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Protection Against Chemically-Induced Oxidative Gastrointestinal Tissue Injury in Rats by Bismuth Salts 总被引:1,自引:0,他引:1
Debasis Bagchi Owen R. Carryl Minh X. Tran Manashi Bagchi Phillip J. Vuchetich Roger L. Krohn Siddhartha D. Ray Sekhar Mitra Sidney J. Stohs 《Digestive diseases and sciences》1997,42(9):1890-1900
Oxygen free radicals (OFR) are implicated in thepathogenesis of stress, chemically induced gastriclesions, and gastrointestinal injury. Theconcentration-dependent scavenging abilities of bismuthsubsalicylate (SBS), colloidal bismuth subcitrate (CBS), andselected OFR scavengers, including superoxide dismutase(SOD), catalase, mannitol, and allopurinol were examinedagainst biochemically or chemically generated superoxide anion, hydroxyl radical, andhypochlorite radical plus hypochlorous acid based on achemiluminescence assay. Furthermore, both gastric (GM)and intestinal mucosa (IM) were individually exposed in vitro to these free radical generatingsystems, and the concentration-dependent protectiveabilities of SBS and CBS against lipid peroxidation (LP)were compared with selected OFR scavengers. In addition, 24-hr fasted rats were orally treated with thenecrotizing agents 0.6 M HCl, 0.2 M NaOH, 80% ethanol,and aspirin (200 mg/kg). The extent of tissue injury inthe GM and IM was determined by assessing LP, DNA fragmentation, and membrane microviscosity.Dose- and time-dependent in vivo protective abilities ofCBS (100 mg/kg) and SBS (15 mg/kg) were also assessed.Following incubations with superoxide anion and hydroxyl radical generating systems in thepresence of 125 mg SBS/liter, approximately 47% and 61%inhibitions were observed in the chemiluminescenceresponse, respectively, while 48% and 46% inhibitions were observed with 125 mg CBS/liter. SBS andCBS exerted similar abilities towards hypochloriteradical plus hypochlorous acid. Approx. 3.1- and3.7-fold increases in LP were observed in the GM and IMof rats following oral administration of 0.6 MHCl. Pretreatment of the rats with SBS and CBS decreased0.6 M HCl-induced LP in the GM by approx. 39% and 27%,respectively, with similar decreases in LP in the IM. SBS exhibited better protectiveabilities towards 0.6 M HCl and 0.2 m NaOH-induced GMand IM injury as compared to CBS. SBS and CBS providedsimilar protection towards 80% ethanol-induced gastric injury, while CBS exerted a superior protectiveability towards aspirin-induced gastric injury. Theresults demonstrate that both SBS and CBS can scavengereactive oxygen species and prevent tissue damage produced by OFR. 相似文献
44.
D T Baran A M Sorensen T W Honeyman R Ray M F Holick 《Journal of bone and mineral research》1990,5(5):517-524
1 alpha,25-Dihydroxyvitamin D3 rapidly increases cytosolic calcium and alters membrane phospholipid metabolism in hepatocytes. To define the causal relationship between these events, we examined the effects of 1 alpha,25-dihydroxyvitamin D3 on 32P-labeled lysophosphatidylinositol levels and cytosolic calcium as affected by pertussis toxin and 1 beta,25-dihydroxyvitamin D3, the biologically inactive analog. 32P-labeled lysophosphatidylinositol was determined by two-dimensional thin-layer chromatography. Cytosolic calcium was measured in cells loaded with quin-2AM. Within 5 min, 1 alpha,25-dihydroxyvitamin D3 increased hepatocyte cytosolic calcium by 31% (p less than 0.05) and 32P-labeled lysophosphatidylinositol by 38% (p less than 0.05). Pertussis toxin inhibited the hormone-induced rise in cytosolic calcium but not the increase in 32P-labeled lysophosphatidylinositol. Exposure to exogenous lysophosphatidylinositol for 5 min increased cytosolic calcium by 40% (p less than 0.05), an effect that was also inhibited by pertussis toxin. 1 beta,25-Dihydroxyvitamin D3 had no effect on either hepatocyte cytosolic calcium or 32P-labeled lysophosphatidylinositol but prevented the 1 alpha,25-dihydroxyvitamin D3-induced increments. The results suggest that a G protein sensitive to pertussis toxin is required for the transduction of the lysophosphatidylinositol signal but not the generation of the signal. The ability of 1 beta,25-dihydroxyvitamin D3 to inhibit the 1 alpha,25-dihydroxyvitamin D3-induced changes in phospholipids suggests that the epimer may compete with 1 alpha,25-dihydroxyvitamin D3 for an initiating receptor. 相似文献
45.
