Saffron is a well-known spice produced from dried stigmas of Crocus sativus L. flowers. Apart from its wide use in food preparations, it also has a broad range of medical properties. We examined the potential anti-inflammatory effects of saffron ethanolic extract (SEE) using an animal model of arthritis. Adjuvant-induced arthritis was induced in Wistar rats by injection of Complete Freund's Adjuvant. The rats were then injected intraperitoneally every other day with 25–600 mg SEE/kg or dexamethasone (DEX, 2 mg/kg). Changes in body weight, paw oedema and arthritis indices were recorded over the subsequent 12 days of treatment. Results revealed that SEE particularly at the higher concentrations significantly reduced paw and tibiotarsal joint diameters and comparing with DEX caused no significant change in body weight. These observations suggest that SEE displays a considerable anti-inflammatory potency and could potentially be used as an anti-arthritic agent in control of inflammation in rheumatoid arthritis. 相似文献
Truncal vagotomy is known to aggravate the damaging effects of alcohol-induced gastric injury and prevent the occurrence of adaptive cytoprotection against such injury by a mild irritant. This study was undertaken to determine whether aberrations in glutathione (GSH) metabolism were responsible for these vagotomy-induced effects. Fasted rats (6–8/group) were subjected to truncal vagotomy and pyloroplasty or sham vagotomy and pyloroplasty. One week later they were given 2 ml of oral saline or the mild irritant, 25% ethanol (EtOH). Thirty minutes following such treatment, animals were either sacrificed or orally received 2 ml of 100% EtOH and then were sacrificed 5 min later. At sacrifice, in each experimental group, stomachs were removed and either evaluated macroscopically for the degree of injury involving the glandular gastric epithelium or samples of the mucosa were prepared for measurement of total GSH levels or GSH peroxidase (GPX) and GSH reductase (GRT) activity. In nonvagotomized animals, saline treatment prior to 100% EtOH exposure resulted in injury to the glandular epithelium involving approximately 18%. Treatment with 25% EtOH prior to 100% EtOH exposure virtually abolished this injury. In vagotomized animals, 100% EtOH elicited almost three times the amount of injury observed in the nonvagotomized state and the protective effect of 25% EtOH pretreatment was prevented. Effects of the various treatment modalities on GPX and GRT activity were not significantly different from control values. When mucosal GSH results were plotted against the presence or absence of gastric injury among the various groups studied, no significant correlation was apparent. Thus, aberrations in glutathione metabolism do not explain the absence of adaptive cytoprotection following vagotomy or the exacerbation of alcohol-induced damage under conditions of vagal denervation.This work was supported by research grant DK 25838 from the National Institutes of Health. 相似文献
Blood levels of inflammatory-related cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, are
elevated in patients with alcoholic liver diseases. We investigated the effects of these cytokines and ethanol on the expression
of hepatic asialoglycoprotein receptors (AGPRs) in a human hepatoblastoma cell line, HepG2. An [125I]-asialo-orosomucoid binding assay showed significant increases in surface AGPR numbers in HepG2 cells by treatment with
IL-1β, IL-6, and TNF-α, to levels which were approximately 130% of the values in untreated control cells. However, the enhanced
AGPR numbers induced by treatment with these cytokines were markedly suppressed, to 70%–80% of the number in the untreated
cells, by treatment with ethanol. Immunological detection of AGPR with a specific antibody demonstrated that the modulation
of surface AGPR numbers was correlated with the cellular expression levels of AGPR. These results suggest that, although IL-1β,
IL-6, and TNF-α stimulate the synthesis of hepatic AGPR, ethanol suppresses the expression of AGPR augmented by these cytokines.
This leads to an increase in serum asialo-orosomucoid levels caused by the disordered catabolism mediated by AGPR in patients
with alcoholic liver disease.
(Received Dec. 5, 1997; accepted May 22, 1998) 相似文献
Context: Some authors have proposed that post-mortem drug concentrations in bile are useful in estimating concentrations in blood. Both The International Association of Forensic Toxicologists (TIAFT) and the US Federal Aviation Administration recommend that samples of bile should be obtained in some circumstances. Furthermore, standard toxicological texts compare blood and bile concentrations, implying that concentrations in bile are of forensic value.
Aim: To review the evidence on simultaneous measurements of blood and bile drug concentrations reported in the medical literature.
Methods: We made a systematic search of EMBASE 1980–2016 using the search terms (“bile/” OR “exp drug bile level/concentration/”) AND “drug blood level/concentration/”, PubMed 1975–2017 for (“bile[tw]” OR “biliary[tw]”) AND (“concentration[tw]” OR “concentrations[tw]” OR “level[tw]” OR “levels[tw]”) AND “post-mortem[tw]” and also MEDLINE 1990–2016 for information on drugs whose biliary concentrations were mentioned in standard textbooks. The search was limited to human studies without language restrictions. We also examined recent reviews, indexes of relevant journals and citations in Web of Science and Google Scholar. We calculated the bile:blood concentration ratio. The searches together yielded 1031 titles with abstracts. We scanned titles and abstracts for relevance and retrieved 230, of which 161 were considered further. We excluded 49 papers because: the paper reported only one case (30 references); the data referred only to a metabolite (1); the work was published before 1980 (3); the information concerned only samples taken during life (10); or the paper referred to a toxin or unusual recreational drug (5). The remaining 112 papers provided data for analysis, with at least two observations for each of 58 drugs.
