Biomedical subjects

C H Cho

Publications and source records attributed to C H Cho.

At least 37 records · Page 2Linked to original sources

PubMed2001

A mechanistic study of proliferation induced by Angelica sinensis in a normal gastric epithelial cell line.

It has been reported that an extract from Angelica sinensis mainly consisting of polysaccharides (95%) prevented ethanol- or indomethacin-induced gastric mucosal damage (Cho CH et al. Planta Med 2000;66:348-51). However, it is not known whether Angelica sinensis has a direct stimulatory effect on the healing of gastric mucosal lesions. To study the hypothesis that Angelica sinensis has a direct mucosal healing effect in rats and in isolated gastric epithelial cells, we assessed the wound repair in both animals and normal cell culture (RGM-1), as well as [3H]thymidine incorporation, ornithine decarboxylase (ODC) activity, and ODC protein and c-Myc protein expression after different treatments in RGM-1 cells. We found that Angelica sinensis crude extract (ASCE) dose-dependently enhanced gastric ulcer healing in rats and promoted wound repair in RGM-1 cells. It also significantly stimulated [3H]thymidine incorporation and ODC activity in RGM-1 cells in a concentration-dependent manner. ODC and c-Myc protein expression was also increased as a result of this process. DL-alpha-difluoromethyl-ornithine repressed the [3H]thymidine incorporation and ODC activity induced by ASCE. Pretreatment with c-Myc antisense oligodeoxynucleotides blocked the stimulatory action of ASCE on [3H]thymidine incorporation and ODC protein expression. These data suggest that ASCE has a direct mucosal healing effect on gastric epithelial cells, while ODC and c-Myc are closely associated with this effect.

Angelica sinensis↗

PubMed2001

Arsenic trioxide induces apoptosis in human gastric cancer cells through up-regulation of p53 and activation of caspase-3.

Arsenic trioxide (As(2)O(3)) can induce clinical remission in patients suffering from acute promyelocytic leukemia, through induction of apoptosis and activation of caspases. We investigated the potential use of As(2)O(3) in human gastric cancer and its possible mechanisms. Human gastric cancer cell lines AGS and MKN-28 were treated with various concentrations (0.1 to 100 microM) of As(2)O(3) for 24 to 72 hr. Apoptosis was determined by acridine orange staining, flow cytometry and DNA fragmentation. Protein levels of p53, p21(waf1/cip1), c-myc, bcl-2 and bax were detected by Western blotting. Effects of As(2)O(3) on caspase-3 protease activity, its protein concentration and cleavage of poly(ADP)-ribose polymerase (PARP) were also studied. As(2)O(3) inhibited cell growth and induced apoptosis in both cell lines, though AGS cells were more sensitive. As(2)O(3) induced apoptosis in AGS cells in a concentration- and time-dependent manner. Treatment resulted in a marked increase in p53 protein levels as early as 4 hr. Co-incubation with p53 anti-sense oligo-nucleotide suppressed As(2)O(3)-induced intracellular p53 over-expression and apoptosis. As(2)O(3) increased the activity of caspase-3, with appearance of its 17 kDa peptide fragment, and cleavage of PARP, with appearance of the 85 kDa cleavage product, both in parallel with the induction of apoptosis. Both the tripeptide caspase inhibitor zVAD-fmk and the specific caspase-3 inhibitor DEVD-fmk partially suppressed As(2)O(3)-induced caspase-3 activation and apoptosis. As(2)O(3) inhibits cell growth and induces apoptosis in gastric cancer cells, involving p53 over-expression and activation of caspase-3. The potential use of this compound in the treatment of gastric cancer is worth further investigation.

Amino Acid Chloromethyl Ketones↗

PubMed2001

Angelica sinensis modulates migration and proliferation of gastric epithelial cells.

