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. 2022 Jan;23(1):e16.
doi: 10.4142/jvs.21188.

Xylazole inhibits NO-cGMP pathway in fetal rat nerve cells

Xinyu Wang  1 , Yue Wu  1 , Lin Liu  1 , Hui Bai  1 , Zhiheng Zhang  1 , Mingchao Zhao  1 , Tianwen Ma  1 , Xiaopeng Song  1 , Lina Jia  1 , Liangyu Lv  1 , Yue Yu  1 , Xinyu Xu  1 , Hong Chen  1 , Li Gao  2
Affiliations

Xylazole inhibits NO-cGMP pathway in fetal rat nerve cells

Xinyu Wang et al. J Vet Sci. 2022 Jan.

Abstract

Background: Xylazole (Xyl) is a veterinary anesthetic that is structurally and functionally similar to xylazine. However, the effects of Xyl in vitro remain unknown.

Objectives: This study aimed to investigate the anesthetic mechanism of Xyl using fetal rat nerve cells treated with Xyl.

Methods: Fetal rat nerve cells cultured for seven days were treated with 10, 20, 30, and 40 μg/ mL Xyl for 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, and 120 min. Variations of amino acid neurotransmitters (AANTs), Nitric oxide-Cyclic GMP (NO-cGMP) signaling pathway, and ATPase were evaluated.

Results: Xyl decreased the levels of cGMP and NO in nerve cells. Furthermore, Xyl affected the AANT content and Na+-K+-ATPase and Ca2+-Mg2+-ATPase activity in nerve cells. These findings suggested that Xyl inhibited the NO-cGMP signaling pathway in nerve cells in vitro.

Conclusions: This study provided new evidence that the anesthetic and analgesic effects of Xyl are related to the inhibition of the NO-cGMP signaling pathway.

Keywords: Xylazole; anesthesia; cyclic GMP; gamma-aminobutyric acid; glutamic acid.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1. Observation of fetal rat cerebral cortex nerve cells cultured in vitro. Observation of fetal rat cerebral cortex nerve cells cultured in vitro for 3 h (A), 3 day (B), 7 day (C) and immunofluorescence staining under the same field of view on the 7th day (D).
Fig. 2
Fig. 2. Effects of different concentrations of Xyl on nerve cell viability. Values were expressed as mean ± SEM.
Xyl, xylazole.
Fig. 3
Fig. 3. Effects of Xyl on the NO-cGMP signaling pathway. (A-E) The NO content; (F-J) The cGMP content. Values were expressed as mean ± SEM.
Xyl, xylazole. *p < 0.05, **p < 0.01 vs. control group; # p < 0.05, ##p < 0.01 vs. xylazine group.
Fig. 4
Fig. 4. Effects of Xyl on the AANTs. (A-E) The GABA content; (F-J) The Glu content; (K-O) The Asp content. Values were expressed as mean ± SEM.
Xyl, xylazole; GABA, γ-aminobutyric acid; AANT, amino acid neurotransmitter. *p < 0.05, **p < 0.01 vs. control group.
Fig. 5
Fig. 5. Effects of Xyl on the ATPase. (A-E) The Na+-K+-ATPase activity; (F-J) The Ca2+-Mg2+-ATPase activity. Values were expressed as mean ± SEM.
Xyl, xylazole. *p < 0.05, **p < 0.01 vs. control group.
See this image and copyright information in PMC

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