Nitric oxide enhances prostaglandin production in ethanol-induced gastric mucosal injury in rats

Franco, L.; Doria, Denise

doi:10.1016/s0014-2999(98)00161-7

Cited by 25 publications

(22 citation statements)

References 26 publications

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“…In agreement with other data [11][12][13], pretreatment of rats with different doses of bacterial LPS 5 h prior to ethanol treatment reduced the extent of mucosal hemorrhagic damage in response to intraluminal ethanol. It is well known that iNOS is responsible for the increase in the synthesis of NO that occurs some 3-6 h after exposure to endotoxin [16].…”

Section: Discussionsupporting

confidence: 92%

“…Treatment of rats with graded doses of LPS, injected 5 h before ethanol, resulted in a reduction of the damage associated with 95% ethanol administration. The time interval between LPS administration and ethanol application was selected from previous studies in which we showed that 5 h was the optimal time required for the induction of prostaglandins and iNOS in the rat stomach [13]. The ex vivo production of nitrite and PGE 2 in the rats' gastric mucosa incubated for 5 h was increased in a dose-dependent manner in LPStreated rats (fig.…”

Section: Resultsmentioning

confidence: 99%

“…The iNOS can produce consistent, high concentrations of NO that have been shown to contribute to gastric damage, particularly when cells are exposed to large quantities of NO over an extended period of time [9,10]. In contrast to these studies, it has been suggested that NO derived from iNOS plays an important role in maintaining mucosal integrity in some circumstances [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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Role of Nitric Oxide and Prostaglandin E<sub>2</sub> in Gastroprotection Induced by Lipopolysaccharide in Ethanol-Mediated Damage in Rats

Franco¹,

Doria²

2001

Med Princ Pract

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Objective: This study was designed to investigate the role of endogenous nitric oxide (NO) and prostaglandin E₂ (PGE₂) in the gastroprotection induced by lipopolysaccharide (LPS). Methods: Ethanol was used to induce gastric lesions in control rats and in rats pretreated with graded doses of LPS administered at different time intervals and with inhibitors of NO synthase or prostaglandin synthesis. The ethanol-induced damage on gastric mucosa was assessed by measuring the extent of the lesion. We evaluated nitrite, a breakdown of NO, and PGE₂ accumulation in ex vivo gastric mucosa. Results: The ex vivo production of both NO and PGE₂ was increased in a dose-dependent manner by LPS injected 5 h before ethanol. Pretreatment with L-N⁶-(1-iminoethyl)lysine(dihydrochloride) inhibited the protection associated with LPS and the ex vivo increase of both NO and PGE₂. Indomethacin was ineffective in suppressing LPS-mediated protection against ethanol-induced damage and in suppressing ex vivo increase of nitrite whereas the ex vivo increase of PGE₂ was prevented in a dose-dependent manner. When ethanol was administered 30 min after LPS, there was a lack of protection and a lack of increase of NO and PGE₂. Conclusion: These results indicate that the reduction in ethanol-mediated damage in LPS-treated rats depends on endogenous PGE₂ formation and on endogenous NO produced by stimulation of inducible NO synthase.

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Section: Discussionsupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Role of Nitric Oxide and Prostaglandin E<sub>2</sub> in Gastroprotection Induced by Lipopolysaccharide in Ethanol-Mediated Damage in Rats

Franco¹,

Doria²

2001

Med Princ Pract

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“…Exposure of the gastrointestinal tract to ethanol has been used in a variety of animal species to produce inflammation and ulceration of the stomach, duodenum, ileum, or colon (5,12,14,37,43). When neutrophil infiltration into the colon was examined at various times after intracolonic instillation of 30% ethanol, MPO activity was maximal at 24 h and returned to baseline at 2 wk.…”

Section: Discussionmentioning

confidence: 99%

Quantitative assessment and characterization of visceral nociception and hyperalgesia in mice

Kamp

Jones

Tillman

et al. 2003

American Journal of Physiology-Gastrointestinal and Liver Physi

102

108

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Colorectal distension (CRD) is a well-characterized model of visceral nociception, which we adapted to the mouse. CRD reproducibly evoked contractions of the abdominal musculature [visceromotor response (VMR)], which was graded to stimulus intensity. The magnitude of VMR was greater in male C57BL6 and female 129S6 mice than in male 129S6 and B6.129 mice. In 129S6, C57BL6, and B6.129 mice strains, VMR was reduced dose dependently by morphine (1-10 mg/kg) and by the -opioid agonist U-69593 (0.2-2 mg/kg), although U-69593 was significantly less potent in C57BL6 mice. In additional experiments, the VMR was recorded from adult male 129S6 mice before and after intracolonic administration of various irritants. Only 30% ethanol significantly enhanced responses to CRD. The colon hyperalgesia persisted for 14 days and was associated with a significant shift of the morphine doseresponse function to the left. We believe this will be a useful model for study of visceral nociception and hyperalgesia, including studies of transgenic mice with mutations relevant to pain. colon; visceral pain; knockout mice; strain; gender; -opioid PAIN IS THE MOST COMMON REASON patients seek care from a physician, and the majority of visits are for pain of visceral origin. Current knowledge about mechanisms of pain has been derived from studies of somatic, principally cutaneous pain. Visceral pain has been less well studied, in part, because of more difficult access to visceral structures. Additionally, stimuli that are painful when applied to the skin, such as burning, crushing, and cutting, evoke no pain when applied to most visceral structures. Furthermore, there is growing evidence that the mechanisms of visceral and cutaneous pain are different (8,19). Certainly, the characteristics of these pains are different; visceral pain is diffuse, poorly localized, and referred to overlying structures (see Refs. 7 and 46 for reviews).Balloon distension of hollow organs, such as the colon, stomach, or urinary bladder produces pain in humans and quantifiable behavioral and autonomic responses in nonhuman animals. These responses have been most extensively characterized for colorectal distension (CRD) in the rat. When applied to rats at pressures comparable to those that produce pain in humans, CRD is aversive and produces tachycardia, pressor effects, contraction of the abdominal musculature, activation of afferent (sensory) fibers in the pelvic nerve, and activation of second-order neurons in the dorsal horn of the spinal cord (45,46,52).The availability of genetically modified mice has increased interest in the mouse as a nonhuman experimental animal. Numerous mice have been generated with mutations relevant to the study of pain; most have been tested in cutaneous models of nociception only. Some transgenic mice have been tested using the intraperitoneal acetic acid model of visceral nociception (writhing test); however, a limited understanding of the underlying structures and sensory neurons activated in this model confounds interpretation of resul...