A crude extract from Angelica sinensis (ASCE), which mainly consists of polysaccharides, prevents ethanol- or indomethacin-induced gastric mucosal damage and promotes ulcer healing. The aim of this study was to test the hypothesis that ASCE has a direct stimulating effect on gastric epithelial cells for wound healing. We found that ASCE significantly promoted the migration of epithelial cells over an artificial wound on the surface of an RGM-1 monolayer. The extract also stimulated DNA synthesis in a dose-dependent manner and concomitantly increased EGF mRNA expression. Co-incubation of ASCE with anti-EGF antibody reduced the speed of migration and the DNA synthesis, which however were still higher than the control without ASCE. These results strongly suggest that ASCE has a direct wound healing effect on gastric mucosa, and this is acting partially through an EGF-mediated pathway.

Animals↗

PubMed2001

Increased erythritol production in fed-batch cultures of Torula sp. by controlling glucose concentration.

The effect of glucose concentration on erythritol production by Torula sp. was investigated. The maximum volumetric productivity of erythritol was obtained at an initial glucose concentration of 300 g l(-1) in batch culture. The volumetric productivity was maximal at a controlled glucose concentration of 225 g l(-1), reducing the lag time of the erythritol production. A fed-batch culture was established with an initial glucose concentration of 300 g l(-1) and with a controlled glucose concentration of 225 g l(-1) in medium containing phytic acid as a phosphate source. In this fed-batch culture, a final erythritol production of 192 g l(-1) was obtained from 400 g l(-1) glucose in 88 h. This corresponded to a volumetric productivity of 2.26 g l(-1) h(-1) and a 48% yield.

Cell Division↗

PubMed2001

High prevalence of mixed infections by Helicobacter pylori in Hong Kong: metronidazole sensitivity and overall genotype.

BACKGROUND: Diversity in metronidazole susceptibility and genotypes of Helicobacter pylori have been reported with varying results in different areas. AIMS: To investigate the prevalence of multiple strain infection in a symptomatic Chinese population and to determine the metronidazole susceptibility pattern and genotypic characteristics of these infecting strains. METHODS: Gastric biopsies from antrum, body and cardia were taken during upper endoscopy in symptomatic patients referred to our department. Pooled cultures and single colony isolates were obtained and tested for metronidazole susceptibility and random amplified polymorphic DNA (RAPD) fingerprint patterns. RESULTS: A total of 461 isolates were successfully cultured from 46 patients. Fifty-seven per cent of subjects had metronidazole-resistant strains. Among them, 77% carried a mixture of sensitive and resistant strains, non-uniformly distributed in the gastric mucosa. Mixed genotypes were found by RAPD typing in 24% of subjects. These did not correlate with the metronidazole susceptibility/resistance pattern. CONCLUSION: H. pylori infections with mixed metronidazole sensitive/resistant strains and mixed genotypes are common in Hong Kong. This makes it prudent to use bacterial strains from several biopsy sites when testing for traits such as drug resistance or virulence in relation to disease.

Adult↗

PubMed2001

Epidermal growth factor and its receptor in chronic active gastritis and gastroduodenal ulcer before and after Helicobacter pylori eradication.

BACKGROUND: Helicobacteria pylori infection of gastroduodenal mucosa is strongly associated with gastritis and peptic ulcer disease. The aims of the present study were to compare the gastroduodenal mucosal levels of epidermal growth factor (EGF) and its receptor (EGFR) among H. pylori-negative controls and H. pylori infected patients with chronic active gastritis or gastroduodenal ulcer before and after H. pylori eradication. METHODS: The protein levels of EGF in mucosal tissues and saliva were determined by a solid-phase enzyme-linked immunosorbent assay (ELISA). Repeat transcription-polymerase chain reaction and the following polymerase chain reaction ELISA were employed to examine the mucosal EGFR mRNA expression. RESULTS: Mucosal injury and H. pylori infection increased EGF protein levels and EGFR mRNA expression in the antral mucosa. The concentration of EGF in saliva was not affected by mucosal damage or H. pylori infection. Successful H. pylori eradication normalized the EGFR mRNA back to its basal level 6 weeks after treatment. However, after unsuccessful eradication their high levels in the antrum persisted. All patients experienced ulcer healing after drug treatment, regardless of H. pylori eradication. CONCLUSIONS: Mucosal damage increased the expression of EGF protein and EGFR mRNA in the gastric mucosa. H. pylori could induce the expression of EGFR but not the EGF in the antral mucosa. The expression of EGFR could be a contributing factor for ulcer healing in patients with H. pylori infection.

