Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Chlorobenzoxime inhibits respiratory syncytial virus infection in neonatal rats via up-regulation of IFN-γ in dendritic cells

Junzhao Li¹, Yonghai Zhang² , Hongmei Qiao³, Yingji Jin¹, Jianmin Wang¹, Binghua Yao¹

¹Department of Pediatrics; ²Department of Neurosurgery, Jiangsu Taizhou People's Hospital, Taizhou, Jiangsu 225300; ³Department of Pediatrics, The First Affiliated hospital of Jilin University, Changchun, Jilin 130061, China.

For correspondence:- Yonghai Zhang Email: AndresHillnty@yahoo.com Tel:+8652389890319

Accepted: 21 January 2020 Published: 29 February 2020

Citation: Li J, Zhang Y, Qiao H, Jin Y, Wang J, Yao B. Chlorobenzoxime inhibits respiratory syncytial virus infection in neonatal rats via up-regulation of IFN-γ in dendritic cells. Trop J Pharm Res 2020; 19(2):239-246 doi: 10.4314/tjpr.v19i2.4

© 2020 The authors.
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Abstract

Purpose: To investigate the effect of chlorobenzoxime on respiratory syncytial virus (RSV) infection in vitro in lung alveolar cells and in vivo in neonatal rats, as well as the mechanism of action involved.

Methods: RSV infection in neonatal rats was induced via intranasal administration of 2 x 106PFU viral particles. Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting were used for determination of changes in interleukin expression.

Results: RSV infection in BEAS-2B cells caused significant reduction in viability and marked alteration in morphological appearance (p < 0.05). Exposure of RSV-infected BEAS-2B cells to chlorobenzoxime prevented viability reduction and changes in morphology, and led to reductions in RSV-mediated increases in levels of interleukin-6 and interleukin-8. Moreover, RSV infection significantly enhanced ROS levels in BEAS-2B cells, when compared to control cells (p < 0.05). Chlorobenzoxime at a concentration of 30 µM completely suppressed RSV-mediated generation of ROS in BEAS-2B cells. In neonatal rats, RSV-induced upregulation of interleukin-4, interleukin-13 and TNF-α, were suppressed in bronchoalveolar lavage fluid (BALF) and lung tissues by chlorobenzoxime. Moreover, the RSV-mediated reduction in IFN-γ was maximally blocked by chlorobenzoxime at a dose of 10 mg/mL. Chlorobenzoxime enhanced the proportion of IFN-γ -producing cells in neonatal rat BALF.

Conclusion: Chlorobenzoxime exhibits antiviral against RSV infection in neonatal rats via increase in dendritic cell population, leading to inhibition of cytokine production. Therefore, chlorobenzoxime is a potential therapeutic agent for RSV infection.

Keywords: Respiratory syncytial virus, Cytokines, Dendritic cells, Lung aveolar cells, Morphology, Interleukins