Protection by Opioids against Gastric Lesions Caused by Necrotizing Agents

Ferri, Sergio Solbes; Speroni, Ester; Candeletti, Sanzio; Cavicchini, E.; Romualdi, Patrizia; Govoni, Paolo; Marchini, M

doi:10.1159/000138371

Cited by 20 publications

(6 citation statements)

References 12 publications

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“…11 Studies have shown that opioid receptor activation by exogenous agonists can facilitate a protective effect against hypoxia, ischemia, cold, or an acidic environment. [12][13][14] More recently, we published that morphine pretreatment can provide significant retinal neuroprotection against acute ischemic 15 and glaucomatous injury, 16 and this neuroprotection is mediated, in part, via inhibition of TNF-a production. 16,17 However, the neuroprotective roles of d-opioid receptors against glaucomatous injury have remained fully unexplored.…”

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confidence: 99%

Delta-Opioid Agonist SNC-121 Protects Retinal Ganglion Cell Function in a Chronic Ocular Hypertensive Rat Model

Abdul

Akhter²,

Husain³

2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. This study examined if the delta-opioid (d-opioid) receptor agonist, SNC-121, can improve retinal function and retinal ganglion cell (RGC) survival during glaucomatous injury in a chronic ocular hypertensive rat model. METHODS.IOP was raised in brown Norway rats by injecting hypertonic saline into the limbal venous system. Rats were treated with 1 mg/kg SNC-121 (intraperitoneally [IP]) once daily for 7 days. Pattern-electroretinograms (PERGs) were obtained in response to contrast reversal of patterned visual stimuli. RGCs were visualized by fluorogold retrograde labeling. Expression of TNF-a and p38 mitogen-activated protein (MAP) kinase was measured by immunohistochemistry and Western blotting.RESULTS. PERG amplitudes in ocular hypertensive eyes were significantly reduced (14.3 6 0.60 lvolts) when compared with healthy eyes (18.0 6 0.62 lvolts). PERG loss in hypertensive eyes was inhibited by SNC-121 treatment (17.20 6 0.1.3 lvolts; P < 0.05). There was a 29% loss of RGCs in the ocular hypertensive eye, which was inhibited in the presence of SNC-121. TNF-a production and activation of p38 MAP kinase in retinal sections and optic nerve samples were upregulated in ocular hypertensive eyes and inhibited in the presence of SNC-121. Furthermore, TNF-a induced increase in p38 MAP kinase activation in astrocytes was inhibited in the presence of SNC-121.CONCLUSIONS. These data provide evidence that activation of dopioid receptors inhibited the loss of PERG amplitudes and rate of RGC loss during glaucomatous injury. Mechanistic data provided clues that TNF-a is mainly produced from glial cells and activates p38 MAP kinase, which was significantly inhibited by SNC-121 treatment. Overall, data indicate that enhancement of d-opioidergic activity in the eye may provide retina neuroprotection against glaucoma. (Invest Ophthalmol Vis Sci.

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confidence: 99%

Delta-Opioid Agonist SNC-121 Protects Retinal Ganglion Cell Function in a Chronic Ocular Hypertensive Rat Model

Abdul

Akhter²,

Husain³

2013

Invest. Ophthalmol. Vis. Sci.

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“…9 In other systems, opioid-receptor activation by exogenous agonists (like endogenous opioid-induced preconditioning) has been shown to facilitate a protective effect against hypoxia, ischemia, cold, or an acidic environment. [10][11][12] Recently, we published novel findings that morphine pretreatment can provide significant retinal neuroprotection against acute ischemic injury, 8 and this neuroprotection is mediated in part, via inhibition of TNF-a production. 13 TNF-a is a proinflammatory cytokine that is rapidly upregulated in several neurodegenerative disorders, such as multiple sclerosis, Parkinson disease, Alzheimer disease, and glaucoma.…”

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confidence: 99%

Preservation of Retina Ganglion Cell Function by Morphine in a Chronic Ocular-Hypertensive Rat Model