Adolescent↗

PubMed2001

A 3.0-kDa low molecular weight heparin promotes gastric ulcer healing in rats.

BACKGROUND: Previous studies have shown that intragastric administration of unfractionated heparin enhances gastric ulcer healing in rats. As the large molecule of heparin may be partially degraded in the upper gastrointestinal tract, it is likely that fragments of heparin, derived from the unfractionated parent compound, are involved in the anti-ulcer action in the stomach. Therefore, it is possible that low molecular weight heparin may have a similar ulcer healing effect. METHODS: Male Sprague-Dawley rats with acetic acid-induced gastric ulcers were given a 3.0-kDa low molecular weight heparin (0.6-6.0 mg/kg) intravenously or intragastrically once daily for 4 days. Ulcer healing, mucosal histological changes, angiogenesis and gastric mucus production both in vivo and in vitro were determined. The bleeding time was measured to indicate the anticoagulation activity. RESULTS: Both intravenous and intragastric low molecular weight heparin dose dependently accelerated gastric ulcer healing, which was accompanied by a significant increase in mucosal regeneration and proliferation, angiogenesis and mucus content in the stomach. The drug also stimulated the mucus production in MKN-28 cells. Drug administration by either route did not alter the bleeding time in rats. CONCLUSIONS: A 3.0-kDa low molecular weight heparin possesses an ulcer healing effect similar to that of unfractionated heparin in the stomach of the rat. This smaller molecular drug is superior to the unfractionated form, does not affect the coagulation activity and may show better absorption in the gastrointestinal tract.

Animals↗

PubMed2001

Influence of gender difference and gastritis on gastric ulcer formation in rats.

BACKGROUND: Male patients with gastritis are found to have a high risk of developing peptic ulcer diseases. However, how gastritis or gender difference affects gastric ulcer formation is unclear. The present study aimed to investigate the relationship between ethanol-induced acute gastritis and gastric ulcer formation in rats. METHODS: Acute gastritis or gastric ulcer was induced in the rat stomach by 80% ethanol or 60% acetic acid, respectively. Rats were killed either with gastritis alone or thereafter at day 1, 3 or 6 after ulcer induction. The number of proliferating and apoptotic cells, the mucosal mucus and prostaglandin E(2) (PGE(2)) level were also determined. RESULTS: Male rats with acute gastritis potentiated gastric ulcer formation, while gastritis in female rats prevented ulceration. Female rats with gastritis had a significantly faster ulcer-healing rate. More apoptotic cells were found in the gastritis groups, but only the female gastritis group produced more proliferating cells and had a decrease in the apoptosis-over-proliferation ratio. The mucus level was higher in female rats after ulcer induction. Mucosal PGE(2) level was higher in female rats with acute gastritis. Both mucus and PGE(2) were increased during ulcer healing in both genders. CONCLUSIONS: This study shows that gender difference plays a role in the pathogenesis of ulcer formation. The number of cells with apoptosis or proliferation determines, in part, the gender difference on gastric ulcer formation in rats. Gastric PGE(2) not only contributes to this process, but also together with gastric mucus participates in the ulcer-healing process in the stomach.

Animals↗

PubMed2001

Interleukin-1beta induces cyclo-oxygenase-2 expression in gastric cancer cells by the p38 and p44/42 mitogen-activated protein kinase signaling pathways.

