Role of Reactive Oxygen and Argininosuccinate
in Guanidinosuccinate Synthesis in Isolated Rat
Hepatocytes

Aoyagi, Kazumasa; Nagase, Sohji; Gotoh, Michihiro; Akiyama, Kayo; Satoh, Makiko; Hirayama, Aki; Kôyama, Akio

doi:10.1159/000468630

Cited by 13 publications

(7 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Generation of reactive oxygen was proposed as a crucial step also in dexamethasone‐induced apoptosis [36]. In the present work, DMSO, a hydroxy radical scavenger [37, 38], slightly suppressed RT‐induced apoptosis (Fig. 3A), suggesting the involvement of reactive oxygen in RT‐induced apoptosis.…”

Section: Discussionsupporting

confidence: 65%

Characterization of room temperature induced apoptosis in HL‐60

et al. 1997

View full text Add to dashboard Cite

We found that exposure to room temperature (RT/ 21 °C) causes apoptosis in HL-60 cells. Here we characterized RT-induced apoptosis in HL-60. After exposure to RT, apoptosis starts within 6 h and more than 80% of the cells underwent apoptosis within 20 h. All cells, however, were committed to apoptosis after 16 h and no viable cells could be recovered. The caspase-1 inhibitor (YVAD-CHO) effectively blocked apoptosis, whereas the caspase-3 inhibitor (DEVD-CHO) did not. About 20% of newly obtained early passage HL-60 cells (passage 10) also underwent apoptosis by RT treatment. These data suggest that some population in HL-60 which responds to RT with apoptosis became dominant during passaging.

show abstract

Section: Discussionsupporting

confidence: 65%

Characterization of room temperature induced apoptosis in HL‐60

et al. 1997

View full text Add to dashboard Cite

show abstract

“…Reactive oxygen species, such as hydroxyl radicals and O 2 - , as well as uremic toxins are also mainly responsible for renal failure ( − ). In addition, free radicals play a considerable role in the synthesis of the uremic toxins Cr, MG and GSA ( − ). In light of these reports and our present results, green tea polyphenol would be expected to play a crucial role as a scavenger of free radicals and inhibitor of uremic toxin synthesis, thereby eventually ameliorating renal failure.…”

Section: Discussionmentioning

confidence: 99%

Influence of Green Tea Polyphenol in Rats with Arginine-Induced Renal Failure

Yokozawa¹,

Cho²,

Nakagawa³

2003

J. Agric. Food Chem.

View full text Add to dashboard Cite

To determine whether green tea polyphenol ameliorates the pathological conditions induced by excessive dietary arginine, green tea polyphenol was administered to rats at a daily dose of 50 or 100 mg/kg body weight for 30 days with a 2% w/w arginine diet. In arginine-fed control rats, urinary and/or serum levels of guanidino compounds, nitric oxide (NO), urea, protein, and glucose increased significantly, while the renal activities of the oxygen species-scavenging enzymes superoxide dismutase (SOD) and catalase decreased, compared with casein-fed rats. However, rats given green tea polyphenol showed significant and dose-dependent decreases in serum levels of creatinine (Cr) and urea nitrogen and urinary excretion of Cr, and they exerted a slight reduction of nitrite plus nitrate, indicating that green tea polyphenol reduced the production of uremic toxins and NO. In addition, in arginine-fed rats the urinary urea, protein, and glucose level increases were reversed by the administration of green tea polyphenol. Moreover, in rats given green tea polyphenol the SOD and catalase activities suppressed by excessive arginine administration increased dose-dependently, implying the biological defense system was augmented as a result of free radical scavenging. These results suggest that green tea polyphenol would ameliorate renal failure induced by excessive dietary arginine by decreasing uremic toxin, and NO production and increasing radical-scavenging enzyme activity.

show abstract

“…GSA arises from the oxidation of argininosuccinate in the presence of free hydroxyl and superoxide radicals. 94,95 GSA is not only a uremic toxin increased in states of nitrogen retention, such as renal failure, but in addition, together with other guanidino compounds accused to contribute to the (neuro)toxicity in ASA. Interestingly, but not yet studied in human UCD patients, concentrations of GSA in both serum and urine decline sharply in animals and humans exposed to methionine 96 and this could be a therapeutic alternative.…”

Section: Argininosuccinate and Guanidinosuccinic Acid Toxicitymentioning

confidence: 99%

“…GSA arises from the oxidation of argininosuccinate in the presence of free hydroxyl and superoxide radicals . GSA is not only a uremic toxin increased in states of nitrogen retention, such as renal failure, but in addition, together with other guanidino compounds accused to contribute to the (neuro)toxicity in ASA.…”

Section: Pathophysiologymentioning

confidence: 99%

Argininosuccinic aciduria: Recent pathophysiological insights and therapeutic prospects

Baruteau

Dı́ez-Fernández

Lerner³

et al. 2019

J of Inher Metab Disea

View full text Add to dashboard Cite

The first patients affected by argininosuccinic aciduria (ASA) were reported 60 years ago. The clinical presentation was initially described as similar to other urea cycle defects, but increasing evidence has shown overtime an atypical systemic phenotype with a paradoxical observation, that is, a higher rate of neurological complications contrasting with a lower rate of hyperammonaemic episodes. The disappointing long-term clinical outcomes of many of the patients have challenged the current standard of care and therapeutic strategy, which aims to normalize plasma ammonia and arginine levels. Interrogations have raised about the benefit of newborn screening or liver transplantation on the neurological phenotype. Over the last decade, novel discoveries enabled by the generation of new transgenic argininosuccinate lyase (ASL)-deficient mouse models have been achieved, such as, a better understanding of ASL and its close interaction with nitric oxide metabolism, ASL physiological role outside the liver, and the pathophysiological role of oxidative/nitrosative stress or excessive arginine treatment. Here, we present a collaborative review, which highlights these recent discoveries and novel emerging concepts about ASL role in human physiology, ASA clinical phenotype and geographic prevalence, limits of current standard of care and newborn screening, pathophysiology of the disease, and emerging novel therapies. We propose recommendations for monitoring of ASA patients. Ongoing research aims to better understand the underlying pathogenic mechanisms of the systemic disease to design novel therapies.Carmen Diez-Fernandez and Shaul Lerner contributed equally to this study.

show abstract

Role of Reactive Oxygen and Argininosuccinate in Guanidinosuccinate Synthesis in Isolated Rat Hepatocytes

Cited by 13 publications

References 9 publications

Characterization of room temperature induced apoptosis in HL‐60

Characterization of room temperature induced apoptosis in HL‐60

Influence of Green Tea Polyphenol in Rats with Arginine-Induced Renal Failure

Argininosuccinic aciduria: Recent pathophysiological insights and therapeutic prospects

Contact Info

Product

Resources

About