Wong Joseph Kuu Wei-Youh Burke Ronald Johnson Robert Wood Ray W. 《Pharmaceutical research》1995,12(1):144-148
The primary objective of this work was to establish a method to simulate the plasma levels of cilastatin, a model drug, following an intravenous in-line delivery scheme. In-vivo data in dogs obtained from this work were used to demonstrate the validity of the proposed approach. The in-line drug delivery system consists of a drug containing device which is placed between a large volume parenteral and a patient. Numerous advantages have been identified for this automatic in-line reconstitution delivery system. The numerical convolution integral algorithm was used in this work to perform plasma profile simulation. The results indicated that the simulated cilastatin plasma profile following in-line delivery closely agreed with the in-vivo data. 相似文献
46.
Protection against 7,12-dimethylbenzanthracene-induced tumour initiation by protein A in mouse skin.
S Kumar Y Shukla A K Prasad A S Verma P D Dwivedi N K Mehrotra P K Ray 《Cancer letters》1992,61(2):105-110
Protein A is an immunostimulating glycoprotein obtained from Staphylococcus aureus Cowan I. Its antitumour activity is proven in various tumour models. Its ability to provide protection against tumour initiation by the chemical carcinogen 7,12-dimethylbenzanthracene (DMBA) has been investigated in the present study using a mouse skin model of two-stage carcinogenesis. Protein A was administered intraperitoneally (1 microgram/animal 20 g body wt.) twice a week for 2 weeks, prior to initiation by DMBA. The promotion was performed by twice weekly applications of 12-O-tetradecanoyl phorbol-13-acetate (TPA) (3 or 5 micrograms/animal in 100 microliters acetone). Protein A provided significant protection to animals from DMBA-induced tumour initiation as was observed by the decrease in cumulative number of tumours, percent of animals developing tumours, number of tumours per animal and rate of tumour growth. Our data indicate that protein A has anticarcinogenic properties. 相似文献
47.
AR Jones BSC AJP Sandison FRCS WJ Owen MS FRCS 《International journal of clinical practice》1997,51(5):294-295
Pre-clerking of all patients undergoing elective general surgical operations was introduced at our hospital in an attempt to reduce an unacceptably high operation cancellation rate. A prospective audit has been performed on the effect of this policy on the cancellation rate. Before the introduction of pre-clerking there was a marked seasonal variation in the number of patients who failed to attend for surgery, which could be explained by absence on holiday. This seasonal variation disappeared after the start of pre-clerking clinics, but there has been no reduction in the number of cancellations for medical reasons. 相似文献
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C S Degoute F Gilly M Manchon P Chatelard M J Ray V Banssillon 《International surgery》1990,75(4):234-237
This prospective study was designed to test the hypothesis that intraoperative hypothermia occurring during abdominal aortic surgery and vasodilator therapy used to avoid severe consequences of aortic clamping could both disturb the mixed venous oxygen saturation signal (SVO2). Twenty high risk surgical patients, ASA physical status II or III, were catheterized with the standard pulmonary artery catheter; SVO2 was determined by direct spectrophotometric measurements of oxygen haemoglobin concentration of serial samples. The relationships between SVO2, haemodynamic, metabolic variables and core temperature were analyzed. Haemodynamic values and oxygen transport were stable while inadequate tissue oxygenation occurred. A significant correlation was found between SVO2 and CI (r = 0.59, p less than 0.01), SVO2 and SVRI (r = -0.4, p less than 0.01), SVO2 and CT (r = -0.46, p less than 0.01), SVO2 and VO2 (r = -0.76, p less than 0.001). SVO2 and Qs/Qt (r = 0.83, p less than 0.001), SVO2 and EO2 (r = -0.75, p less than 0.001. No correlation was observed between SVO2 and lactacidemia (r = 0.04, p less than 0.05). Satisfactory haemodynamic stability and oxygen transport steady-state were the main conditions for a significant correlation between SVO2 and haemodynamic factors. However, there was no correlation between SVO2 and inadequate tissue oxygenation. SVO2 reflected only oxygen extraction. Intraoperative hypothermia provided an increased haemoglobin affinity for oxygen. Vasodilator therapy which allowed a decrease in systemic vascular resistance produced an increase in the left-right shunt and in venous oxygen admission. Thus hypothermia and vasodilator therapy could be both responsible for the elevated SVO2 occurring during infrarenal abdominal aortic surgery. 相似文献