BACKGROUND AND AIMS: Cyclo-oxygenase-2 (COX-2) is the inducible enzyme in the gastric mucosa responsible for prostaglandin production during inflammation and ulcer healing. The regulation of COX-2 gene expression in gastric epithelial cells is not well understood. In this study, we investigated the effect of interleukin (IL)-1beta on COX-2 expression in the human gastric cancer cell, and explored the signaling pathways involved. METHODS: Gastric cancer cell line AGS was treated with IL-1beta or the inhibitors of mitogen-activated protein-Erk kinase (MEK) and p38 mitogen-activated protein (MAP) kinase prior to the addition of IL-1beta. The COX-2 mRNA or protein levels were measured by using RT-PCR or western blot analysis, respectively. Prostaglandin E2 (PGE2) production/secretion was determined by using the prostaglandin E2 EIA assay. The phosphorylation/activation of p44/42 and p38 MAP kinases were determined by using western blot analysis and using phospho-specific antibodies. RESULTS: Interleukin-1beta treatment dose- and time-dependently increased COX-2 mRNA and protein expression levels, and enhanced PGE2 production/secretion in AGS cells. In contrast, IL-1beta had no effect on the level of the constitutively expressed COX-1. In parallel to the increase of COX-2, we showed that p44/42 and p38 MAP kinase activities were also upregulated by IL-1beta treatment. To demonstrate the cause-effect relationship, we showed that inhibition of MEK and p38 MAP kinase with specific inhibitors suppressed IL-1beta-mediated increases in COX-2 mRNA and protein levels, and the PGE2 production. CONCLUSIONS: Our results demonstrated that in human gastric cancer cells, IL-1beta upregulates the COX-2 gene expression through the activation of MEK/p44/42 and p38 MAP kinases pathway.

Adenocarcinoma↗

PubMed2001

Macrophage migration inhibitory factor is an important mediator in the pathogenesis of gastric inflammation in rats.

BACKGROUND & AIMS: Macrophage migration inhibitory factor (MIF) has been shown to play a pivotal role in inflammatory and immune-mediated diseases. This study investigates the role of MIF in gastric inflammation. METHODS: Expression of MIF was examined in a rat gastric ulcer model induced by acetic acid, and the functional role of MIF in acute gastric ulcer was investigated by administration of a neutralizing anti-MIF antibody. RESULTS: MIF messenger RNA and protein were markedly up-regulated in acute gastric ulcer, which correlated with the accumulation of macrophages (P < 0.001) and neutrophils (P < 0.05) at the site of inflammation. Macrophages, like neutrophils, were the major inflammatory cells infiltrating the ulcer base and they strongly expressed inducible nitric oxide synthase. However, macrophages, not neutrophils, were a rich source of MIF production in acute gastric ulcer. In vivo and in vitro blockade of MIF with the neutralizing anti-MIF antibody significantly inhibited the marked up-regulation of MIF, tumor necrosis factor alpha, inducible nitric oxide synthase, and intercellular adhesion molecule-1. This was associated with the marked inhibition of macrophage (70% reduced) and neutrophil (60% reduced) accumulation and activation, thus reducing ulcer sizes and attenuating ulceration. CONCLUSIONS: This study has shown that MIF was markedly up-regulated during acute gastric ulcer. Inhibition of acute gastric ulcer by blockade of MIF indicates that MIF is a key inflammatory mediator and plays a pathogenic role in gastric inflammation.

Acetic Acid↗

PubMed2001

The role of nitric oxide on cigarette smoke-induced programmed cell death in the gastric mucosa.

