Ketamine/Xylazine attenuates LPS-induced iNOS expression in various rat tissues

Helmer, Kenneth S.; Cui, Yan; Dewan, Ashvin K.; Mercer, David

doi:10.1016/s0022-4804(03)00138-0

Cited by 33 publications

(32 citation statements)

References 20 publications

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“…Yang et al demonstrated that ketamine, only at a supra-anesthetic dosage, could inhibit endotoxin-induced pulmonary inflammation in vivo [9]. Ketamine has been shown to attenuate symptoms of endotoxemia in a lipopolysaccharide-induced rat model of sepsis, by reducing nuclear factor kappa B (NF-kappa B) activity and tumor necrosis factor-alpha (TNF-α) production [29], and decreasing the expression of iNOS in various rat tissues [30]. Furthermore, Yu et al found that ketamine at sub-anesthetic doses also suppress the production of inflammatory cytokines on lung tissue such as TNF-α and interleukin-6 (IL-6), attenuate NF-kappa B activity, and inhibit toll-like receptor 2 (TLR2) and TLR4 expression in polymicrobial sepsis [8].…”

Section: Discussionmentioning

confidence: 99%

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The Effects of Ketamine, Midazolam and Ketamine/Xylazine on Acute Lung Injury Induced by α-Naphthylthiourea in Rats*

Erdem¹,

Yurdakan²,

Yilmaz-Sipahi³

2014

Adv Clin Exp Med

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Objectives. Ketamine is a drug used in human and veterinary medicine, primarily for the induction and maintenance of general anesthesia, analgesia (particularly in emergency medicine), and treatment of bronchospasm. Midazolam is the preferred drug in intensive care units for sedation and anesthesia. Ketamine/xylazine combination is used as an anesthetic agent in veterinary medicine and experimental animals. Aside from anaesthetic properties, these agents can cause physiologic and metabolic alterations and modulate and improve the inflammatory responses. The objective of the present study was to investigate the effects of ketamine, midazolam, and veterinary and experimentally used ketamine/xylazine combination in acute lung injury induced by α-naphthylthiourea (ANTU). Material and Methods. ANTU was injected intraperitoneally (i.p.) in rats at the dose of 10 mg/kg. Ketamine (15, and 50 mg/kg, i.p.), midazolam (2 and 4 mg/kg, i.p.), and ketamine/xylazine (50/10 mg/kg, i.p.) administered to rats 30 min prior to ANTU. Four hours later, the lung weight/body weight (LW/BW) ratio and pleural effusion (PE) were measured. Histopathological changes were documented in each lung tissue, including intra-alveolar hemorrhage, alveolar edema and inflammation. The severity of the lung injury was scored (0-3). Results. Ketamine, midazolam and ketamine/xylazine had a significant prophylactic effect on pleural effusion formation at all doses and significantly reduced pleural effusion. Ketamine caused a significant reduction of inflammation, hemorrhage and edema scoring and midazolam (2 mg/kg) and ketamine/xylazine caused a significant reduction of inflammation and edema scoring. Conclusions. It can be concluded that ketamine and midazolam may attenuate lung injuries induced by ANTU. In addition to their anesthetic or sedative properties, the prophylactic effects of these agents on lung tissue damage will contribute to the treatment of intensive care unit diseases including acute lung injury. Similarly, the effects of these agents on lung pathophysiology should be considered in experimental applications (Adv Clin Exp Med 2014, 23, 3, 343-351).

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Section: Discussionmentioning

confidence: 99%

“…The exact mechanisms of the effects of ketamine on pleural effusion are still obscure. But these mechanisms might be related to the effects of ketamine on immune/inflammatory cells, ROS and iNOS expression [8,9,[29][30][31]. These mechanisms are also known to play a role in ANTU-mediated damage [6,16,18].…”

Section: Discussionmentioning

confidence: 99%

The Effects of Ketamine, Midazolam and Ketamine/Xylazine on Acute Lung Injury Induced by α-Naphthylthiourea in Rats*

Erdem¹,

Yurdakan²,

Yilmaz-Sipahi³

2014

Adv Clin Exp Med

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“…The day before each experiment, rats were anesthetized with an intramuscular injection of ketamine and xylazine (90 and 9 mg/kg, respectively), and sterile surgery was performed to implant catheters in the carotid artery and jugular vein, as previously described (23,37). Because xylazine can act as an ␣-adrenergic agonist and attenuate the expression of inflammatory genes (24), the animals were returned to individual cages, fasted overnight, and provided water ad libitum. Any confounding effects of xylazine would be expected to have dissipated because the anesthetic has a relatively short half-life in vivo (1,51).…”

