UMLS:C0030193 - FACTA Search

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Query: UMLS:C0030193 (pain)
261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Single injections of epinephrine significantly lowered the hepatocellular levels of reduced glutathione (GSH) while producing small but significant elevations in serum glutamic-pyruvic transaminase (SGPT) activity. Hormones, i.e. glucagon and the corticosteroids, were also found to depress significantly hepatic glutathione. Based upon the agonist-antagonist studies performed, the hepatic GSH lowering effects of epinephrine appear to be mediated solely by alpha 2 receptors. Adrenergic antagonists with alpha 2 receptor blocking properties, phenotolamine and yohimbine, prevented the epinephrine-induced lowering of GSH while agonists with alpha 2 activity, clonidine and guanabenz, mimicked epinephrine's response. Antagonists with either alpha 1 or beta activity, i.e. prazosin, phenoxybenzamine and propranolol, did not prevent the epinephrine-induced lowering of hepatic GSH. Contrary to these findings antagonists with either alpha or beta receptor blocking activity significantly reduced the epinephrine-induced elevations in SGPT activity. Thus, there was no apparent relationship between the elevation of SGPT activity and the reduction in hepatic glutathione levels. It is concluded that the therapeutic administration of these compounds, or physiologic responses to stress or pain, may exacerbate the hepatotoxicity of compounds detoxified by GSH or alter important glutathione-mediated hepatocellullar processes.
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PMID:The perturbation of hepatic glutathione by alpha 2-adrenergic agonists. 613 90

Opiates, such as morphine, have been used extensively in the clinical management of pain due to their potent analgesic effect. Astrocytes, representing a major non-neuronal cell population in the CNS, contain opioid receptors that are actively involved in several brain functions. This study was designed to evaluate the effects by which morphine, a preferential mu-opioid receptor agonist, contributes to cytotoxicity of nitric oxide (NO) species, including NO and peroxynitrite (ONOO-), in primary rat neonatal astrocytes. Primary astrocytes isolated from the cerebral cortex of 1- to 2-day-old Sprague-Dawley rats were treated with morphine, naloxone, and 3-morpholinosydnonimine (SIN-1), a donor of peroxynitrite. Morphine significantly protected primary rat astrocytes from apoptosis mediated by sodium nitroprusside, an NO donor, and SIN-1 in a dose-dependent manner, whereas it did not in other types of cells including C6 glioma, RAW 264.7, and HL-60 cells. Moreover, naloxone antagonized the protective effects of morphine on SIN-1-induced apoptosis. Morphine also inhibited the nuclear condensation and fragmentation of SIN-1-treated cells that was antagonized by naloxone pretreatment. The protective role of morphine in SIN-1-induced apoptosis was dependent on an intracellular antioxidant system such as GSH. Furthermore, the effects of morphine on SIN-1-induced cytotoxicity were prohibited by pretreatment with the G(i) protein inhibitor, pertussis toxin, and the phosphatidylinositol 3-kinase (PI3 kinase) inhibitors, wortmannin and LY294002. Taken together, these results suggest that morphine may protect primary rat astrocytes from apoptosis by NO species via the signaling cascades that involve both G protein and PI3 kinase.
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PMID:Protective effects of morphine in peroxynitrite-induced apoptosis of primary rat neonatal astrocytes: potential involvement of G protein and phosphatidylinositol 3-kinase (PI3 kinase). 1127 62

Because the role of elemental sulfur in human nutrition has not been studied extensively, it is the purpose of this article to emphasize the importance of this element in humans and discuss the therapeutic applications of sulfur compounds in medicine. Sulfur is the sixth most abundant macromineral in breast milk and the third most abundant mineral based on percentage of total body weight. The sulfur-containing amino acids (SAAs) are methionine, cysteine, cystine, homocysteine, homocystine, and taurine. Dietary SAA analysis and protein supplementation may be indicated for vegan athletes, children, or patients with HIV, because of an increased risk for SAA deficiency in these groups. Methylsulfonylmethane (MSM), a volatile component in the sulfur cycle, is another source of sulfur found in the human diet. Increases in serum sulfate may explain some of the therapeutic effects of MSM, DMSO, and glucosamine sulfate. Organic sulfur, as SAAs, can be used to increase synthesis of S-adenosylmethionine (SAMe), glutathione (GSH), taurine, and N-acetylcysteine (NAC). MSM may be effective for the treatment of allergy, pain syndromes, athletic injuries, and bladder disorders. Other sulfur compounds such as SAMe, dimethylsulfoxide (DMSO), taurine, glucosamine or chondroitin sulfate, and reduced glutathione may also have clinical applications in the treatment of a number of conditions such as depression, fibromyalgia, arthritis, interstitial cystitis, athletic injuries, congestive heart failure, diabetes, cancer, and AIDS. Dosages, mechanisms of action, and rationales for use are discussed. The low toxicological profiles of these sulfur compounds, combined with promising therapeutic effects, warrant continued human clinical trails.
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PMID:Sulfur in human nutrition and applications in medicine. 1189 44

