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21.
Liver and kidney toxicity in chronic use of opioids: An experimental long term treatment model 总被引:2,自引:0,他引:2
In this study, histopathological and biochemical changes due to chronic usage of morphine or tramadol in liver and kidney
were assessed in rats. Thirty male Wistar rats (180–220 g) were included and divided into three groups. Normal saline (1 ml)
was given intraperitoneally as placebo in the control group (n = 10). Morphine group (n = 10) received morphine intraperitoneally at a dose of 4, 8, 10 mg/kg/day in the first, second and the third ten days of
the study, respectively. Tramadol group (n = 10), received the drug intraperitoneally at doses of 20, 40 and 80 mg/kg/day in the first, second and the third ten days
of the study, respectively. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH),
creatinin, blood urea nitrogen (BUN) and malondialdehyde (MDA) levels were measured in the serum. Liver and kidney specimens
were evaluated by light microscopy. Serum ALT, AST, LDH, BUN and creatinin levels were significantly higher in morphine group
compared to the control group. Serum LDH, BUN and creatinin levels were significantly increased in the morphine group compared
to the tramadol group. The mean MDA level was significantly higher in morphine group compared to the tramadol and control
groups (P<0.05). Light microscopy revealed severe centrolobular congestion and focal necrosis in the liver of morphine and
tramadol groups, but perivenular necrosis was present only in the morphine group. The main histopathologic finding was vacuolization
in tubular cells in morphine and tramadol groups. Our findings pointed out the risk of increased lipid peroxidation, hepatic
and renal damage due to long term use of opioids, especially morphine. Although opioids are reported to be effective in pain
management, their toxic effects should be kept in mind during chronic usage
Presented at the 10th XX Annual ESRA Congress, 6–9 April 2002, Warsaw, Poland. 相似文献
22.
In this work, the inhibitory effect of some symmetric sulfamides derived from phenethylamines were determined against human carbonic anhydrase (hCA) I, and II isoenzymes, and compared with standard compound acetazolamide. IC50 values were obtained from the Enzyme activity (%)-[Symmetric sulfamides] graphs. Also, Ki values were calculated from the Lineweaver-Burk graphs. Some symmetric sulfamides compounds ( 11 – 18 ) demonstrated excellent inhibition effects against hCA I, and II isoenzymes. These compounds demonstrated effective inhibitory profiles with IC50 values in ranging from 21.66–28.88 nM against hCA I, 14.44–30.13 nM against hCA II. Among these compounds, the best Ki value for hCA I (Ki: 8.34±1.60 nM) and hCA II (Ki: 16.40±1.00 nM) is compound number 11 . Besides, the IC50 value of acetazolamide used as a standard was determined as hCA I, hCA II 57.75 nM, 49.50 nM, respectively. Moreover, in silico ADME-Tox study showed that all synthesized compounds ( 11 – 18 ) had good oral bioavailability in light of Jorgensen's rule of three, and of Lipinski's rule of five. 相似文献
23.
Pekkurnaz G Fera A Zimmerberg-Helms J Degiorgis JA Bezrukov L Blank PS Mazar J Reese TS Zimmerberg J 《The Biological bulletin》2011,220(2):89-96
Synaptic vesicles contain a variety of proteins and lipids that mediate fusion with the pre-synaptic membrane. Although the structures of many synaptic vesicle proteins are known, an overall picture of how they are organized at the vesicle surface is lacking. In this paper, we describe a better method for the isolation of squid synaptic vesicles and characterize the results. For highly pure and intact synaptic vesicles from squid optic lobe, glycerol density gradient centrifugation was the key step. Different electron microscopic methods show that vesicle membrane surfaces are largely covered with structures corresponding to surface proteins. Each vesicle contains several stalked globular structures that extend from the vesicle surface and are consistent with the V-ATPase. BLAST search of a library of squid expressed sequence tags identifies 10 V-ATPase subunits, which are expressed in the squid stellate ganglia. Negative-stain tomography demonstrates directly that vesicles flatten during the drying step of negative staining, and furthermore shows details of individual vesicles and other proteins at the vesicle surface. 相似文献
24.
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25.
