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Molecular mechanisms of the sedation and analgesia induced by xylazine on Wistar rats and PC12 cell.

ABSTRACT: In veterinary clinics, xylazine is commonly used as a sedative, analgesic agent that produces muscle relaxation. In this study, we aimed to explore the mechanism of action of xylazine both in vivo and in vitro. After determing the optimal dose of xylazine, 35 male Wistar rats were divided into seven groups (n=5 per group), including a control group (saline) and xylazine administration groups. Then, at six time points after xylazine administration indicators were evaluated for changes. Moreover, PC12 cells were co-cultured with xylazine, and extracellular regulated protein kinase (ERK) siRNA and protein kinase A (PKA) siRNA were transfected into cells to identify changes of relevant indicators. Our data showed that xylazine influenced the level of adenosine triphosphate (ATP) ase and cyclic adenosine monophosphate (cAMP), and regulated the expression of GluR1, ERK, PKA, cAMP-response element binding protein (CREB), and brain derived neurotrophic factor (BDNF) in the nervous system. However, xylazine did not significantly affect the expression of GluR2 and protein kinase C (PKC). Together, these results indicated that xylazine might exert sedation and analgesia by regulating the PKA/ERK/CREB signaling pathway.

SUBMITTER: Zhao J

PROVIDER: S-EPMC6699970 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Molecular mechanisms of the sedation and analgesia induced by xylazine on Wistar rats and PC12 cell.

Zhao Jinghua J Zhang Yiming Y Liu Wenhan W Chen Yu Y Chang Daiyue D Zhang Xintong X Chang Tian T Wang Qi Q Liu Tao T Gao Li L

Experimental animals 20190408 3

In veterinary clinics, xylazine is commonly used as a sedative, analgesic agent that produces muscle relaxation. In this study, we aimed to explore the mechanism of action of xylazine both in vivo and in vitro. After determing the optimal dose of xylazine, 35 male Wistar rats were divided into seven groups (n=5 per group), including a control group (saline) and xylazine administration groups. Then, at six time points after xylazine administration indicators were evaluated for changes. Moreover, ...[more]

PMID: 30956255

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Project description:ObjectivesTo explore the effect of ketamine-xylazine anesthesia on light-induced retinal degeneration in rats.MethodsRats were anesthetized with ketamine and xylazine (100 and 5 mg, respectively) for 1 h, followed by a recovery phase of 2 h before exposure to 16,000 lux of environmental illumination for 2 h. Functional assessment by electroretinography (ERG) and morphological assessment by in vivo imaging (optical coherence tomography), histology (hematoxylin/eosin staining, TUNEL assay) and immunohistochemistry (GFAP and rhodopsin staining) were performed at baseline (ERG), 36 h, 7 d and 14 d post-treatment. Non-anesthetized animals treated with light damage served as controls.ResultsKetamine-xylazine pre-treatment preserved retinal function and protected against light-induced retinal degeneration. In vivo retinal imaging demonstrated a significant increase of outer nuclear layer (ONL) thickness in the non-anesthetized group at 36 h (p<0.01) and significant reduction one week (p<0.01) after light damage. In contrast, ketamine-xylazine pre-treated animals showed no significant alteration of total retinal or ONL thickness at either time point (p>0.05), indicating a stabilizing and/or protective effect with regard to phototoxicity. Histology confirmed light-induced photoreceptor cell death and Müller cells gliosis in non-anesthetized rats, especially in the superior hemiretina, while ketamine-xylazine treated rats showed reduced photoreceptor cell death (TUNEL staining: p<0.001 after 7 d), thicker ONL and longer IS/OS. Fourteen days after light damage, a reduction of standard flash induced a-wave amplitudes and a-wave slopes (p = 0.01) and significant alterations in parameters of the scotopic sensitivity function (e.g. Vmax of the Naka Rushton fit p = 0.03) were observed in non-treated vs. ketamine-xylazine treated animals.ConclusionsOur results suggest that pre-treatment with ketamine-xylazine anesthesia protects retinas against light damage, reducing photoreceptor cell death. These data support the notion that anesthesia with ketamine-xylazine provides neuroprotective effects in light-induced cell damage.

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Molecular mechanisms of the sedation and analgesia induced by xylazine on Wistar rats and PC12 cell.

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Molecular mechanisms of the sedation and analgesia induced by xylazine on Wistar rats and PC12 cell.

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