Role of prostaglandins generated by cyclooxygenase-1 and cyclooxygenase-2 in healing of ischemia–reperfusion-induced gastric lesions

Brzozowski, Tomasz; Konturek, Peter C.; Konturek, Stanisław J.; Śliwowski, Zbigniew; Drozdowicz, Danuta; Stachura, Jerzy; Pajdo, Robert; Hahn, Eckhart G.

doi:10.1016/s0014-2999(99)00681-0

Cited by 89 publications

(67 citation statements)

References 36 publications

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“…Thereafter, natural recovery reduced it gradually, and on the 7th day, the DS value was less than that of the day of ulcer induction. We have chosen the dose of trans-resveratrol (10 mg/kg), based on a previous report (Brzozowski et al, 1999), which was also supported by our dose-dependent study (Fig. 3B).…”

Section: Resultsmentioning

confidence: 58%

“…The chemopreventive activity of trans-resveratrol has been demonstrated notably in breast cancer (Scarlatti et al, 2003) and leukemia (Gao et al, 2002). It has also been found that successive treatment of trans-resveratrol delays ulcer healing induced by ischemia reperfusion and acetic acid (Brzozowski et al, 1999(Brzozowski et al, , 2001). This kind of ulcerogenic properties of trans-resveratrol demands for the design of its new potential analogs, especially for chemotherapeutic purpose but certainly has to be devoid of ulcerogenic properties, which is a major disadvantage of trans-resveratrol.…”

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confidence: 99%

“…Earlier, trans-resveratrol treatment was found to delay healing of gastric ulcer induced by ischemia-reperfusion and acetic acid (Brzozowski et al, 1999(Brzozowski et al, , 2001) by reducing PGE 2 synthesis via specific inhibition of cyclooxygenase (COX)-1. Later, trans-resveratrol was also found to suppress the phorbol ester-induced COX-2 mRNA expression (Subbaramaiah et al, 1998).…”

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confidence: 99%

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Improved Antiulcer and Anticancer Properties of a trans-Resveratrol Analog in Mice

Guha¹,

Dey²,

Sarkar³

et al. 2008

J Pharmacol Exp Ther

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Despite its potential, use of trans-resveratrol as an anticancer drug is severely constrained because of its tendency to prolong gastric ulceration. We found that in addition to delaying ulcer healing, trans-resveratrol also aggravated acute gastric ulceration induced by the nonsteroidal anti-inflammatory drugs by reducing the synthesis of prostaglandin (PG) E 2 via a specific inhibition of cyclooxygenase (COX)-1 that also hampered angiogenesis. However, for the first time, we showed that the 3Ј-5Ј-hydroxylated congener [(E)-HST-1] of trans-resveratrol, synthesized in multigram scale, exerted potential chemotherapeutic property but was nonulcerogenic in nature, rather moderately accelerated healing of indomethacin-induced gastric ulceration. HST-1 did not suppress COX-1, COX-2 expression, and PGE 2 synthesis but reduced the level of inflammatory myeloperoxidase (MPO) activity. The healing was augmented primarily through the nitric oxide synthase (NOS)-dependent pathway. HST-1 treatment induced endothelial NOS (eNOS) expression and reduced inducible NOS (iNOS), resulting in increased eNOS/iNOS ratio. The selective iNOS inhibitor [L-N 6 -(1-iminoethyl) lysine hydrochloride] and nonselective NOS inhibitor (N -nitro-L-arginine methyl ester) treatment revealed that eNOS could be the probable molecular switch to accelerate the indomethacin-induced ulcer healing in HST-1-treated mice. Furthermore, the anticancer effect of HST-1 on U937 and K562 leukemia cell lines was found to be significantly better than that of trans-resveratrol. Overall, these established HST-1 as a potentially better anticancer compound than trans-resveratrol, considering it is devoid of any ulcerogenic side effects. In conclusion, for the first time, we showed that a novel analog of trans-resveratrol, HST-1, was devoid of ulcerogenic adversative effects of trans-resveratrol but retained potentially better anticancer property.

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Section: Resultsmentioning

confidence: 58%

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confidence: 99%

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confidence: 99%

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Improved Antiulcer and Anticancer Properties of a trans-Resveratrol Analog in Mice

Guha¹,

Dey²,

Sarkar³

et al. 2008

J Pharmacol Exp Ther

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“…Constitutively active Cox-I was selectively inhibited with 1 pM or 10 pM resveratrol (Cayman Chemical, Ann Arbor, MI) [14,31,36]. Resveratrol can also inhibit the inducible form of the enzyme by suppressing Cox-2 mRNA production [59], although this requires higher levels of resveratrol.…”

Section: Role Of' Prostaglandin In the Pemf Responsementioning

confidence: 99%

Pulsed electromagnetic fields affect phenotype and connexin 43 protein expression in MLO‐Y4 osteocyte‐like cells and ROS 17/2.8 osteoblast‐like cells

Lohmann

Schwartz

Liu

et al. 2003

Journal Orthopaedic Research

120

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Osteocytes, the predominant cells in bone, are postulated to be responsible for sensing mechanical and electrical stimuli, transducing signals via gap junctions. Osteocytes respond to induced shear by increasing connexin 43 (Cx43) levels, suggesting that they might be sensitive to physical stimuli like low-frequency electromagnetic fields (EMF). Immature osteoblasts exhibit decreased intercellular communication in response to EMF but no change in Cx43. Here, we examined long term effects of pulsed EMF (PEMF) on MLO-Y4 osteocyte-like cells and ROS 17/23 osteoblast-like cells. In MLO-Y4 cell cultures, PEMF for 8 h/day for one, two or four days increased alkaline phosphatase activity but had no effect on cell number or osteocalcin. Transforming growth factor beta-1 (TGF-PI) and prostaglandin EZ were increased, and NO2-was altered. PEMFs effect on TGF-Pl was via a prostaglandin-dependent mechanism involving Cox-1 but not Cox-2. In ROS 17/2.X cells, PEMF for 24, 4X or 72 h did not affect cell number, osteocalcin mRNA or osteocalcin protein. PEMF reduced Cx43 protein in both cells. Longer exposures decreased Cx43 mRNA. This indicates that cells in the osteoblast lineage, including well-differentiated osteoblast-like ROS 17/23 cells and terminally differentiated osteocyte-like MLO-Y4 cells, respond to PEMF with changes in local factor production and reduced Cx43, suggesting decreased gap junctional signaling.

