1.Prostaglandin E in rabbit aqueous humor after Nd-YAG laser photodisruption of the iris and the effect of topical indomethacin pretreatment.
Chun Ki JOO ; Man Soo KIM ; Jae Ho KIM
Korean Journal of Ophthalmology 1987;1(2):122-127
Rabbit eyes were irradiated with a neodymium-yttrium-aluminum-garnet (Nd-YAG) laser and the changes in prostaglandin E and protein levels in the aqueous humor were measured. Intraocular pressure and pupil diameter were also determined in the same rabbits. Prostaglandin E and protein in the aqueous humor were increased depending upon the number of laser lesions. The increase in intraorular pressure and the decrease in pupil diameter occurred at similar dosages of laser irradiation. The response of the iris to the photodisruption was rapid. Changes in prostaglandin and protein contents and pupil diameter were already prominent 15 min after laser irradiation. Indomethacin pretreatment abolished most of these responses, suggesting that acute reactions following photodisruption were largely dependent on prostaglandin synthesis in iris tissue
Administration, Topical
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Animals
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Aqueous Humor/*analysis
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Female
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Indomethacin/*pharmacology
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Iris/*surgery
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Laser Therapy
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*Light Coagulation
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Male
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Prostaglandins E/*analysis
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Rabbits
2.The role of cyclooxygenase-2/prostanoid pathway in visceral pain induced liver stress response in rats.
Donald PISTON ; Shan WANG ; Yi FENG ; Ying-jiang YE ; Jing ZHOU ; Ke-wei JIANG ; Feng XU ; Yong ZHAO ; Zhi-rong CUI
Chinese Medical Journal 2007;120(20):1813-1819
BACKGROUNDCyclooxygenase (COX) is the rate-limiting enzyme in the production of prostanoids from arachidonic acid. COX-2 is the inducible enzyme in the COX family, together with the prostanoids forms the COX-2/prostanoid pathway. Research showed that the COX-2/prostanoid pathway is activated in hepatic diseases and liver stress reaction, such as fibrogenesis, portal hypertension, carcinogenesis, and ischemic/reperfusion injury. But there was no report on visceral pain induced liver stress. This study was to investigate the role of the COX-2/prostanoid pathway in liver stress response in rat acute colitis visceral pain liver stress model.
METHODSFifty-three male SD rats were randomly divided into Naive, Model, NS398 treatment, and Morphine treatment groups. The rat acute colitis visceral pain liver stress model was established under anesthesia by the colonic administration of 0.5 ml of 6% acetic acid using a urethral catheter. NS398 and morphine were administrated 30 minutes prior to model establishment in NS398 and Morphine treatment groups respectively. Spontaneous activities and pain behavior were counted and the extent of colonic inflammation was assessed histologically. Liver tissue levels of Glutathione-S-Transferase (GST) activity, COX-2 mRNA, prostaglandin E2 (PGE2), thromboxane B2 (TXB2) and 6-Ketone-prostaglandin F1alpha (6-K-PGF1alpha) contents were assessed.
RESULTSThirty minutes after the colonic administration of acetic acid, a significant decrease in spontaneous activities and an increase in pain behaviors were observed in Model group (P < 0.01 and P < 0.05 respectively), accompanied by colonic inflammation. Liver GST activity levels significantly dropped (P < 0.05). Liver COX-2 mRNA expression significantly increased, accompanied by an increase in liver concentrations of PGE2 and TXB2, but no obvious change in 6-K-PGF1alpha concentrations. NS398 and morphine both ameliorated post-stress liver GST activity (P < 0.05 and P < 0.01 respectively), decreased stress-induced COX-2 expression, decreased PGE2 and TXB2 production, but increased liver 6-K-PGF1alpha levels. Morphine attenuation in colonic tissue inflammation was apparent at 24 hours (P < 0.05).
CONCLUSIONSAcute colitis visceral pain liver stress can induce liver injury. Liver injury might have occurred through the activation of the COX-2/prostanoid pathway and increased production of PGE2 and TXB2. Effective analgesia might offer protective effect during visceral pain stress.
Acute Disease ; Animals ; Colitis ; physiopathology ; Cyclooxygenase 2 ; physiology ; Hyperalgesia ; physiopathology ; Liver ; metabolism ; Liver Diseases ; physiopathology ; Male ; Morphine ; pharmacology ; Nitrobenzenes ; pharmacology ; Prostaglandins ; physiology ; Rats ; Rats, Sprague-Dawley ; Sulfonamides ; pharmacology
3.Effects of ATP-sensitive potassium channel opener iptakalim against ventricular remodeling and its mechanisms of endothelial protection.
