The COX inhibitors indomethacin and meloxicam exhibit anti-emetic activity against cisplatin-induced emesis in piglets

Girod, Vincent; Dapzol, Julien; Bouvier, Michel; Grélot, Laurent

doi:10.1016/s0028-3908(01)00182-4

Cited by 34 publications

(14 citation statements)

References 37 publications

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“…We have attributed the emetogenicity of 2-AG to its rapid metabolism since its major metabolite (arachidonic acid) is also a potent vomit inducer, and the emetic capacity of both emetogens can be prevented in the least shrew by the cyclooxygenase inhibitor, indomethacin. Not surprisingly, indomethacin has also been shown to attenuate cisplatin-induced emesis in piglets [126]. Furthermore, pretreatment with either anandamide, methanandamide, phyto-, or synthetic cannabinoids prevents the ability of 2-AG to cause emesis in the least shrew [11].…”

Section: The Nature Of Pro- and Antiemetic Actions Of Endocannabinmentioning

confidence: 99%

Mechanisms of Broad-Spectrum Antiemetic Efficacy of Cannabinoids against Chemotherapy-Induced Acute and Delayed Vomiting

Darmani

2010

Pharmaceuticals

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Chemotherapy-induced nausea and vomiting (CINV) is a complex pathophysiological condition and consists of two phases. The conventional CINV neurotransmitter hypothesis suggests that the immediate phase is mainly due to release of serotonin (5-HT) from the enterochromaffin cells in the gastrointestinal tract (GIT), while the delayed phase is a consequence of release of substance P (SP) in the brainstem. However, more recent findings argue against this simplistic neurotransmitter and anatomical view of CINV. Revision of the hypothesis advocates a more complex, differential and overlapping involvement of several emetic neurotransmitters/modulators (e.g. dopamine, serotonin, substance P, prostaglandins and related arachidonic acid derived metabolites) in both phases of emesis occurring concomitantly in the brainstem and in the GIT enteric nervous system (ENS) [1]. No single antiemetic is currently available to completely prevent both phases of CINV. The standard antiemetic regimens include a 5-HT3 antagonist plus dexamethasone for the prevention of acute emetic phase, combined with an NK1 receptor antagonist (e.g. aprepitant) for the delayed phase. Although NK1 antagonists behave in animals as broad-spectrum antiemetics against different emetogens including cisplatin-induced acute and delayed vomiting, by themselves they are not very effective against CINV in cancer patients. Cannabinoids such as Δ9-THC also behave as broad-spectrum antiemetics against diverse emetic stimuli as well as being effective against both phases of CINV in animals and patients. Potential side effects may limit the clinical utility of direct-acting cannabinoid agonists which could be avoided by the use of corresponding indirect-acting agonists. Cannabinoids (both phyto-derived and synthetic) behave as agonist antiemetics via the activation of cannabinoid CB1 receptors in both the brainstem and the ENS emetic loci. An endocannabinoid antiemetic tone may exist since inverse CB1 agonists (but not the corresponding silent antagonists) cause nausea and vomiting.

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Section: The Nature Of Pro- and Antiemetic Actions Of Endocannabinmentioning

confidence: 99%

Mechanisms of Broad-Spectrum Antiemetic Efficacy of Cannabinoids against Chemotherapy-Induced Acute and Delayed Vomiting

Darmani

2010

Pharmaceuticals

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“…Piglets consistently respond to cisplatin by acute and delayed emesis [67]. This response is sensitive to 5-HT3 receptor antagonists and to COX inhibitors [68]. LPS administered intraperitoneally also induces vomiting in piglets.…”

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confidence: 99%

“…LPS administered intraperitoneally also induces vomiting in piglets. This response is accompanied by increased circulating levels of TNF-· [69] and blocked by bilateral vagotomy and by COX inhibitors [68].There is evidence that IL-6 plays a significant role in the development of cancer cachexia. As mentioned above, IL-6 has little effect of its own on food intake.…”