Husain

Abdul²,

Crosson³

2012

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The current study examined if opioid-receptoractivation by morphine can improve retinal function and retinal ganglion cell (RGC) integrity in a chronic glaucoma rat model. METHODS.IOP was raised in Brown Norway rats by injecting hypertonic saline into the limbal venous system. Rats were treated daily with 1 mg/kg morphine for 28 days at 24-hour intervals; animals were examined for changes in IOP by a TonoLab tonometer. Pattern-ERG (PERG) was obtained in response to contrast-reversal of patterned visual stimuli. RGCs were visualized by fluorogold retrograde-labeling. Changes in the expression pattern of TNF-a and caspases were measured by Western blotting.RESULTS. A significant IOP elevation was seen as early as 7 days, and maintained for up to 8 weeks, after surgery. PERG amplitudes were significantly reduced in ocular-hypertensive eyes (15.84 6 0.74 lvolts) when compared with normal eyes (19 6 0.86 lvolts). PERG deficits in hypertensive eyes were reversed by morphine treatment (18.23 6 0.78 lvolts; P < 0.05). In untreated rats, a 24% reduction in labeled RGCs was measured in the hypertensive eye compared with the normal eye. This reduction in RGC labeling was significantly ameliorated in the presence of morphine. In retinal samples, TNF-a, caspase-8, and caspase-3 expressions were significantly upregulated in ocular hypertensive eyes, but completely inhibited in the morphine-treated animals.CONCLUSIONS. These data provide evidence that activation of opioid receptors can provide significant improvement in PERG and RGC integrity against glaucomatous injury. Mechanistic data provide clues that activation of one or more opioid receptors can reduce glaucomatous-injury via suppression of TNF-a and caspase activation. (Invest Ophthalmol Vis Sci.

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“…or intraperitoneal (i.p.) administra tions of morphine and a synthetic met-enkephalin analogue (FK33-824) were effica cious in preventing experimental ulcers in the rat [5,6], The findings seemed to be related to an involvement of opioid receptors because the blockade of these receptors, with naloxone [4,7] or naltrexone [8], prevented the gastric protection induced by morphine or FK33-824 [4]. It has also been described that both cen tral and peripheral p-and 5-opioid receptors were the functionally important species that could mediate these effects [9.…”

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confidence: 97%

Central and Peripheral Involvement of Endogenous Opioid Peptides in Gastric Protection in Stressed Rats

Scoto

Parenti²

1996

Pharmacology

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The effects of intraperitoneal and intracerebroventricular administration of the inhibitor of endopeptidase EC 24.11 (enkephalinase), thiorphan, and the synthetic enkephalin analogue [D-Ala²-Met⁵]enkephalinamide (DALA) were investigated in cold-restraint-stressed rats. Drugs were administered alone or after pretreatment with naloxone or naloxone methiodide given 20 min prior to the drugs. Thiorphan and DALA, administered centrally (4 µg i.c.v./rat) or peripherally (400 µg/kg), induced a significant gastric protection. Prior treatment with naloxone s.c. (1 mg/kg) inhibited the effect induced by i.e.v. or i.p. injections of thiorphan or DALA. In contrast, s.c. administration of naloxone methiodide (1 mg/ kg) did not affect the response induced by central administration of thiorphan or DALA, but was able to prevent that of thiorphan or DALA when they were administered i.p. These data strongly support the hypothesis of a central and peripheral involvement of endogenous opioid peptides in gastric protection in stressed rats.

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Protection by Opioids against Gastric Lesions Caused by Necrotizing Agents

Cited by 20 publications

References 12 publications

Delta-Opioid Agonist SNC-121 Protects Retinal Ganglion Cell Function in a Chronic Ocular Hypertensive Rat Model

Delta-Opioid Agonist SNC-121 Protects Retinal Ganglion Cell Function in a Chronic Ocular Hypertensive Rat Model

Preservation of Retina Ganglion Cell Function by Morphine in a Chronic Ocular-Hypertensive Rat Model

Central and Peripheral Involvement of Endogenous Opioid Peptides in Gastric Protection in Stressed Rats

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