Ming-Li ZHONG ; Hui WANG ; Hong-Min ZHOU ; Yan-Fang ZHANG ; Wen-Yu CUI ; Chao-Liang LONG ; Lian DUAN ; Hai WANG
Chinese Journal of Applied Physiology 2013;29(3):205-208
OBJECTIVETo study the effects of iptakalim (Ipt), an ATP-sensitive potassium channel opener, on cardiac remodeling induced by isoproterenol (ISO) in Wistar rats.
METHODSISO was given subcutaneously (85 mg/(kg x d), sc, 7 days) to induce cardiac remodeling in rats. The rats in Ipt treated group were administrated with Ipt 3 mg/kg (po) after ISO injection. After treated with Ipt for 6 weeks, the hemodynamic parameters were tested by an eight channel physiological recorder (RM-6000). Then the heart weight was weighed and the cardiac remodeling index was calculated. HE stain and Masson's stain were employed to perform histological analysis, the hydroxyproline(Hyp) content in cardiac tissue was detected by colorimetric method, radioimmunoassay was used to measure the plasma levels of endothelin-1 (ET-1) and prostacyclin (PGI2).
RESULTSSix weeks after ISO injection, the cardiac functions of model group were damaged markedly compared with those of normal group. The characteristics of ventricular remodeling in model group included that the heart weight index, myocyte cross-sectional area, myocardial fibrosis, and the hydroxyproline content in cardiac tissue were all increased significantly. The plasma level of ET-1 was increased, while the plasma level of PGI2 was decreased significantly. These changes could be reversed by Ipt treatment (3 mg/(kg x d) for 6 weeks).
CONCLUSIONIpt can reverse cardiac remodeling induced by isoproterenol in rats. The endothelial protective effect regulating effects of Ipt on the balance between the ET-1 and PGI2 system may be involved in its mechanisms.
Animals ; Endothelin-1 ; blood ; Hemodynamics ; Hydroxyproline ; metabolism ; Isoproterenol ; pharmacology ; KATP Channels ; drug effects ; Male ; Myocardium ; metabolism ; Propylamines ; pharmacology ; Prostaglandins I ; blood ; Rats ; Rats, Wistar ; Ventricular Remodeling ; drug effects
4.In Vitro Effects of Preservative-free and Preserved Prostaglandin Analogs on Primary Cultured Human Conjunctival Fibroblast Cells.
Eun Joo KIM ; Yeoun Hee KIM ; Sun Hee KANG ; Kyoo Won LEE ; Young Jeung PARK
Korean Journal of Ophthalmology 2013;27(6):446-453
PURPOSE: Long-term use of topical medication is needed for glaucoma treatment. One of the most commonly prescribed classes of hypotensive agents are prostaglandin analogs (PGs) used as both first-line monotherapy; as well as in combination therapy with other hypotensive agents. Several side effects of eye drops can be caused by preservatives. The purpose of this study was to evaluate the effects of PGs with varying concentrations of benzalkonium chloride (BAC), alternative preservatives, or no preservatives on human conjunctival fibroblast cells. METHODS: Primary human conjunctival fibroblast cells were used in these experiments. Cells were exposed to the following drugs: BAC at different concentrations, bimatoprost 0.01% (with BAC 0.02%), latanoprost 0.005% (with BAC 0.02%), tafluprost 0.0015% with/without 0.001% BAC and travoprost 0.004% (with 0.001% Polyquad) for 15 and 30 minutes. Cell cytotoxicity was evaluated by phase-contrast microscopy to monitor morphological changes of cells, Counting Kit-8 (CCK-8) assay to cell viability, and fluorescent activated cell sorting (FACS) analysis to measure apoptosis. RESULTS: BAC caused cell shrinkage and detachment from the plate in a dose-dependent manner. Morphological changes were observed in cells treated with bimatoprost 0.01% and latanoprost 0.005%. However, mild cell shrinkage was noted in cells treated with tafluprost 0.0015%, while a non-toxic effect was noted with travoprost 0.004% and preservative-free tafluprost 0.0015%. CCK-8 assay and FACS analysis showed all groups had a significantly decreased cell viability and higher apoptosis rate compared with the control group. However, travoprost 0.004% and preservative-free tafluprost 0.0015% showed lower cytotoxicity and apoptosis rate than other drugs. CONCLUSIONS: This in vitro study revealed that BAC-induced cytotoxicity is dose-dependent, although it is important to emphasize that the clinical significance of toxicity differences observed among the different PGs formulations has not yet been firmly established. Alternatively preserved or preservative-free glaucoma medications seem to be a reasonable and viable alternative to those preserved with BAC.