PRAS40 has recently been identified as a protein that couples insulin/IGF signaling (IIS) to TORC1 activation in cell culture; however, the physiological function of PRAS40 is not known. In this study, we investigate flies lacking PRAS40. Surprisingly, we find both biochemically and genetically that PRAS40 couples IIS to TORC1 activation in a tissue-specific manner, regulating TORC1 activity in ovaries but not in other tissues of the animal. PRAS40 thereby regulates fertility but not growth of the fly, allowing distinct physiological functions of TORC1 to be uncoupled. We also show that the main function of PRAS40 in vivo is to regulate TORC1 activity, and not to act as a downstream target and effector of TORC1. Finally, this work sheds some light on the question of whether TORC1 activity is coupled to IIS in vivo. 相似文献
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Kucukatay V Turgut S Kocamaz E Emmungil G Bor-Kucukatay M Turgut G Akca H Bagci H 《Biological trace element research》2006,114(1-3):185-195
Sulfite is a potentially toxic molecule that might enter the body via ingestion, inhalation, or injection. For cellular detoxification,
mammalians rely on sulfite oxidase to convert sulfite to sulfate. The purpose of this research was to determine the effect
of sulfite on zinc, iron, and copper levels in rat liver and kidney tissues. Forty normal and sulfite oxidase-deficient male
albino rats were divided into four groups that included untreated controls (group C), a sulfite-supplemented group that received
70 mg sodium metabisulfite per kilogram per day (group S), a sulfite oxidase-deficient group (group D), and a sulfite oxidase-deficient
group that was also given 70 mg sodium metabisulfite per kilogram per day (group DS). The iron and zinc levels in the liver
and kidney in groups S and DS were not affected by sulfite treatment compared to their respective controls (groups C and D).
Sulfite exposure led to an increase of kidney copper content in the S group when compared to untreated controls. The kidney
copper levels were significantly increased in the unexposed deficient rats, but it was not different than that of the deficient
rats that were given oral sulfite treatment. These results suggest that kidney copper levels might be affected by exogenous
or endogenous sulfite.
An erratum to this article is available at . 相似文献
28.
Halise Inci Gul Cem Yamali Fatma Yesilyurt Hiroshi Sakagami Kaan Kucukoglu Ilhami Gulcin 《Journal of enzyme inhibition and medicinal chemistry》2017,32(1):369-374
In this study, 4-[5-(4-hydroxyphenyl)-3-aryl-4,5-dihydro-1H-pyrazol-1-yl]benzenesulfonamide derivatives (8-14) were synthesized for the first time by microwave irradiation and their chemical structures were confirmed by 1H NMR, 13C NMR and HRMS. Cytotoxic activities and inhibitory effects on carbonic anhydrase I and II isoenzymes of the compounds were investigated. The compounds 9 (PSE?=?4.2), 12 (PSE?=?4.1) and 13 (PSE?=?3.9) with the highest potency selectivity expression (PSE) values in cytotoxicity experiments and the compounds 13 (Ki?=?3.73?±?0.91?nM toward hCA I) and 14 (Ki?=?3.85?±?0.57?nM toward hCA II) with the lowest Ki values in CA inhibition studies can be considered as leader compounds for further studies. 相似文献
29.
Hatice Yorulmaz Elif Ozkok Gulten Ates Abdullah Aksu Nuray Balkıs Sule Tamer 《International journal of peptide research and therapeutics》2018,24(2):259-264
We investigated the effects of exogenous ghrelin on energy levels and tissue histology in skeletal muscle in experimentally lipopolysaccharide (LPS) induced septic rats. Male Wistar albino rats 200–250 g were separated into four groups; Control, LPS (5 mg/kg), Ghrelin (10 nmol/kg i.v.), and ghrelin+LPS. Gastrocnemius muscle tissue was taken and stained using modified Gomori trichrome (MGT), succinic dehydrogenase (SDH), and cytochrome oxidase (COX) and hematoxylin and eosin. In stained sections, histological score value was calculated according to the intensity and the distribution for MGT, SDH and COX stainings. Creatine, creatine phosphate, adenosine triphosphate (ATP), adenosine monophosphate (AMP) levels, and the ratios of AMP/ATP and CreaP/ATP were investigated using high performance liquid chromatography (HPLC) in muscle tissue. Significances between experimental groups were calculated with an analysis of variance (ANOVA) followed by Tukey’s tests. Myopathic changes were seen in the 50% of rats in the LPS group as rounding of muscle fibers and fiber size variation. In the ghrelin+LPS group, ghrelin treatment was reduced damage in skeletal muscle structure. There was no change in creatine or AMP levels between the groups. Ghrelin treatment significantly increased ATP values (P?<?0.01) and improved tissue histology in septic rats. Ratios of both AMP/ATP and CreaP/ATP were found increased in the septic group, but there were decreaments in both the ghrelin and ghrelin-treated septic groups. Ghrelin could play an important role in energy balance and muscle morphology in skeletal muscle during sepsis. 相似文献
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