Protective effect and mechanisms of neostigmine in combination with anisodamine against pulmonary oxygen toxicity
10.12206/j.issn.2097-2024.202310049
- VernacularTitle:新斯的明与山莨菪碱联合应用对肺型氧中毒的保护作用及其机制的研究
- Author:
Guangyu ZHANG
1
;
Jing DU
2
;
Mengzhen LIU
1
;
Danni ZHU
1
;
Hui YAN
1
;
Chong LIU
1
Author Information
1. School of Pharmacy, Naval Medical University, Shanghai 200433, China.
2. School of Pharmacy, Jining Medical University, Jining 276826, China.
- Publication Type:Originalarticles
- Keywords:
hyperbaric oxygen;
pulmonary oxygen toxicity;
neoscopolamine;
inflammation;
oxidative stress
- From:
Journal of Pharmaceutical Practice and Service
2024;42(10):433-438
- CountryChina
- Language:Chinese
-
Abstract:
Objective Pulmonary oxygen poisoning resulting from hyperbaric oxygen, frequently occurs in specialized operations, without any current effective prevention or treatment measures. To elucidate the impact and mechanism of neostigmine （NEO） in combination with anisodamine （ANI） （neoscopolamine） on pulmonary oxygen toxicity. Methods The animal model of pulmonary oxygen poisoning was established. C57BL/6 mice were exposed to 2.5 ATA 99.9% oxygen for 6 h. The control group mice were injected with normal saline ip, while the treatment group mice received injections of ANI （25 mg/kg, ip）and NEO （50 μg/kg, ip）. Lung tissues were collected and stained with HE to observe any pathological injuries after exposure. Evans blue stain was utilized to identify lung permeability, wet/dry lung ratio, and protein concentration in the bronchoalveolar lavage fluid （BALF） to assess the lung injury’s severity. The modifications in inflammatory factors, oxidative stress indicators, and iron content in lung tissue were assessed. Results The results showed that the 2.5 ATA 99.9% oxygen-exposed group experienced a significant worsening of lung injury, as well as increased lung permeability, lung wet/dry ratio, and protein content in alveolar lavage fluid when compared to the control group. Moreover, mRNA levels of pro-inflammatory cytokines IL-1β, IL-6, TNF-α, and IFN-γ in the lung tissue of the model group were significantly elevated, while the levels of anti-inflammatory cytokines IL-4 and TGF-β were significantly reduced. The oxidative index MDA also significantly increased, while the antioxidant index GSH significantly decreased. Additionally, the expression of GPX4, a marker of ferroptosis, increased with an increase in iron content. Neoscopolamine treatment successfully reversed those effects. Conclusion The combined use of ANI and NEO had a protective effect on pulmonary oxygen poisoning. Neoscopolamine may inhibit inflammation and oxidative stress by activating the cholinergic anti-inflammatory pathway, thereby reducing the content of free iron in lung tissue and finally inhibiting cell ferroptosis.