Section: Methodsmentioning

confidence: 99%

Epinephrine stimulates IL-6 expression in skeletal muscle and C₂C₁₂myoblasts: role of c-Jun NH₂-terminal kinase and histone deacetylase activity

Frost¹,

Nystrom²,

Lang³

2004

American Journal of Physiology-Endocrinology and Metabolism

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Although an individual's genetic makeup is a major determinant of muscle mass, other influences, such as hormones, cytokines, nutrition, and exercise can also modulate muscle size. IL-6 is an important inflammatory cytokine. Mice that overexpress IL-6 fail to thrive and/or have reduced skeletal muscle mass. The purpose of the present study was to determine whether the stress hormone epinephrine increases inflammatory cytokine expression in skeletal muscle and muscle cells. Infusion of epinephrine in vivo for 2 h increased IL-6 protein (15-fold) and mRNA (40-fold) in skeletal muscle but not in liver. Epinephrine had a similar effect in C2C12 muscle cells, where the hormone increased IL-6 protein and mRNA in a dose- and time-dependent manner. Epinephrine-stimulated IL-6 expression was attenuated by the α-adrenergic receptor antagonist phentolamine and completely blocked by either the β1/2-adrenergic receptor antagonist propranalol or the β2-antagonist ICI-118551. The transcriptional inhibitor DRB and the synthetic glucocorticoid dexamethasone also blocked epinephrine-induced IL-6. SP-600125 (a JNK inhibitor) and SB-202190 (a p38 MAP kinase inhibitor) completely blocked epinephrine-induced IL-6 synthesis. Endotoxin and epinephrine given together had a synergistic affect on IL-6 mRNA and protein expression. Trichostatin A (a histone deacetylase inhibitor) blocked both endotoxin- and epinephrine-induced IL-6 expression. These data suggest that epinephrine induces IL-6 synthesis in skeletal muscle in vivo and myocytes in vitro. Epinephrine utilizes predominantly the β1/2-adrenergic receptors to stimulate IL-6 synthesis. Endotoxin and epinephrine synergize to increase IL-6 mRNA expression. Optimal IL-6 synthesis may require both stress kinase and histone deacetylase activity.

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“…21,22 Additionally, ketamine has been shown to attenuate symptoms of endotoxaemia in alipopolysaccharide (LPS)-induced rat model of sepsis, by reducing NF kappa B activity and TNF-alpha production 23 and diminishing the expression of inducible nitric oxide synthase. 24 In this study, we identified POST as clinical outcome associated with routine surgery that is common and important to avoid. Furthermore, we demonstrated that Ketamine gargle significantly reduces the incidence and severity of POST compared to distilled water gargle, up to 24 hrs.…”

Section: Resultsmentioning

confidence: 99%

Gargling With Ketamine Attenuates Post - Operative Sore Throat

Tejashwini¹,

Jagadish²

2014

jemds

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Ketamine/Xylazine attenuates LPS-induced iNOS expression in various rat tissues

Cited by 33 publications

References 20 publications

The Effects of Ketamine, Midazolam and Ketamine/Xylazine on Acute Lung Injury Induced by α-Naphthylthiourea in Rats*

The Effects of Ketamine, Midazolam and Ketamine/Xylazine on Acute Lung Injury Induced by α-Naphthylthiourea in Rats*

Epinephrine stimulates IL-6 expression in skeletal muscle and C₂C₁₂myoblasts: role of c-Jun NH₂-terminal kinase and histone deacetylase activity

Gargling With Ketamine Attenuates Post - Operative Sore Throat

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Ketamine/Xylazine attenuates LPS-induced iNOS expression in various rat tissues

Cited by 33 publications

References 20 publications

The Effects of Ketamine, Midazolam and Ketamine/Xylazine on Acute Lung Injury Induced by α-Naphthylthiourea in Rats*

The Effects of Ketamine, Midazolam and Ketamine/Xylazine on Acute Lung Injury Induced by α-Naphthylthiourea in Rats*

Epinephrine stimulates IL-6 expression in skeletal muscle and C2C12myoblasts: role of c-Jun NH2-terminal kinase and histone deacetylase activity

Gargling With Ketamine Attenuates Post - Operative Sore Throat

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Epinephrine stimulates IL-6 expression in skeletal muscle and C₂C₁₂myoblasts: role of c-Jun NH₂-terminal kinase and histone deacetylase activity