Capsaicin is a common dietary constituent and a popular homeopathic treatment for chronic pain. Exposure to capsaicin has been shown to cause various dose-dependent acute physiological responses including the sensation of burning and pain, respiratory depression, and death. In this study, the P450-dependent metabolism of capsaicin by recombinant P450 enzymes and hepatic and lung microsomes from various species, including humans, was determined. A combination of LC/MS, LC/MS/MS, and LC/NMR was used to identify several metabolites of capsaicin that were generated by aromatic (M5 and M7) and alkyl hydroxylation (M2 and M3), O-demethylation (M6), N- (M9) and alkyl dehydrogenation (M1 and M4), and an additional ring oxygenation of M9 (M8). Dehydrogenation of capsaicin was a novel metabolic pathway and produced unique macrocyclic, diene, and imide metabolites. Metabolism of capsaicin by microsomes was inhibited by the nonselective P450 inhibitor 1-aminobenzotriazole (1-ABT). Metabolism was catalyzed by CYP1A1, 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4. Addition of GSH (2 mM) to microsomal incubations stimulated the metabolism of capsaicin and trapped several reactive electrophilic intermediates as their GSH adducts. These results suggested that reactive intermediates, which inactivated certain P450 enzymes, were produced during catalytic turnover. Comparison of the rate and types of metabolites produced from capsaicin and its analogue, nonivamide, demonstrated similar pathways in the P450-dependent metabolism of these two capsaicinoids. However, production of the dehydrogenated (M4), macrocyclic (M1), and omega-1-hydroxylated (M3) metabolites was not observed for nonivamide. These differences may be reflective of the mechanism of formation of these metabolites of capsaicin. The role of metabolism in the cytotoxicity of capsaicin and nonivamide was also assessed in cultured lung and liver cells. Lung cells were markedly more sensitive to cytotoxicity by capsaicin and nonivamide. Cytotoxicity was enhanced 5 and 40% for both compounds by 1-ABT in BEAS-2B and HepG2, respectively. These data suggested that metabolism of capsaicinoids by P450 in cells represented a detoxification mechanism (in contrast to bioactivation).
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PMID:Metabolism of capsaicin by cytochrome P450 produces novel dehydrogenated metabolites and decreases cytotoxicity to lung and liver cells. 1264 34

The aim of this study was to compare the in vivo effects on free radical metabolism of 2 non-steroidal anti-inflammatory drugs (NSAIDs): tenoxicam, an oxicam preferentially cyclooxygenase-1 (COX-1) inhibitor, and celecoxib, a sulfonamide selective COX-2 inhibitor. The serum levels of oxidative stress-related enzymes (ie, xanthine oxidase (XO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)), of a lipid peroxidation marker (malondialdehyde (MDA)), and of nitric oxide (NO) in patients with knee osteoarthritis were studied at baseline and after a 4-wk course of treatment with celecoxib (n = 11) and tenoxicam (n = 12). Celecoxib-treated patients had significant decrease in nitrite levels (p = 0.043), whereas SOD, XO, GSH-Px enzyme activities, and MDA levels did not change significantly compared to baseline. Tenoxicam-treated patients had significant decrease in nitrite levels (p = 0.036) and XO activity (p = 0.01), but their SOD, GSH-Px enzyme activities, and MDA levels were unchanged from baseline. There was significant correlation between the patients' (n = 23) Western Ontario and McMaster Universities (WOMAC) LK3.0 Osteoarthritis Index, WOMAC-pain scores, and MDA levels (r = 0.50, p = 0.014) and the patients' WOMAC-stiffness scores and XO enzyme activity (r = 0.46, p = 0.027) at baseline. Significant improvement was found in pain-VAS, patients' global assessment, and WOMAC pain, stiffness, and physical function scores in celecoxib and tenoxicam-treated groups. In summary, our study revealed that tenoxicam may have antioxidant effects, and that celecoxib and tenoxicam may reduce nitrite levels, indicating an alteration of NO pathways.
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PMID:In vivo effect of celecoxib and tenoxicam on oxidant/ anti-oxidant status of patients with knee osteoarthritis. 1594 76

