Protective mechanism of 1-methylhydantoin against lung injury induced by paraquat poisoning


Autoři: Bo Liu aff001;  Annan Chen aff001;  Jinyi Lan aff001;  Lei Ren aff001;  Yifan Wei aff002;  Lina Gao aff003
Působiště autorů: The 3 Clinical Department of China Medical University, Shenyang, Liaoning, China aff001;  School of Public Health, China Medical University, Shenyang, Liaoning, China aff002;  School of Forensic Medicine, China Medical University, Shenyang, Liaoning,China aff003
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222521

Souhrn

Paraquat (PQ), one of the most widely used herbicides worldwide, causes severe toxic effects in humans and animals. 1-methylhydantoin (MH) is an active ingredient of Ranae Oviductus, which has broad pharmacological activities, e.g., eliminating reactive oxygen species and inhibiting inflammation. This study investigated the effects of MH on lung injury induced by PQ. A PQ poisoning model was established by intragastric infusion of PQ (25 mg/kg), and the control group was simultaneously gavaged with the same dose of saline. The MH group was intraperitoneally injected with 100 mg/kg once per day after intragastric infusion of PQ (25 mg/kg) for five consecutive days. All animals were sacrificed on the sixth day, and the lung tissues were dissected for metabolomics analysis. The lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD) activity, TNF-α and malondialdehyde (MDA) content were determined according to the instructions of the detection kit. Compared with that in the control group, the content of LDH, TNF-α and MDA in the lung tissue of the PQ group was significantly higher, and the activity of SOD in the lung tissue was significantly lower (all p<0.05). Compared with that in the control group, the content of LDH, TNF-α and MDA in the MH group was significantly higher, and the activity of SOD was significantly lower (all p<0.05). However, the differences in SOD activity, LDH activity between the PQ and MH groups were not statistically significant (all p > 0.05). There were significant differences in MDA and TNF-α content between the PQ group and MH group (all p<0.05). MH decreased the production of malondialdehyde and TNF-α to protect against the lung injury caused by PQ poisoning, but it had no significant effect on the activity of LDH and SOD. There were significant differences in metabolomics between the MH group and the PQ poisoning group, primarily in bile acid biosynthesis and metabolism of cholesterol, nicotinate, nicotinamide, alanine, aspartate, glutamate, glycine, threonine, serine, phenylalanine and histidine. Therefore, this study highlights that MH has non-invasive mechanisms and may be a promising tool to treat lung injury induced by PQ poisoning.

Klíčová slova:

Drug metabolism – Inflammation – Metabolic pathways – Metabolites – Poisoning – Superoxide dismutase – Nicotine – Protein metabolism


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PLOS One


2019 Číslo 9

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