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“…30) Gastric acidity although does not have a prominent role in ethanol-induced mucosal injury, the present finding that CPA reduces gastric acidity has relevance for its protection against indomethacin. 17) Since the protection afforded by CPA is additionally indomethacinand L-NAME-sensitive, it is suggested that under these conditions endogenous prostaglandins and nitric oxide act as activators of K ϩ ATP channels, 29,31) and this mechanism, at least in part, mediates gastroprotection. The more effective blockade of CPA gastroprotection by K ϩ ATP channel blocker glibenclamide confirms this view.…”

Section: Discussionmentioning

confidence: 99%

Gastroprotective Mechanisms of Centipedic Acid, a Natural Diterpene from Egletes viscosa LESS.

Guedes

Carvalho

Lima

et al. 2008

Biological & Pharmaceutical Bulletin

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Peptic ulcer disease and gastric dispepsia-associated with chronic use of therapeuticals such as nonsteroidal anti-inflammatory drugs (NSAIDs) and anticancer agents are the two major causes that adversely affect the life quality. Presently used antisecretory agents like proton pump inhibitors may represent a key option in peptic ulcer therapy 1) but their prolonged use seems to be associated with high incidence of hip fractures.2) Non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastropathy remains a major clinical problem, 3) which has not been solved through the introduction of selective inhibitors of cyclooxygenase-2 (COX-2) due to cardiac side effects.4) Similar to NSAIDs, many cancer chemotherapeuticals such as cisplatin, and bisphosphonates like alendronate can induce gastric dyspepsia. 5,6) In recent years, there is an active search to discover novel and alternative agents useful to combat gastric dyspepsia, and peptic ulcer disease.Diterpenoids form a large class of secondary metabolites isolated from plants that possess a wide spectrum of pharmacological profile that include anti-inflammatory, antimicrobial, antispasmodic, cytotoxic, antitumor and gastroprotective properties. 7,8) Of particular interest of gastroprotective diterpenes are the clerodanes (trans-dehydrocrotonin from Croton cajucara, and aparisthman from Aparisthmium cordatum), the labdanes (solidagenone from Solidago chilensis and 15-acetoxylabd-8(17)-en-19-ol as well as 15,19-diacetoxylabd-8(17)-en from Araucaria araucana), abietane (ferruginol from Prumnopitys andin), and Jatrophone from Jatropha isabelli, 9,10) which may play a major role in drug discovery as well, in providing lead structures for the development of synthetic molecules. 11,12) In several parts of Brazil, tea or decoction prepared from the flower buds of Egletes viscosa (Asteraceae) is a popular remedy for the treatment of digestive and intestinal problems.13) Phytochemical studies on flower buds revealed the presence of diterpene compounds, centipedic acid (CPA) and 12-acetoxy-hawtriwaic acid lactone (tanabalin), and a tetramethoxy flavone, ternatin.14) Pharmacological investigations identified the anti-inflammatory, hepatoprotective, antidiarrhoeal and gastroprotective properties of ternatin. 15,16) In a previous study, we established the gastroprotective effects of both CPA and tanabolin against indomethacin and ethanolinduced gastric lesions, validating the traditional use of E. viscosa.17) However, the gastroprotective mechanisms were not elucidated. Experimental and clinical evidence suggests that oxidative stress and increased acid secretion play a pivotal role in the etiopathology of gastric ulcer disease and antioxidants and antacid agents can afford gastric cytoprotection.18) The present study was mainly aimed to probe into the gastroprotective mechanisms of CPA, using the mouse model of gastric damage induced by 96% ethanol to study the role of oxidative stress and capsaicin-sensitive sensory afferents and the 4-h pylorus-ligated rat to verify whether or...

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Nitric oxide enhances prostaglandin production in ethanol-induced gastric mucosal injury in rats

Cited by 25 publications

References 26 publications

Role of Nitric Oxide and Prostaglandin E<sub>2</sub> in Gastroprotection Induced by Lipopolysaccharide in Ethanol-Mediated Damage in Rats

Role of Nitric Oxide and Prostaglandin E<sub>2</sub> in Gastroprotection Induced by Lipopolysaccharide in Ethanol-Mediated Damage in Rats

Quantitative assessment and characterization of visceral nociception and hyperalgesia in mice

Gastroprotective Mechanisms of Centipedic Acid, a Natural Diterpene from Egletes viscosa LESS.

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