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confidence: 99%

A Cytokine-Based Neuroimmunologic Mechanism of Cancer-Related Symptoms

Lee¹,

Dantzer

Langley

et al. 2004

Neuroimmunomodulation

266

184

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While many of the multiple symptoms that cancer patients have are due to the disease, it is increasingly recognized that pain, fatigue, sleep disturbance, cognitive dysfunction and affective symptoms are treatment related, and may lead to treatment delays or premature treatment termination. This symptom burden, a subjective counterpart of tumor burden, causes significant distress. Progress in understanding the mechanisms that underlie these symptoms may lead to new therapies for symptom control. Recently, some of these symptoms have been related to the actions of certain cytokines that produce a constellation of symptoms and behavioral signs when given exogenously to both humans and animals. The cytokine-induced sickness behavior that occurs in animals after the administration of infectious or inflammatory agents or certain proinflammatory cytokines has much in common with the symptoms experienced by cancer patients. Accordingly, we propose that cancer-related symptom clusters share common cytokine-based neuroimmunologic mechanisms. In this review, we provide evidence from clinical and animal studies that correlate the altered cytokine profile with cancer-related symptoms. We also propose that the expression of coexisting symptoms is linked to the deregulated activity of nuclear factor-kappa B, the transcription factor responsible for the production of cytokines and mediators of the inflammatory responses due to cancer and/or cancer treatment. These concepts open exciting new avenues for translational research in the pathophysiology and treatment of cancer-related symptoms.

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“…The same single dose of meloxicam in adult pigs was used by Swindle (2007) and Friton et al (2006) in endotoxemia therapy and by Hirsch et al (2003) in mastitis-metritis-agalactia syndrome therapy. A similar dosage (0.3 mg/kg) was administered by Girod et al (2000Girod et al ( , 2002 in their studies on the antiemetic effects of meloxicam. However, Reyes et al (2002), used meloxicam in their neurological surgeries in piglets intravenously at the much higher dose of 1 mg/kg.…”

Section: Discussionmentioning

confidence: 99%

Effect of seven-day administration of carprofen or meloxicam on renal function in clinically healthy miniature pigs

Raušer¹,

Stehlík²,

Proks³

et al. 2010

Vet. Med.

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Carprofen or meloxicam are nonsteroidal anti-inflammatory drugs (NSAIDs), which may elicit a variety of renal disturbances. Prior to this study, the effects of carprofen or meloxicam on renal function in pigs were unknown. A total of 21 clinically healthy Goettingen miniature pigs (36.9 ± 7.22 kg) were divided into three groups based on what they were administered -carprofen, meloxicam or saline. First, blood was collected from the jugular vein and urine by ultrasound-guided cystocentesis. Serum urea (U) and creatinine (CR), fractional clearance of sodium (FCNa), urine gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) activities, urine protein/creatinine ratio (UP/UC), urine gamma-glutamyltransferase/creatinine ratio (GGT/CR) and urine alkaline phosphatase/creatinine ratio (ALP/CR) and urine analysis -urine specific gravity (USG) and sediment microscopy were assessed before and seven days after daily intramuscular administration (IM) of saline (1.5 ml per animal), carprofen (2 mg/kg) or meloxicam (0.1 mg/kg). All animals had identical housing, feeding and unlimited water intake and had not undergone surgery or been administered any medication for three months prior to this. All pigs served as control groups for an experimental study of fracture healing using transplantation of mesenchymal stem cells and scaffolds. The data were analyzed using a one way ANOVA and a Mann-Whitney test (P < 0.05). In pigs receiving carprofen, serum urea and creatinine were significantly decreased, compared to the control (P < 0.01) or meloxicam (P < 0.05) groups. In animals receiving meloxicam FCNa was significantly increased (P < 0.05) and urine specific gravity significantly decrease (P < 0.05) compared to the pretreatment values. Two carprofentreated pigs had a slight increase in renal tubular epithelial cells upon urine sediment examination. Intramuscular administration of carprofen or meloxicam in healthy miniature pigs for seven days causes no clinically important changes in selected renal parameters (without azotemia). However these changes indicate mild damage of renal tubules. Despite these findings, meloxicam or carprofen are recommended for analgesia in healthy pigs.

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The COX inhibitors indomethacin and meloxicam exhibit anti-emetic activity against cisplatin-induced emesis in piglets

Cited by 34 publications

References 37 publications

Mechanisms of Broad-Spectrum Antiemetic Efficacy of Cannabinoids against Chemotherapy-Induced Acute and Delayed Vomiting

Mechanisms of Broad-Spectrum Antiemetic Efficacy of Cannabinoids against Chemotherapy-Induced Acute and Delayed Vomiting

A Cytokine-Based Neuroimmunologic Mechanism of Cancer-Related Symptoms

Effect of seven-day administration of carprofen or meloxicam on renal function in clinically healthy miniature pigs

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