Abstract | OBJECTIVE: METHODS: Adult male Sprague-Dawley rats were exposed to 400 ppm Cl2 for 5 min. The histopathological examination was carried out and intracellular reactive oxygen species (ROS) levels were measured by the confocal laser scanning system. Subsequently, to evaluate the effect of PTX, a dose of 100 mg/kg was administered. The activities of superoxide dismutase (SOD) and the contents of malondialdehyde (MDA), glutathione (GSH), oxidized glutathione ( GSSG) and lactate dehydrogenase (LDH) were determined by using commercial kits according to the manufacturer's instructions. Western blot assay was used to detect the protein expressions of SOD1, SOD2, catalase (CAT), hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor ( VEGF), occludin, E-cadherin, bcl-xl, LC 3, Beclin 1, PTEN-induced putative kinase 1 (PINK 1) and Parkin. RESULTS: The histopathological examination demonstrated that chlorine could destroy the lung structure with hemorrhage, alveolar collapse, and inflammatory infiltration. ROS accumulation was significantly higher in the lungs of rats suffering from inhaling chlorine (P<0.05). PTX markedly reduced concentrations of MAD and GSSG, while increased GSH (P<0.05). The protein expression levels of SOD1 and CAT also decreased (P<0.05). Furthermore, the activity of LDH in rats treated with PTX was significantly decreased compared to those of non-treated group (P<0.05). Additionally, the results also showed that PTX exerted an inhibition effect on protein expressions of HIF-1α, VEGF and occludin, and increased the level of E-cadherin (P<0.05). While the up-regulation of Beclin 1, LC 3II/I, Bcl-xl, and Parkin both in the lung tissues and mitochondria, were found in PTX treated rats (P<0.05). The other protein levels were decreased when treated with PTX (P<0.05). CONCLUSION: PTX could ameliorate chlorine-induced lung injury via inhibition effects on oxidative stress, hypoxia and autophagy, thus suggesting that PTX could serve as a potential therapeutic approach for ALI.
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Authors | Meng-Meng Liu, Jiang-Zheng Liu, Chen-Qian Zhao, Peng Guo, Zhao Wang, Hao Wu, Weihua Yu, Rui Liu, Chun-Xu Hai, Xiao-di Zhang |
Journal | BMC pharmacology & toxicology
(BMC Pharmacol Toxicol)
Vol. 24
Issue 1
Pg. 12
(02 27 2023)
ISSN: 2050-6511 [Electronic] England |
PMID | 36850013
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2023. The Author(s). |
Chemical References |
- Chlorine
- Pentoxifylline
- Vascular Endothelial Growth Factor A
- Glutathione Disulfide
- Beclin-1
- Occludin
- Reactive Oxygen Species
- Superoxide Dismutase-1
- Glutathione
- Ubiquitin-Protein Ligases
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Topics |
- Rats
- Adult
- Humans
- Animals
- Male
- Rats, Sprague-Dawley
- Chlorine
- Pentoxifylline
(pharmacology, therapeutic use)
- Vascular Endothelial Growth Factor A
- Glutathione Disulfide
- Beclin-1
- Occludin
- Reactive Oxygen Species
- Superoxide Dismutase-1
- Acute Lung Injury
(chemically induced, drug therapy, prevention & control)
- Glutathione
- Hypoxia
- Ubiquitin-Protein Ligases
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