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“…The present study showed that the area and depth of gastric mucosal lesions caused by hemorrhagic shock-reperfusion in the gastric corpus of rats were more severe than those in the antrum. This indicated that there were differences in resistance in gastric mucosa of the corpus and the antrum, which was probably related to differences in gastric mucosal blood flow, energy metabolism and the capacity to dispose the influxing hydrogen ion, but most propably was related with the different distribution of endogenous PGs and the different ability of anti-oxidation [29][30][31][32][33] . The present study also showed that the protective role of EFRRS was different in the gastric corpus and the antrum, EFRRS possessed more powerful capability to reduce the area of lesions and to lighten the extent of lesions in corpus than those in the antrum, indicating EFRRS had potential protective effect on the corpus mucosa, which was related to the higher changes of PGs and OFR in the corpus caused by EFRRS.…”

Section: Discussionmentioning

confidence: 99%

Effects of extract F of red-rooted Salvia on mucosal lesions of gastric corpus and antrum induced by hemorrhagic shock-reperfusion in rats

Zhang¹,

Yao²,

Li³

2001

WJG

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AIM To compare the effects of extract F of red-rooted Salvia (EFRRS) on mucosal lesions of gastric corpus and antrum induced by hemorrhagic shock and reperfusion in rats.METHODS The rats were subject to hemorrhagic shock and followed by reperfusion, and were divided randomly into two groups. Group 1 received saline, and group 2 received EFRRS intravenously. The index of gastric mucosal lesions (IGML) was expressed as the percentage of lesional area in the corpus or antrum. The degree of gastric mucosal lesions (DGML) was catalogued grade 0, 1, 2 and 3. The concentrations of prostaglandins (PGs) were measured by radioimmunoassay. The concentration of MDA was measured according to the procedures of Asakawa. The activity of SOD was measured by the biochemical way. The growth rates or inhibitory rates of above-mentioned parametes were calculated.RESULTS As compared with IGML (%), grade 3 damage (%) and MDA content (nmol/g tissue) of gastric antrum which were respectively 7.96±0.59 , 34.86±4.96 and 156.98±16.12, those of gastric corpus which were respectively 23.18±6.82, 58.44±9.07 and 230.56±19.37 increased markedly (P<0.01), whereas the grade 0 damage, grade 1 damage, the concentrat ions of PGE 2 and PGI 2 (pg/mg tissue), the ratio of PGI 2 /TXA 2 and the activity of SOD (U/g tissue) of corpus which were respectively 3.01±1. 01, 8.35±1.95, 540.48±182.78, 714.38±123.74, 17.38±5.93 and 134.29±13.35 were markedly lower than those of antrum which were respectively 13.92±2.25, 26.78±6.06, 2218.56±433.12, 2531.76±492.35, 43.46±8.51 and 187.45±17.67 (P<0.01) after hemorrhagic shock and reperfusion. After intravenous EFRRS, the growth rates (%) of grade 0 damage, grade 1 damage, the concentrations of PGE2 and PGI 2 , the ratio of PGI 2 /TXA 2 and the activity of SOD of corpus which were respectively 632.56, 308.62, 40.75, 74.75, 92.29 and 122.25 were higher than those in antrum which were respectively 104. 89, 58.40, 11.12, 56.58, 30.65 and 82.64, whereas the inhibitory rates (%) of IGML, grade 3 damage and MDA content of gastric corpus were 82.93, 65.32 and 59.09, being higher than those of gastric antrum which were 76.64, 53.18 and 42.37.CONCLUSION After hemorrhagic shock-reperfusion, the gastric mucosal lesions in the corpus were more severe than those in the antrum, which were related not only to the different distribution of endogenous PGs in the mucosa, but also to the different ability of antioxidation of the mucosa. The protective effect of EFRRS on the gastric mucosa in the corpus was more evident than that in the antrum, which was related to higher growth degree of PGs contents and antioxitative ability in gastric corpus after administratio n of EFRRS.Subject headings plant extracts/pharmacology; gastric mucosa/pathology; shock hemorrhagic; reperfusion; hydroxyl radical Zhang LH, Yao CB, Li HQ. Effects of extract F of red-rooted Salvia on mucosal lesions of gastric corpus and antrum induced by hemorrhagic shock-reperfusion in rats. World J Gastroenterol, 2001; 7(4):672-677

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Role of prostaglandins generated by cyclooxygenase-1 and cyclooxygenase-2 in healing of ischemia–reperfusion-induced gastric lesions

Cited by 89 publications

References 36 publications

Improved Antiulcer and Anticancer Properties of a trans-Resveratrol Analog in Mice

Improved Antiulcer and Anticancer Properties of a trans-Resveratrol Analog in Mice

Pulsed electromagnetic fields affect phenotype and connexin 43 protein expression in MLO‐Y4 osteocyte‐like cells and ROS 17/2.8 osteoblast‐like cells

Effects of extract F of red-rooted Salvia on mucosal lesions of gastric corpus and antrum induced by hemorrhagic shock-reperfusion in rats

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