Postoperative intraperitoneal adhesion formation is a major cause of intestinal obstruction, pain and infertility. This experimental study was designed to evaluate the degree of adhesion formation and peritoneal tissue levels of malondialdehyde (MDA), reduced glutathione (GSH) and total nitrite and nitrate (NO) and the effect of aminoguanidine (AG) on these metabolite values after postoperative intraperitoneal adhesion formation in rats. A total of 21 adult male Wistar albino rats were randomly divided into three groups. Control rats were untreated; the AG group received AG 200 mg kg(-1) i.p. for 10 consecutive days intraperitoneally after surgery. The sham group was given 0.9% NaCl. The rats were killed on postoperative day 10. The peritoneal tissues were harvested to determine the tissue levels of MDA, GSH, and NO activity. For light microscopic evaluation, the cecum was removed. Adhesion formation scores in the AG group were significantly lower than those of the control and sham groups (p < 0.017, p < 0.026 respectively). In the AG-treated rats, tissue levels of MDA and NO were significantly lower than in the control group (p < 0.017). The levels of GSH in aminoguanidine-treated rats were significantly higher than those of the control group (p < 0.01). The severity of the inflammation was more prominent in the control group compared with the AG-injected rats. The results demonstrate that in this experimental model, intraperitoneal administration of aminoguanidine decreases the incidence and extent of peritoneal adhesions and causes a decrease in MDA and NO and an increase in GSH values.
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PMID:Protective effect of aminoguanidine against oxidative stress in an experimental peritoneal adhesion model in rats. 1599 Dec 62

Dosing-time-dependent changes in the effect and toxicity of morphine were examined in mice housed under alternating 12 h light (07:00 to 19:00 h) and dark (19:00 to 07:00 h) cycles. Morphine (0.5 mg/kg) was injected intraperitoneally (i.p.) in animals to assess its beneficial effect (i.e., protection against the kaolin-induced, bradykinin-mediated, writhing reaction) and its toxicity (i.e., alteration of the hepatic enzymes of aspartate aminotransferase [AST] alanine aminotransferase [ALT], and glutathione [GSH] in separate experiments). The magnitude of the analgesic effect of morphine depended on dosing time, with minimum effect at 02:00 h and maximum effect at 14:00 h. The serum hepatic enzyme levels of AST and ALT increased after dosing morphine (100 mg/kg) at 02:00 and 14:00 h. Time courses of these enzymes did not differ between the two trials. However, hepatic GSH, which is involved in the detoxification of chemical compounds, significantly decreased after i.p. morphine injection at 02:00 but not at 14:00 h. Overall, the results suggest that the analgesic effect of morphine is greater after dosing during the resting than during the activity phase of mice that have been induced with bradykinin-mediated pain. Drug-induced hepatic damage as inferred by GSH alteration, however, may be greater after dosing during the active phase.
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PMID:Chronopharmacology of morphine in mice. 1607 51