BACKGROUND: This study was designed to investigate the effect of cigarette smoking on apoptosis in the gastric mucosa and the role of nitric oxide (NO) in the gas phase and extracts in the tar phase in this pathological process. METHODS: Male Sprague-Dawley rats and human gastric epithelial cell line AGS were used in the study. RESULTS: Cigarette smoking significantly increased apoptotic bodies in the rat gastric mucosa. However, neither filtered cigarette smoke, in which most of the substances in the tar phase were removed, nor oral administration of the two cigarette smoke extracts produced any effect on apoptosis. Interestingly, in this experiment pretreatment with a NO donor, the chloroform extract (CE) could significantly increase apoptosis. In in vitro study, only the CE induced DNA fragmentation, which could be elevated further by preincubation with a NO donor. The same extract also elevated inducible nitric oxide synthase (iNOS) activity. Inhibition of iNOS by N(G)-nitro-L-arginine methylester hydrochloride (L-NAME) partially abolished CE-induced apoptosis. CONCLUSIONS: These findings suggested that exogenous and endogenous NO had a synergistic effect with substances in the tar phase to induce programmed cell death in gastric epithelial cells both in vivo and in vitro.

Analysis of Variance↗

PubMed2001

12-Lipoxygenase inhibition induced apoptosis in human gastric cancer cells.

Arachidonic acid release from membrane phospholipids is essential for tumour cell proliferation. Lipoxygenases constitute a pathway for arachidonate metabolism. The present study investigated the expression of 12-lipoxygenase and its effect on cell proliferation as well as survival in two human gastric cancer cell lines (AGS and MKN-28). RT-PCR and western blots, respectively, showed 12-LOX mRNA and protein expression in both AGS and MKN-28 cell lines. Treatment with a 12-LOX inhibitor, baicalein, significantly inhibited cancer cell proliferation, but a metabolite of 12-LOX activity, 12 hydroxyeicosatetraenoic acid (12-HETE) reversed baicalein-induced growth inhibition. Furthermore, the blockade of the 12-LOX pathway through a 12-LOX inhibitor and antisense induced apoptosis of gastric cancer cell lines. The biochemical characteristics of apoptosis were p53-independent combined with a decrease in bcl-2 expression. Caspase-7 was proteolytically activated and responsible for the apoptosis execution.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed2001

Protective role of heme oxygenase-1 on trinitrobenzene sulfonic acid-induced colitis in rats.

Preliminary studies showed that the inducible form of heme oxygenase (HO-1) was induced and played a protective role in the process of inflammation. The present study investigated the possible role of HO-1 in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. We measured HO-1 activity in TNBS-induced colitis in rats and analyzed the severity of colitis along with altered HO activity by assessing lesion area and myeloperoxidase activity. HO-1 mRNA and protein expressions were determined at different time points after TNBS induction. Free radical production and inducible nitric oxide synthase (iNOS), which participate in oxidative injury, were also assayed. HO activity and HO-1 gene expression increased markedly after TNBS induction. Administration with tin mesoporphyrin (SnMP), a HO inhibitor, potentiated the colonic damage along with a reduction in HO-1 activity. Furthermore, the reduction of HO-1 expression by SnMP also enhanced reactive oxygen species and iNOS expression, both of which were dramatically increased after the TNBS enema. L-Arginine pretreatment further aggravated the injurious action of SnMP. Our results indicate that HO-1 plays a protective role in the colonic damage induced by the TNBS enema, and the preventive effects probably result from decreased free radical production and inhibition of iNOS expression in colonic tissues.

Animals↗

PubMed2001

Inducible HSP70 mediates delayed cardioprotection via U-50488H pretreatment in rat ventricular myocytes.

