Chitosan-gentamicin conjugate attenuates heat stress-induced intestinal barrier injury via the TLR4/STAT6/MYLK signaling pathway: In vitro and in vivo studies

Xueting Niu; Canying Hu; Shengwei Chen; Jiaying Wen; Xiaoxi Liu; Yanhong Yong; Zhichao Yu; Xingbin Ma; Chengpeng Li; Mohamad Warda; A M Abd El-Aty; Ravi Gooneratne; Xianghong Ju

doi:10.1016/j.carbpol.2023.121279

Chitosan-gentamicin conjugate attenuates heat stress-induced intestinal barrier injury via the TLR4/STAT6/MYLK signaling pathway: In vitro and in vivo studies

Carbohydr Polym. 2023 Dec 1:321:121279. doi: 10.1016/j.carbpol.2023.121279. Epub 2023 Aug 9.

Authors

Affiliations

¹ College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang 524088, China; Marine Medical Research and Development Centre, Shenzheng Institute of Guangdong Ocean University, Shenzheng 518120, China.
² College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang 524088, China.
³ College of Chemistry and Environment Science, Guangdong Ocean University, Zhanjiang 524088, China.
⁴ Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt.
⁵ Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, 12211 Giza, Egypt; Department of Medical Pharmacology, Medical Faculty, Ataturk University, Erzurum 25240, Turkey.
⁶ Faculty of Agriculture and Life Sciences, Lincoln University, Lincoln 7647, New Zealand.
⁷ College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang 524088, China; Marine Medical Research and Development Centre, Shenzheng Institute of Guangdong Ocean University, Shenzheng 518120, China. Electronic address: juxh77@163.com.

PMID: 37739521
DOI: 10.1016/j.carbpol.2023.121279

Abstract

Heat stress (HS) has a negative impact on animal health. A modified chitosan-gentamicin conjugate (CS-GT) was prepared to investigate its potential protective effects and mechanism of action on heat stress-induced intestinal mucosa injury in IPEC-J2 cells and mouse 3D intestinal organs in a mouse model. CS-GT significantly (P < 0.01) reversed the decline in transmembrane resistance and increased the FITC-dextran permeability of the IPEC-J2 monolayer fusion epithelium caused by heat stress. Heat stress decreased the expression of the tight binding proteins occludin, claudin1, and claudin2. However, pretreatment with CS-GT significantly increased (P < 0.01) the expression of these tight binding proteins. Mechanistically, CS-GT inhibited the activation of the TLR4/STAT6/MYLK signaling pathway induced by heat stress. Molecular docking showed that CS-GT can bind effectively with TLR4. In conclusion, CS-GT alleviates heat stress-induced intestinal mucosal damage both in vitro and in vivo. This effect is mediated, at least partly, by the inhibition of the TLR4/STAT6/MYLK signaling pathway and upregulation of tight junction proteins. These findings suggest that CS-GT may have therapeutic potential in the prevention and treatment of heat stress-related intestinal injury.

Keywords: CS-GT; Heat stress; Intestinal barrier injury; TLR4/STAT6/MYLK.

MeSH terms

Animals
Burns*
Chitosan* / pharmacology
Gentamicins
Mice
Molecular Docking Simulation
Signal Transduction
Toll-Like Receptor 4

Substances

Chitosan
Toll-Like Receptor 4
Gentamicins