The opioid antagonist naltrexone blocks acute endotoxic shock by inhibiting tumor necrosis factor-α production

Greeneltch, Kristy M.; Haudenschild, Christian C.; Keegan, Achsah; Shi, Yufang

doi:10.1016/j.bbi.2003.12.001

Cited by 54 publications

(49 citation statements)

References 30 publications

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“…Indeed, opioid receptors blockade actually reduces inflammation in chemically induced colitis 13 . In fact, naltrexone, an opioid antagonist, is able to block acute endotoxic shock by inhibiting TNFα production 14 .…”

Section: Resultsmentioning

confidence: 99%

Do opioid receptors play a role in the pathogenesis of the inflammatory response in acute pancreatitis?

Penido

Coelho²,

Molan³

et al. 2012

Acta Cir. Bras.

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PURPOSE:To investigate the effect of the opioid blocker naltrexone in the inflammatory response in acute pancreatitis (AP). METHODS: Acute pancreatitis was induced in anesthetized male Wistar rats by retrograde injection of 2.5% sodium taurocholate diluted in 0.5ml saline into the main pancreatic duct. Animals were randomized to the following experimental groups: Control Group (n=9): animals received an intraperitoneal injection of saline solution (0.5ml), 15 minutes before the induction of AP. Naltrexone Group (n=9): animals received an intraperitoneal injection of naltrexone 0.5ml (15 mg/kg), 15 minutes before induction of AP. Peritoneal levels of TNF-α and serum levels of IL-6 and amylase were determined The volume of the ascitic fluid was also evaluated. Myeloperoxidase (MPO) activities were analyzed in homogenates of pulmonary tissue. RESULTS: There were no significant differences in the ascitic fluid volume, nor in TNF-a and IL-6 levels in the naltrexone group compared to controls. Treatment with naltrexone did not affect the lung MPO activity compared to control group. CONCLUSIONS: The opioid receptors don't play an important role in the pathogenesis of the inflammatory response in acute pancreatitis. If opioids affect leukocytes inflammatory signaling, there are no major implications in the pathogenesis of acute pancreatitis. Key words: Pancreatitis. Physiopathology. Receptors, Opioid. Naltrexone. Rats. RESUMO OBJETIVO:Investigar o efeito do bloqueador opióide naltrexone na resposta inflamatória da pancreatite aguda. METODOS: Pancreatite aguda foi induzida em ratos machos Wistar, através de injeção retrógada de solução de taurocolato de sódio a 2,5% nos ductos pancreáticos. Os animais foram alocados em dois grupos: Grupo controle (n=9) animais receberam 0,5 ml de solução salina intra-peritonial 15 minutos antes da indução da pancreatite aguda e Grupo naltrexone (n=9) animais receberam naltrexone (15mg/ kg de peso), em 0,5 ml de volume final por via intraperitoneal, 15 minutos antes da indução da pancreatite aguda. Foram avaliados o volume de ascite, os níveis séricos de amilase e IL-6, assim como TNF-α peritoneal e a atividade da mieloperoxidase (MPO) no tecido pulmonar. RESULTADOS: Não foram encontradas diferenças significantes nos parâmetros analisados entre o grupo que recebeu solução salina e o que recebeu naltrexone . CONCLUSÕES: Os receptores opióides não desempenham papel importante na resposta inflamatória sistêmica associada à pancreatite aguda. Se os opioides alteram a sinalização inflamatória nos leucócitos está ação não se reflete na patogênese da pancreatite aguda Descritores: Pancreatite. Fisiopatologia. Receptores Opióides. Naltrexona. Ratos. Do opioid receptors play a role in the pathogenesis of theinflammatory response in acute pancreatitis?

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Section: Resultsmentioning

confidence: 99%

Do opioid receptors play a role in the pathogenesis of the inflammatory response in acute pancreatitis?