To test the hypothesis that heat-shock proteins (HSPs) mediate delayed cardioprotection of prior kappa-opioid receptor (kappa-OR) stimulation, we first correlated cellular injury and viability with the expression of HSP70s in isolated rat ventricular myocytes subjected to prior kappa-OR stimulation with the selective agonist trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide (U-50488H) and delayed lethal simulated ischemia (LSI). Cell injury and viability were indicated by lactate dehydrogenase release and trypan blue exclusion, respectively. The reduced injury and increased viability after pretreatment with U-50488H were concentration dependent and correlated directly with the expression of both stress-inducible (HSP70) and constitutive (HSC70) proteins. The effects mimic those with metabolic inhibition preconditioning (MIP). The cardioprotection against LSI by pretreatment with U-50488H and MIP was abolished and antagonized, respectively, via blockade of the kappa-OR by its selective antagonist, nor-binaltorphimine. We also found that blockade of the production of HSP70 but not HSC70 blocked the inhibitory effect of pretreatment with U-50488H on injury and viability. These observations provide evidence that stress-inducible HSP70 mediates delayed cardioprotection of prior kappa-OR stimulation.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed2001

Aggravating effect of cigarette smoke exposure on experimental colitis is associated with leukotriene B(4) and reactive oxygen metabolites.

BACKGROUND/AIMS: Cigarette smoking is closely related to the development and recurrence of inflammatory bowel disease (IBD). The present study aimed to investigate the underlying mechanisms of the adverse action of cigarette smoke (CS) exposure on trinitrobenzene sulfonic acid (TNBS)-induced IBD. METHODS: Rats were preexposed to CS once daily for 4 days before receiving a TNBS enema, and they were killed 24 h afterwards. The colonic myeloperoxidase (MPO) and xanthine oxidase (XO) activities, leukotriene B(4) (LTB(4)) and glutathione (GSH) levels, as well as the production of reactive oxygen metabolites (ROMs) were measured. RESULTS: CS preexposure significantly augmented the adverse effects of the TNBS enema on colonic damage and increase in MPO activity, while it did not significantly alter the XO activity. Meanwhile, the elevation of ROM production and LTB(4) concentration in colonic tissues after the TNBS enema was also markedly enhanced by CS exposure. In contrast, the depressive action of the TNBS enema on cellular antioxidant GSH levels was reduced further by CS exposure. Pretreatment with a specific LTB(4) antagonist, ONO-4057, protected against colonic damage, particularly in the CS group. CONCLUSION: CS exposure aggravated experimental IBD. This adverse action could be due to the depletion of GSH together with overproduction of LTB(4), followed by the accumulation of neutrophils and ROMs in the colonic tissue.

Analysis of Variance↗

PubMed2001

Hepatotoxicity of prenatal and postnatal exposure to nicotine in rat pups.

Prenatal and postnatal exposure to nicotine have been shown to affect developing tissues in growing animals. Rat pups were exposed to nicotine prenatally and/or postnatally for 10 days by feeding pregnant and lactating rat dams water containing 0, 54, or 108 microM of nicotine. Nicotine exposure did not affect either litter sizes or body weights at birth and at 10 days of age. Exposure to 108 microM of nicotine prenatally increased significantly the incidence of focal necrosis at birth, and the liver damage was still evident at 10 days of age even after the pups were allowed to suckle dams not exposed to any nicotine during the study period. Continuation of nicotine exposure postnatally increased the incidence and severity of focal and confluent necrosis. Postnatal exposure to 108 microM of nicotine to pups not previously exposed also increased the incidence of mild focal and confluent necrosis, although not significantly. Exposure to nicotine prenatally did not affect liver malondialdehyde (MDA) levels at birth. However, liver MDA was significantly lower in rat pups exposed to nicotine prenatally when they were 10 days of age irrespective of whether there were further exposure to nicotine postnatally. Reasons for the late onset of the low MDA levels need further investigation. Postnatal nicotine exposure to either 54 or 108 microM of nicotine to pups not previously exposed fails to affect liver MDA at 10 days of age. The significant decrease in hepatic superoxide dismutase (SOD) levels reflects those of hepatic injury, indicating the possibility of a nicotine-induced downregulation of SOD enzyme production.

Animals↗

PubMed2001

Therapeutic potential of oestrogen receptor ligands in development for osteoporosis.