Apoptosis
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Cell Line
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Cell Survival/drug effects
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Conjunctiva/drug effects/*pathology
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Fibroblasts/drug effects/pathology
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Glaucoma/drug therapy/pathology
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Humans
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Preservatives, Pharmaceutical/*pharmacology
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Prostaglandins, Synthetic/*pharmacology
5.Study on analgesic and accompanying toxic and side effects of euodiae fructus based on clinical efficacy dose.
China Journal of Chinese Materia Medica 2013;38(13):2176-2181
OBJECTIVETo observe and study the toxic and side effects of water extracts from Euodiae Fructus accompanied with its efficacy analgesic dose and its mechanism, in order to provide experimental basis for the correlation between its "efficacy-toxicity".
METHODMice were randomly divided into 5 groups according to weight, namely the normal group, the voltaren group, and Euodiae Fructus water extracts high, middle and low dose groups. Mice were administered with drugs for consecutively seven days, abdominally injected with acetic acid at 90 min and treated with hot plates after the last administration to establish the pain model, in order to the toxic and side effects accompanied with the efficacy. Besides toxic symptoms in mice, activities of ALT and AST, and content of BUN and Cr in serum were detected to calculate indexes in livers and kidneys. The other part of serum was collected to detect the content and activities of PGE2, MDA, SOD, NO, NOS, GSH and GSH-PX in serum.
RESULTContinuous oral administration of water extracts from Euodiae Fructus of efficacy dose could significantly decrease the frequency of writhe in mice and increase the hot plate pain threshold, with good dose-efficacy relationship. During the administration, mice showed such toxic symptoms as diarrhoea, idle move, dysphoria and slow growth of weight. The activities of both ALT and AST in serum and hepatic tissues were remarkably increased and the liver size remarkably increased, without notable chance in content of BUN and CR in serum. Kidney size increased in only the high dose group. The content and activities of PGE2, SOD, GSH, GSH-PX in serum notably decreased, where the content and activities of MDA, NO, NOS in serum increased. The above-mentioned changes gradually aggravated with the rise in dose. There was significant difference compared with the model group, showing 'dose-toxicity' relationship to certain extent.
CONCLUSIONContinuous oral administration of certain dose of water extracts from Euodiae Fructus to mice can generate the toxic and side effects in liver accompanying with the analgesic effect, and show dose-dependence relationship to some extent. Its analgesic mechanism is related to the reduction of PGE, content in blood, while its toxic mechanism is related to oxidative injury to some extent.
Analgesics ; pharmacology ; toxicity ; Animals ; Dose-Response Relationship, Drug ; Evodia ; Female ; Kidney ; drug effects ; Liver ; drug effects ; Male ; Mice ; Oxidative Stress ; Plant Extracts ; pharmacology ; toxicity ; Prostaglandins E ; blood
6.Nonsteroidal Anti-inflammatory Drugs.
Yeungnam University Journal of Medicine 2000;17(1):1-11
Inhibition of cyclooxygenase(COX), and thus prevention of the formation of prostaglandins, provided a unifying explanation of the therapeutic and toxic actions of nonsteroidal anti-inflammatory drugs(NSAIDs). Recently, the discovery of the two isoforms of COX was made by molecular biologists studying neoplastic transformation in chick embryo cells. The constitutive enzyme, COX-1, is obviously responsible for the production of prostaglandins involved in housekeeping functions such as maintenance of integrity of the gastric mucosa, renal blood flow and platelet aggregation. The inducible form of COX(COX-2) is responsible for the formation of prostaglandins that pathologic effects of inflammation, pain and fever. Clearly, all the experimental and clinical data support the hypothesis that the beneficial effects of NSAIDs are due to inhibition of the COX-2 enzyme, whereas the gastrotoxicity is due to inhibition of COX-1. The COX-2/COX-1 ratios of the NSAIDs in common use have been measured and compared with epidemiological data on their side effects. there is little evidence to suggest that one NSAID is clearly more efficacious than another and substantial individual variability is present with respect to the pharmacology and pharmacokinetics of these drugs, it is essential to adjust the dosage and choose specific drug to the patient`s response.
