Protective effect of an intrinsic antioxidant, HMH (5-hydroxy-1-methylhydantoin; NZ-419), against cellular damage of kidney tubules

Ienaga, Kazuharu; Park, Chan Hum; Yokozawa, Takako

doi:10.1016/j.etp.2012.05.001

Cited by 6 publications

(4 citation statements)

References 37 publications

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“…Oxidative stress is a causative factor in this pathology and, particularly, plasma levels of oxidative stress indicators (isoprostanes) were found particularly increased in ACS, compared with stable coronary artery disease (CAD) and correlating with platelet activation (Szuldrzynski et al 2010 ). In mammals, the metabolism of 1-methylhydantoin occurs via 5-hydroxymethylhydantoin, which is an intrinsic antioxidant against cellular damage (Ienaga et al 2013 ). The observed decrease of urinary 1-methylhydantoin in response to an ACS correlates well with an activated metabolism in favor of 5-hydroxymethylhydantoin in response to increased levels of ROS produced by activated platelets.…”

Section: Discussionmentioning

confidence: 99%

KLK1 and ZG16B proteins and arginine–proline metabolism identified as novel targets to monitor atherosclerosis, acute coronary syndrome and recovery

et al. 2014

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We pursued here the identification of specific signatures of proteins and metabolites in urine which respond to atherosclerosis development, acute event and/or recovery. An animal model (rabbit) of atherosclerosis was developed and molecules responding to atherosclerosis silent development were identified. Those molecules were investigated in human urine from patients suffering an acute coronary syndrome (ACS), at onset and discharge. Kallikrein1 (KLK1) and zymogen granule protein16B (ZG16B) proteins, and l-alanine, l-arabitol, scyllo-inositol, 2-hydroxyphenilacetic acid, 3-hydroxybutyric acid and N-acetylneuraminic acid metabolites were found altered in response to atherosclerosis progression and the acute event, composing a molecular panel related to cardiovascular risk. KLK1 and ZG16B together with 3-hydroxybutyric acid, putrescine and 1-methylhydantoin responded at onset but also showed normalized levels at discharge, constituting a molecular panel to monitor recovery. The observed decreased of KLK1 is in alignment with the protective mechanism of the kallikrein–kinin system. The connection between KLK1 and ZG16B shown by pathway analysis explains reduced levels of toll-like receptor 2 described in atherosclerosis. Metabolomic analysis revealed arginine and proline metabolism, glutathione metabolism and degradation of ketone bodies as the three main pathways altered. In conclusion, two novel urinary panels of proteins and metabolites are here for the first time shown related to atherosclerosis, ACS and patient’s recovery.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-014-0761-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

KLK1 and ZG16B proteins and arginine–proline metabolism identified as novel targets to monitor atherosclerosis, acute coronary syndrome and recovery

et al. 2014

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“…LDH leakage is well correlated with cell damage and membrane peroxidation (Ienaga, Park, & Yokozawa, 2012), also was used in the present study to show the resulted damage to cell membrane. Some natural antioxidants could decrease LDH leakage in the H 2 O 2 -injured cells (Hu, Han, Huang, & Wang, 2011).…”

Section: Protective Effects Of the Casein Hydrolysates On Rat Hepatocmentioning

confidence: 99%

In vitrocytoprotection of modified casein hydrolysates by plastein reaction on rat hepatocyte cells

Zhao

Yang

2013

CyTA - Journal of Food

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“…Therefore, protecting kidney function is also an effective treatment for PQ poisoning. Some studies have found that hydantoin derivatives can be used as a treatment for renal failure [17–19], and we have revealed that the 5-hydroxy-1-methylhydantoin (HMH), the analogue of MH, a mammalian creatinine metabolite and an intrinsic antioxidant [17–19], protects against PQ toxicity [20,21]. MH is a metabolite of creatinine formed through deamination by deaminase produced by microorganisms in the gastrointestinal tract [22,23], as shown in Fig 1.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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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.

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Protective effect of an intrinsic antioxidant, HMH (5-hydroxy-1-methylhydantoin; NZ-419), against cellular damage of kidney tubules

Cited by 6 publications

References 37 publications

KLK1 and ZG16B proteins and arginine–proline metabolism identified as novel targets to monitor atherosclerosis, acute coronary syndrome and recovery

KLK1 and ZG16B proteins and arginine–proline metabolism identified as novel targets to monitor atherosclerosis, acute coronary syndrome and recovery

In vitrocytoprotection of modified casein hydrolysates by plastein reaction on rat hepatocyte cells

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

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