Accelerated bone loss secondary to loss of ovarian function at menopause is well recognised as a major risk factor for osteoporotic fractures in postmenopausal women. Postmenopausal bone loss can be prevented or arrested by oestrogen replacement therapy (ERT). It has also been reported that ERT protects against cardiovascular disease by improving the serum lipid profile, however there are mixed reports concerning these benefits. Unopposed ERT causes an unacceptable increase in the risk of endometrial cancer and proliferative effects in mammary tissue resulting in an increased risk of breast cancer. While this can be counteracted by combining ERT with a low-dose of a progestin, withdrawal bleeding and the continuing uncertainty about the effect of oestrogen on the risk of breast cancer contribute to poor compliance for long-term use. Because of the known and suspected risks of oestrogen therapy it has been estimated that in the US < 40% of women on ERT will continue treatment beyond one year. An ideal therapy would retain the desirable skeletal and cardiovascular effects of oestrogen, lack oestrogenic activity on the endometrium and reduce the incidence of breast cancer. The concept of selective oestrogen receptor modulation (SERM) has been demonstrated for a number of compounds including tamoxifen, raloxifene, droloxifene, GW-5638 and levormeloxifene. However, the clinical utility of these agents will depend on the profile of tissue-specific effects and the extent to which they are translated into in vivo efficacy. A SERM is defined as a compound that has oestrogen agonism on one or more of the desired target tissues, such as bone or liver, and has antagonism and/or minimal agonism (i.e., clinically insignificant) in reproductive tissue, such as the breast or uterus. Although tamoxifen acts as a SERM, it is also associated with an increased incidence (4% gynaecological symptoms greater than placebo control) of endometrial cancer. Indeed, there have been a number of mechanistic-based studies to explain the increased incidence of endometrial carcinomas in tamoxifen treated patients, which provide an in vitro insight into the adverse clinical observations in vivo. Attempts to improve on the pharmacological profile of tamoxifen have resulted in compounds that differ in their oestrogen agonist/antagonist characteristics, including the pure oestrogen antagonists. This suggests that it may be possible to develop a molecule with a desired profile of tissue-specific agonist/antagonist activities by establishing bone and cardiovascular protective effects but having no effects (or even behaving as an antagonist) in the reproductive tissues.

Journal Article↗

PubMed2001

Beneficial intervention of experimental colitis by passive cigarette smoking through the modulation of cytokines in rats.

BACKGROUND: Epidemiologic observations have indicated that cigarette smoking decreases the risk of ulcerative colitis, but the modes of action remain anonymous. The present study aimed to investigate the beneficial effects of passive cigarette smoking using an animal colitis model. We hypothesized that the underlying mechanisms may involve immunoregulation of cytokines. METHODS: Experimental colitis was induced in rats by enema administration of 2,4-dinitrobenzene sulfonic acid (DNBS). Passive cigarette smoking by rats was performed for 1 hour once daily, from 3 days before DNBS enema until they were sacrificed on day 8. Other groups of DNBS-treated rats received therapeutic treatment of cyclosporin A or pentoxifylline, a tumor necrosis factor (TNF)-alpha inhibitor. Macroscopic and histologic damage were graded, and the colonic levels of different cytokines and the levels/activities of parameters related to neutrophil activation were also measured. RESULTS: DNBS-induced colonic damage was improved in passive-cigarette-smoking rats. This was accompanied by attenuation of the elevated colonic myeloperoxidase and inducible nitric oxide synthase activities and leukotriene B4 level. Likewise, the augmentation in colonic levels of TNF-alpha, interleukin (IL)-1 beta, and IL-6 in colitis rats was also alleviated by passive cigarette smoking. In contrast, the deprivation of colonic IL-10 during colitis was preserved in cigarette-smoking rats. These effects were similarly accomplished by pentoxifylline and, to some degree, by cyclosporin A. CONCLUSIONS: The results support the idea that the beneficial effects of passive cigarette smoking in experimental colitis involved immunoregulation of cytokines in colonic tissues.

Animals↗