Animals
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Anti-Inflammatory Agents, Non-Steroidal
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Chick Embryo
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Fever
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Gastric Mucosa
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Housekeeping
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Inflammation
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Pharmacokinetics
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Pharmacology
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Platelet Aggregation
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Prostaglandins
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Protein Isoforms
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Renal Circulation
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Toxic Actions
7.Effects of prostaglandins on ethanol damage in primary cultured rat hepatocytes.
Jin Mo YANG ; Sang Wook CHOI ; Sung Soo KIM ; Hee Sik SUN ; Doo Ho PARK ; Sang Bae HAN ; Goo Taeg OH ; Whan Mook KIM
The Korean Journal of Internal Medicine 1998;13(1):1-9
OBJECTIVES: Several reports demonstrated that ethanol administration impairs the DNA synthesis in rat hepatocytes. Also, it has been demonstrated that prostaglandin (PG) helps prevent membrane damage by hepatotoxic chemicals. In this study, the authors examined PG's effects on the toxicity of ethanol in the primary culture of rat regenerations. METHODS: We examined two kinds of parameters, i.e., DNA synthesis and lipid peroxidation in the primary culture of rat hepatocytes. Hepatocytes were isolated by the collagenase perfusion method. The rate of DNA synthesis was determined by pulse-labelling cultured cells with [3H]-thymidine. Incorporation of (3H)-thymidine was determined by liquid scintillation spectrophotometer. DNA content was measured by the fluorescence spectrophotometer. The lipid peroxidation was assayed with spectrophotometer. RESULTS: The results were as follows: 1) PG family (PGA1, PGD2, PGE1, PGE2, PGG2a, PGI2 & Thromboxane B2) stimulated the DNA synthesis of hepatocytes (especially PGD2 and PGE1), 2) ethanol decreased DNA synthesis by clear dose-dependent manner, 3) the combined treatment of PGD2 or PGE1, prevents the decreasing of DNA synthesis, which was induced by ethanol, 4) in ethanol treatment, lipid peroxidation was decreased significantly, but PGD2, PGE1 and PGA1 were not affected, and 5) PGD2, PGE1 and PGA1 decreased lipid peroxidation with ethanol, significantly. CONCLUSIONS: From these results, we concluded that PG could be useful for the treatment of degenerative liver disease and alcohol-induced liver disease in the assumption that further studies on the action mechanisms of PG will continue.
Animal
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Cells, Cultured
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DNA/biosynthesis
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Drug Interactions
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Ethanol/toxicity*
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Lipid Peroxidation/drug effects
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Liver/metabolism
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Liver/drug effects*
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Prostaglandins, Synthetic/pharmacology*
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Rats
8.Prostaglandin induces the expression of matrix metalloproteinase-1 in ciliary melanocytes.
Ning-li WANG ; Qing-jun LU ; Jun-hong LI ; Ling WANG
Chinese Medical Journal 2008;121(13):1173-1176
BACKGROUNDLatanoprost, a prostaglandin F2alpha analog, has been shown to be an effective intraocular pressure lowering agent which acts by inducing ciliary muscle cells to synthesise matrix metalloproteinases. However, the response of ciliary melanocytes to latanoprost has never been reported. This research has investigated the ability of latanoprost to induce matrix metalloproteinase-1 expression in human ciliary melanocytes, and thereby advance the understanding of the mechanism of PGF(2alpha) in decreasing intraocular pressure.
METHODSIn vitro human ciliary melanocytes were treated for 48 hours with five different concentrations of latanoprost (100, 150, 200, 500, and 1000 nmol/L). Ciliary melanocytes treated with 0.01% ethanol (vehicle) were used as a control. The expression of matrix metalloproteinase-1 in ciliary melanocytes was determined by Western blotting and immunofluorescent staining.
RESULTSWestern blotting showed that the expression of matrix metalloproteinase-1 in ciliary melanocytes was induced by latanoprost, and the level of expression was dependent on the concentration of latanoprost in the culture medium. Immunofluorescent staining showed that matrix metalloproteinase-1 was confined to the ciliary melanocyte cytoplasm.
CONCLUSIONSLatanoprost induced the expression of matrix metalloproteinase-1 in human ciliary melanocytes in a dose-dependent manner. Ciliary melanocytes, as well as ciliary muscle cells, may also play an important role in uveoscleral outflow modulation.
