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

ABSTRACT: 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-? 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-? 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-? 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-? content between the PQ group and MH group (all p<0.05). MH decreased the production of malondialdehyde and TNF-? 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.

SUBMITTER: Liu B

PROVIDER: S-EPMC6764654 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Liu Bo B Chen Annan A Lan Jinyi J Ren Lei L Wei Yifan Y Gao Lina L

PloS one 20190927 9

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 w ...[more]

PMID: 31560695

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Project description:Paraquat (PQ) is a non-selective herbicide and is exceedingly toxic to humans. The mechanism of PQ toxicity is very complex and has not been clearly defined. There is no specific antidote for PQ poisoning. 5-hydroxy-1-methylhydantoin (HMH) is an intrinsic antioxidant and can protect against renal damage caused by PQ. The mechanism of PQ toxicology and the possible effects of HMH on PQ-induced lung injury were determined in this study. It was found that PQ decreased superoxide dismutase (SOD) activity and elevated the level of malondialdehyde (MDA), while HMH elevated SOD activity and decreased the level of MDA. Based on metabolomics, the citrate cycle, glutathione metabolism, taurine and hypotaurine metabolism, regulation of lipolysis in adipocytes, inflammatory mediator regulation of TRP channels, purine and pyrimidine metabolism, aldosterone synthesis and secretion, and phenylalanine metabolism were changed in the PQ group. Compared with the PQ group, the levels of N-acetyl-l-aspartic acid, L-glutamic acid, L-aspartic acid, mesaconic acid, adenosine 5' monophosphate, methylmalonic acid, cytidine, phosphonoacetic acid, hypotaurine, glutathione (reduced) and cysteinylglycine increased, while the levels of corticosterone, xanthine, citric acid, prostaglandin G2, 4-pyridoxic acid and succinyl proline decreased in the HMH group. These metabolites revealed that HMH can alleviate inflammation caused by PQ and elevate the activity of intrinsic antioxidants. In conclusion, our results revealed PQ toxicology and the pharmacology underlying the protective effect of HMH on lung injury due to PQ. Toxicity caused by PQ results in lipid peroxidation and an increase in reactive oxygen species (ROS), nitric oxide (NO), damage to the biliary system, gastrointestinal system and nervous system, in addition to lungs, kidneys, and the liver. HMH is a good antioxidant and protects against lung injury caused by PQ. In summary, HMH efficiently reduced PQ-induced lung injury in mice.

Project description:ObjectiveThe chest computed tomography (CT) examination is an important clinical examination in the diagnosis and monitoring of paraquat- (PQ-) induced lung injury. The aim of this study was to explore the prognostic value of the average lung CT number acquired by quantitative CT techniques in patients with acute paraquat poisoning in the early stages of the disease.Methods46 patients who suffered from acute PQ poisoning in the emergency department of the Nanjing Drum Tower Hospital from January 2015 to June 2020 were enrolled in the present study. The patients were divided into survival group (n = 21) and nonsurvival group (n = 25). Clinical data were collected from subjects who met the inclusion criteria, including general information, personal disease history, and laboratory test indicators. The average lung CT numbers of each patient were obtained by quantitative CT techniques. Receiver operating characteristic (ROC) analysis was conducted to assess the prognostic value of average lung CT number in patients with acute paraquat poisoning.ResultsThe average CT numbers of the middle-lung, lower-lung, and whole lung fields in the nonsurvival group were significantly higher than those of the survival group (p < 0.0001). However, the upper-lung field was not significantly different between the two groups (p = 0.7765). The AUCs of different levels ranged from 0.554 to 0.977, among which the lower-lung field presented the largest AUC of 0.977 (95% CI: 0.943∼1; cut-off value: -702Hu; sensitivity 96%; specificity, 90.5%; YI: 0.865), followed by the whole lung field 0.914 (95% CI: 0.830∼0.999; cut-off value: -727Hu; sensitivity 76%; specificity, 95.2%; YI: 0.712) and the middle-lung field 0.87 (95% CI: 0.768∼0.971; cut-off value: -779Hu; sensitivity 80%; specificity, 85.7%; YI: 0.657).ConclusionThe present study indicated that the average lung CT number could be used to evaluate the relationship between the severity of PQ-induced lung injury and prognosis, especially in the lower-lung field. However, further research is needed to draw a clear conclusion.

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

Publications

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

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