Bis and tris-selenide alkene derivatives, a class of organoselenium compounds, were screened for antinociceptive and antioxidant activities. In vitro, bis-selenide alkene 1c (R=2,4,6-Me(3)C(6)H(2)), 1d (R=4-ClC(6)H(4)) and 1e (R=4-MeOC(6)H(4)) protected against lipid peroxidation about 50%, whereas 1b (R=C(6)H(5)) and 1a (R=C(4)H(9)) protected only 23%. Compound 1d presented lesser IC(50) against lipid peroxidation than other bis-selenide alkene compounds (1d>1e> or =1c>1a=1b). The maximal inhibitory effect of tris-selenide alkenes on lipid peroxidation was in the following order 2c>2a=2b. Compound 1e increased the rate of GSH, but not DTT, oxidation. Tris-selenide alkene 2c (R=4-MeOC(6)H(4)) demonstrated the higher rate of thiol oxidation, while 2a (R=C(6)H(5)) did not change DTT oxidation but oxidized GSH. Conversely, compound 2b (R=4-ClC(6)H(4)) did not change the rate of GSH oxidation, but oxidized DDT. Bis-selenide alkene derivatives 1c, 1d and 1e were the most promising compounds tested in vitro. In vivo, compounds 1c and 1d (5-50mg/kg, subcutaneously) produced significant inhibition of acetic acid- and capsaicin-induced pain. Compounds 1c and 1d increased the tail-flick response latency time. The antinociception effect of 1c and 1d was not abolished by naloxone (an antagonist of opioid receptor, 1mg/kg, subcutaneously), suggesting that the antinociceptive effect is not influenced by the opioidergic mechanism.
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PMID:Bis selenide alkene derivatives: A class of potential antioxidant and antinociceptive agents. 1654 42

In this study we assessed activities of antioxidant enzymes, lipid peroxidation end-products, and nitric oxide (NO) levels in women with postmenopausal osteoporosis (PMO). Relationship between oxidative stress parameters and NO levels with bone mineral density (BMD) and clinical variables influencing bone mass and health related quality of life measures was also investigated in women with PMO. Postmenopausal women (n=87), aged 40-65, without previous diagnosis or treatment for osteoporosis and independent in daily living activities were included. BMD was measured at the lumbar spine and proximal femur using dual-X-ray absorptiometry (DXA). Erythrocyte catalase (CATe) enzyme activity, erythrocyte and plasma enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and lipid peroxidation end-product malondialdehyde (MDA) and nitrite/nitrate levels, by product of NO were studied. A total of 23 healthy non-porotic women were included as controls. Women with PMO had significantly lower erythrocyte CATe enzyme activity and higher erythrocyte malondialdehyde (MDAe) and erythrocyte nitric oxide (NOe) levels in comparison to controls whereas erythrocyte SODe and GSH-Px enzyme activity was similar. In plasma, osteoporotic women had significantly higher SOD enzyme activity and higher MDA levels whereas similar GSH-Px enzyme activity and NO levels compared to non-porotic controls. Significant correlation was found between erythrocyte SODe, CATe enzyme activity and NOe levels with proximal femur BMD. Some of the quality of life scores as pain, mental, and social functions correlated with antioxidant enzyme activities and NO levels.Consequently, oxidative stress markers may be an important indicator for bone loss in postmenopausal women. Further researches assessing the oxidative stress markers and NO in bone tissue and changes with anti-osteoporotic drugs would be valuable to better understand the role of free radicals, antioxidants, and NO in the regulation of bone mass.
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PMID:Role of antioxidant systems, lipid peroxidation, and nitric oxide in postmenopausal osteoporosis. 1684 Nov 80

The root of Aralia continentalis Kitagawa has been used in traditional Korean medicine to relieve pain and to treat inflammation. The purpose of this study was to investigate the protective effects of the extract of A. continentalis roots (AC) against hepatotoxicity induced by carbon tetrachloride (CCl4) and the mechanism of its hepatoprotective effect. In mice, pretreatment with AC prior to the administration of CCl4 significantly prevented the increased serum enzymatic activity of ALT and AST as well as the formation of hepatic malondialdehyde. Histopathological evaluation of the livers also revealed that AC reduced the incidence of liver lesions induced by CCl4. In addition, pretreatment with AC significantly prevented both the depletion of reduced glutathione (GSH) content and the decrease in glutathione-S-transferase (GST) activity in the liver of CCl4-intoxicated mice. Hepatic GSH levels and GST activity were increased by treatment with AC alone. Heme oxygenase-1 (HO-1) is known to be induced by oxidative stress and to confer protection against oxidative tissue injuries. Interestingly, AC markedly upregulated hepatic HO-1 expression in CCl4-treated mice, which might provide anti-oxidative activity in the liver. These results indicate that AC plays a critical protective role in CCl4-induced acute liver injury by promoting anti-oxidative protein expression.
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PMID:Protective effect of the Aralia continentalis root extract against carbon tetrachloride-induced hepatotoxicity in mice. 1898 26

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