction in glutathione level, glutathione peroxidase, and glutathione S-transferase activities. It is worthy to note that nicotine toxicity induced significant increments in serum inflammatory markers: tumor necrosis factor-α and vascular cell adhesion protein 1. Western blotting showed marked significant elevation in caspase-3 activities against nicotine. The mRNA gene expression of inducible cyclooxygenase-2 gene was highly increased with nicotine intoxication while that of cyclooxygenase-1 did not show any changes. Interestingly, our data demonstrated that SeNPs in synergistic interaction with γ-R are efficacious control against nicotine-induced nephrotoxicity via anti-oxidant-mediated anti-inflammatory activities. Thus, it is tempting to recommend dietary approaches with ginger SeNPs for smokers at workplaces exposed occupationally and regularly to low-level ionizing radiation.

Camellia sinensis Prevents Perinatal Nicotine-Induced Neurobehavioral Alterations, Tissue Injury, and Oxidative Stress in Male and Female Mice Newborns.

Nicotine exposure during pregnancy induces oxidative stress and leads to behavioral alterations in early childhood and young adulthood. The current study aimed to investigate the possible protective effects of green tea (Camellia sinensis) against perinatal nicotine-induced behavioral alterations and oxidative stress in mice newborns. Pregnant mice received 50 mg/kg C. sinensis on gestational day 1 (PD1) to postnatal day 15 (D15) and were subcutaneously injected with 0.25 mg/kg nicotine from PD12 to D15. Nicotine-exposed newborns showed significant delay in eye opening and hair appearance and declined body weight at birth and at D21. Nicotine induced neuromotor alterations in both male and female newborns evidenced by the suppressed righting, rotating, and cliff avoidance reflexes. Nicotine-exposed newborns exhibited declined memory, learning, and equilibrium capabilities, as well as marked anxiety behavior. C. sinensis significantly improved the physical development, neuromotor maturation, and behavioral performance in nicotine-exposed male and female newborns. In addition, C. sinensis prevented nicotine-induced tissue injury and lipid peroxidation and enhanced antioxidant defenses in the cerebellum and medulla oblongata of male and female newborns. In conclusion, this study shows that C. sinensis confers protective effects against perinatal nicotine-induced neurobehavioral alterations, tissue injury, and oxidative stress in mice newborns.

Ameliorative effects of Achillea millefolium inflorescences alcoholic extract against nicotine-induced reproductive failure in rat.

BACKGROUND: Nicotine (Nic) is a major risk factor in the development of functional disorders of male reproductive system. Achillea millefolium; is highly regarded for medicinal activities, due to its antioxidant and anti-inflammatory properties. This study was carried out to evaluate whether Achillea millefolium (Achm) inflorescences alcoholic extract could serve as a protective agent in male reproductive male failures during Nic exposure in a rat model. METHODS: Twenty-five adult male Wistar rats were categorized into the five groups. Tests 1 and 3 groups were received Nic at dose levels of 0.2 and 0.4mg/kg BW/day, respectively by IP injection. Tests 2 and 4 groups were received Nic at the same doses along with Achm at dose level of 120mg/kg BW/day. The study period took forty-eight days for all experimental groups. RESULTS: Nic groups showed significant decreases in tubule differentiation index (TDI), sperm count, motility, stereological parameters and an increase in dead and abnormal sperms. Moreover, the reduction in total antioxidant capacity (TAC), superoxide dismutase (SOD) activity, serum levels of FSH, LH and testosterone, along with increased serum concentration of LDH were observed in the Nic groups. Total nitrite and malondealdehyde levels increased and total thiol molecules (TTM) levels decreased in testicular tissue in the Nic groups. Notably, Achm co-administration caused a contemporary recovery in above-mentioned parameters. CONCLUSION: Nic exerts major toxicity in testicular tissue and causes damages in several ways including, oxidative stress, whilst Achm imposes protective effect against Nic-induced reproductive failure, which may attribute to its antioxidant capacity.

Application of cDNA-AFLP to biomarker exploration in a non-model species Grandidierella japonica.

Biomarkers of exposure can be used to identify specific contaminants that are adversely affecting aquatic organisms. However, it remains prohibitively costly to investigate multiple novel biomarkers of exposure in a non-model species, despite the development of next-generation sequencing technology. In this study, we focused on the use of cDNA-amplified fragment length polymorphism (AFLP) as a cost-effective biomarker discovery tool to test whether it could identify biomarkers of exposure in the non-model amphipod species Grandidierella japonica. Loci were identified that were differentially expressed in amphipods exposed to reference chemicals (Cu, Zn, and nicotine) and to an environmental sample (road dust) at sublethal concentrations. Eight loci were shown to respond consistently to nicotine at different concentrations, but not to Cu or Zn. Some of the loci also responded to an environmental road dust sample containing nicotine. These findings suggest that loci identified using cDNA-AFLP could be used as biomarkers of nicotine exposure in environmental samples with complex matrices. Further studies with other organisms and toxicants are needed, but we have demonstrated that the use of cDNA-AFLP to identify biomarkers for ecotoxicological studies of non-model species is at least feasible.