Cells, Cultured ; Ciliary Body ; cytology ; drug effects ; enzymology ; Female ; Fluorescent Antibody Technique ; Humans ; Immunoblotting ; Male ; Matrix Metalloproteinase 1 ; analysis ; Melanocytes ; drug effects ; enzymology ; Prostaglandins F, Synthetic ; pharmacology
9.Sox-4 is a positive regulator of Hep3B and HepG2 cells' apoptosis induced by prostaglandin (PG)A2 and 12-PGJ2..
Sang Gun AHN ; Ho Shik KIM ; Seong Whan JEONG ; Bo Eun KIM ; Hyang Shuk RHIM ; Jae Yong SHIM ; Jin Woo KIM ; Jeong Hwa LEE ; In Kyung KIM
Experimental & Molecular Medicine 2002;34(3):243-249
We reported earlier that expression of Sox-4 was found to be elevated during prostaglandin (PG) A2 and delta(12)-PGJ(12) induced apoptosis in human hepatocarcinoma Hep3B cells. In this study, the role of Sox-4 was examined using human Hep3B and HepG2 cell lines. Sox-4 induction by several apoptotic inducer such as A23187 (Ca(2+) ionophore) and etoposide (topoisomerase II inhibitor) and Sox-4 transfection into the cells were able to induce apoptosis as observed by the cellular DNA fragmentation. Antisense oligonucleotide of Sox-4 inhibited the induction of Sox-4 expression and blocked the formation of DNA fragmentation by PGA(2) and delta(12)-PGJ(12) in Hep3B and HepG2 cells. Sox-4-induced apoptosis was accompanied with caspase-1 activation indicating that caspase cascade was involved in this apoptotic pathway. These results indicate that Sox-4 is involved in Hep3B and HepG2 cells apoptosis as an important apoptotic mediator.
Apoptosis/*drug effects
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Blotting, Western
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Calcimycin/pharmacology
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Caspase 1/antagonists & inhibitors/metabolism
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Etoposide/pharmacology
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Gene Expression Regulation, Neoplastic/drug effects
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High Mobility Group Proteins/genetics/*metabolism
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Human
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Liver Neoplasms/enzymology/metabolism/pathology
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Oligopeptides/pharmacology
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Prostaglandin D2/*analogs & derivatives/*pharmacology
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Prostaglandins A/*pharmacology
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Trans-Activators/genetics/*metabolism
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Transfection
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Tumor Cells, Cultured
10.Prostaglandin A2 Induces Caspase-independent Apoptosis in Hepatocellular Carcinoma Cells.
Ho Shik KIM ; Jae Chun SHIM ; Ju Youn CHOI ; Hyangshuk RHIM ; In Kyung KIM
The Korean Journal of Hepatology 2005;11(1):72-79
BACKGROUND/AIMS: Prostaglandin (PG) A2 has been reported to inhibit the growth of hepatocellular carcinoma cells via activation of apoptosis, although the molecular mechanisms involved have not been clarified, yet. To investigate the mechanism of the PGA2-induced apoptosis, we analyzed the activation of caspases during the apoptosis of hepatoma cell lines. METHODS: Induction of apoptosis by PGA2 in hepatoma cell lines, Hep 3B and Hep G2, was assessed by DAPI staining of nuclei and agarose gel electrophoresis of genomic DNA. The involvement of caspases was analyzed by immunoblot analysis of poly ADP-ribose polymerase (PARP) and by checking the effect of caspase inhibitors on PGA2-induced apoptosis. RESULTS: PGA2 inhibited the growth of Hep 3B and Hep G2 cells, accompanying nuclear condensation and fragmentation, and genomic DNA laddering, which are the hallmarks of apoptosis. The PARP was not cleaved during the apoptosis of Hep 3B and Hep G2 cells and caspase inhibitors such as z-VAD-Fmk and z-DEVD-Fmk exerted no effect on the PGA2-induced apoptosis. CONCLUSIONS: These results suggest that PGA2 induces apoptosis in Hep 3B and Hep G2 cells via caspase-independent pathway.
Apoptosis/*drug effects
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Carcinoma, Hepatocellular/*pathology
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Caspases/antagonists & inhibitors/*metabolism
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Cell Line, Tumor
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Cell Proliferation/drug effects
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Enzyme Activation
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Humans
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Liver Neoplasms/*pathology
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Prostaglandins A/*pharmacology
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Research Support, Non-U.S. Gov't
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Tumor Cells, Cultured