Bile:blood concentration ratios: Median bile:blood concentration ratios varied from 0.18 (range 0.058–0.32) for dextromoramide to 520 (range 0.62–43,000) for buprenorphine. Median bile concentrations exceeded blood concentrations by one order of magnitude for several drugs, including dihydrocodeine, quetiapine and sildenafil; and by two orders of magnitude of for buprenorphine, colchicine and 3,4-methylenedioxy-methamphetamine (MDMA), among others. The minimum and maximum values for the ratio differed by a factor of three or more in three-quarters of the cases where data were available and by a factor of 10 or more for over half of the analytes.
Limitations: The data were difficult to find. Medline does not explicitly index the term “drug bile concentration”. It may well be that other reports exist, although they would not alter our major conclusion. Many of the papers that contributed data failed to specify the source of the blood samples or the post-mortem interval, so that no judgment was possible regarding post-mortem redistribution in whole blood or bile.
Conclusions: For most drugs, there are wide ranges of bile:blood concentration ratios, which means that bile and blood concentrations are generally poorly correlated. Bile concentration measurements cannot readily be used to establish post-mortem blood concentrations; nor can they be extrapolated to ante-mortem concentrations. However, because drug concentrations in bile often exceed those in blood, bile may allow qualitative identification of drugs present, even when the blood concentration is below the limit of detection. 相似文献
The effects of hemorrhagic shock, aspirin, and ethanol on the biochemical and morphologic changes of experimental pancreatitis
were evaluated. Pancreatitis was induced by infusing rats with a supramaximally stimulating dose (5 μg/kg/h) of caerulein.
Hemorrhagic shock was established by removing sufficient blood to reduce mean arterial pressure by 30%, where it was maintained
for 30 min. Aspirin (25 mg/kg) and ethanol (2 g/kg) were administered through an orogastric tube at 8-h intervals for 48 h.
Hemorrhagic shock did not alter the degree of hyperamylasemia, pancreatic edema, cathepsin subcellular redistribution, or
in vitro LDH leakage that characterize this model of pancreatitis. Hemorrhagic shock did, however, worsen the morphologic
evidence of pancreatic injury. Administration of aspirin with ethanol did not alter the degree of hyperamy-lasemia, pancreatic
edema, or subcellular cathepsin redistribution. Aspirin-ethanol pretreatment also did not alter the morphologic severity of
pancreatitis. 相似文献
SUMMARY. Patients with primary head and neck cancers have a higher risk of developing esophageal cancer. The aim of this study was to investigate esophageal cancer prevalence, its risk factors (ethanol and tobacco consumption) and dietary habits in patients with head and neck cancer. Three hundred and twenty-six adults with primary head and neck cancer were followed by a retrospective observational study in a general university hospital in Sao Paulo, Brazil. Flexible videoendoscopy with lugol chromoscopy was the method used to investigate esophageal cancer prevalence. All subjects were interviewed face-to-face, revealing detailed information about their tobacco and alcohol use, as well as their dietary habits. Thirty-six patients with esophageal cancer were diagnosed and the overall prevalence rate was 11.04%. Patients who developed second esophageal tumors had the following characteristics: earlier age of initial ethanol consumption ( P < 0.05), longer duration period of ethanol consumption ( P < 0.05) and higher weekly consumption rate ( P < 0.05). There was an increased risk of esophageal carcinoma in those patients who both smoked and drank ( P < 0.05). There was no association between carcinoma of the esophagus and dietary habits in patients who developed esophageal neoplasms, compared with those who did not. Prevalence rate of esophageal neoplasms was 11.04% in patients with head and neck carcinoma, whose ethanol consumption was associated with esophageal cancer. There was an increased risk between ethanol and tobacco consumption and esophageal carcinoma development. On the other hand, there was no association regarding dietary habits between patients who developed esophageal cancer and those who did not. 相似文献
Background. Endogenous and exogenous prostaglandins (PGs) have been shown to contribute to reducing the gastric injury caused by irritants
given subse-quently. The aim of this study was to clarify whether cyclooxygenase-2 (COX-2) protein induced by pretreatment
was involved in the prevention of subsequent ethanol-caused gastric injury in mice. Methods. Mice were pretreated with acidified ethanol or saline and then COX-2 protein expression in the stomach was immunohistochemically
determined every 8 h. Mice were administered 95% ethanol 24 h after the acidified ethanol pretreatment, and gastric mucosal
damage was evaluated macroscopically and histologically. The effects of NS-398 or indomethacin on the 95% ethanol-caused damage
were also examined. Results. Acidified ethanol pretreatment induced COX-2 protein expression in lamina propria macrophages of the gastric mucosa, with
a peak level 24 h after the pretreatment. The 95% ethanol treatment caused gastric mucosal damage. The degree of the damage
was not different between mice pretreated with acidified ethanol and those pretreated with saline. However, NS-398 aggravated
the ethanol-caused damage only in mice pretreated with acidified ethanol, while indomethacin aggravated the damage, evaluated
histologically, irrespective of the pretreatment. Conclusions. Pretreatment-induced COX-2, in addition to COX-1, seemed to be involved in the defense mechanism through minimizing the damage
caused by a subsequent irritant.
Received: October 16, 2000 / Accepted: September 14, 2001 相似文献