Penido

Coelho²,

Molan³

et al. 2012

Acta Cir. Bras.

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“…Although naltrexone blocked LPS-induced TNF-α production in vivo (Fig. 1), it did not significantly inhibit LPS-induced TNF-α production in macrophages (15). There are several possible mechanisms that could account for the ability of naltrexone to inhibit systemic TNF-α production in response to LPS, including the following: i) naltrexone may induce unknown intermediates that function to directly inhibit macrophage-derived TNF-α or ii) naltrexone may induce the production of anti-inflammatory cytokines, such as IL-10, IL-4, and IL-13, which suppress LPS-induced TNF-α production (43).…”

Section: Discussionmentioning

confidence: 99%

“…However, Greeneltch et al reported that pretreatment with naltrexone (10 mg / kg, i.p.) cannot reduce liver damage in mice with acute endotoxic shock even though naltrexone prevented LPS / D-gal-induced mortality (15). The following reasons may explain the failure of hepatic protection by naltrexone in Greeneltch's endotoxic mouse study: i) The dose of naltrexone (10 mg / kg) used for mice may be too low to protect liver from severe damage because the doses of naltrexone used in rats with endotoxic shock in some reports are at 10 mg /kg (18,47) or higher (our unpublished data).…”

Section: Discussionmentioning

confidence: 99%

“…It has been claimed to have antiinflammatory and immunomodulatory effects both in vitro and in vivo (15,18,19). Our previous study indicates that pre-treatment with naltrexone has a protective effect against LPS-induced septic shock in rats (18).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, various studies have shown that TNF-α, a major mediator of septic shock, induces tissue injury, loss of blood pressure, organ failure, and ultimately death (15). Increased level of hepatotoxic cytokines such as TNF-α are well documented in alcoholic liver disease and non-alcoholic steato-hepatitis and have been shown to play a mechanistic role in both of these disease processes (16).…”

Section: Introductionmentioning

confidence: 99%

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Naltrexone Protects Against Lipopolysaccharide/D-Galactosamine–Induced Hepatitis in Mice

et al. 2008

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Abstract. Naltrexone, an opioid receptor antagonist, has been claimed to have anti-inflammatory and immunomodulatory effects both in vitro and in vivo. Thus, the aim of this study was to evaluate the effects of naltrexone on acute hepatitis induced by intraperitoneal (i.p.) administration of lipopolysaccharide (LPS, 20 μg / kg)/ D-galactosamine (D-gal, 700 mg / kg) in conscious ICR mice. Results demonstrated that post-treatment with naltrexone (20 mg / kg, i.p.) significantly attenuated the deleterious liver function in mice treated with LPS / D-gal. It was also found that naltrexone significantly inhibited the elevation of plasma tumor necrosis factor-α (TNF-α) caused by LPS/ D-gal. The overproduction of nitric oxide (NO) and superoxide anions induced by LPS / D-gal were also significantly reduced by naltrexone. Moreover, infiltration of neutrophils into the liver of mice 12 h after treatment with LPS / D-gal was also decreased by naltrexone. In conclusion, the beneficial effects of naltrexone on LPS / D-gal-induced hepatitis result from its inhibition of pro-inflammatory factors and antioxidant effects. Thus, naltrexone is of therapeutic potential for treating liver injury.

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Trauma, Shock, and Critical Care Obstetrics

Clark

Dildy

Clark

2007

Clinical Obstetrics

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The opioid antagonist naltrexone blocks acute endotoxic shock by inhibiting tumor necrosis factor-α production

Cited by 54 publications

References 30 publications

Do opioid receptors play a role in the pathogenesis of the inflammatory response in acute pancreatitis?

Do opioid receptors play a role in the pathogenesis of the inflammatory response in acute pancreatitis?

Naltrexone Protects Against Lipopolysaccharide/D-Galactosamine–Induced Hepatitis in Mice

Trauma, Shock, and Critical Care Obstetrics

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