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Protective effects of pentoxifylline against chlorine-induced acute lung injury in rats.
- Source :
-
BMC pharmacology & toxicology [BMC Pharmacol Toxicol] 2023 Feb 27; Vol. 24 (1), pp. 12. Date of Electronic Publication: 2023 Feb 27. - Publication Year :
- 2023
-
Abstract
- Objective: Chlorine is a chemical threat agent that can be harmful to humans. Inhalation of high levels of chlorine can lead to acute lung injury (ALI). Currently, there is no satisfactory treatment, and effective antidote is urgently needed. Pentoxifylline (PTX), a methylxanthine derivative and nonspecific phosphodiesterase inhibitor, is widely used for the treatment of vascular disorders. The present study was aimed to investigate the inhibitory effects of PTX on chlorine-induced ALI in rats.<br />Methods: Adult male Sprague-Dawley rats were exposed to 400 ppm Cl <subscript>2</subscript> 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.<br />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).<br />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.<br /> (© 2023. The Author(s).)
- Subjects :
- Rats
Adult
Humans
Animals
Male
Rats, Sprague-Dawley
Chlorine
Vascular Endothelial Growth Factor A
Glutathione Disulfide
Beclin-1
Occludin
Reactive Oxygen Species
Superoxide Dismutase-1
Glutathione
Hypoxia
Ubiquitin-Protein Ligases
Pentoxifylline pharmacology
Pentoxifylline therapeutic use
Acute Lung Injury chemically induced
Acute Lung Injury drug therapy
Acute Lung Injury prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 2050-6511
- Volume :
- 24
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC pharmacology & toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 36850013
- Full Text :
- https://doi.org/10.1186/s40360-023-00645-2