Studies on the Precursor of Methylguanidine in Rats with Renal Failure

Yokozawa, Takako; Fujitsuka, Naoki; Oura, Hikokíchi

doi:10.1159/000186384

Cited by 26 publications

(15 citation statements)

References 11 publications

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“…This increase is either due to reduced excretion or due to increased production. Indeed, it has been proposed that in patients with chronic renal failure, an increase in MG production may arise from the conversion of creatinine to MG (Orita et al, 1978;Yokozawa et al, 1990;Yokozawa et al, 1991). Furthermore, Natelson & Sherwin (1979) suggested that urea could be converted to creatine, via canavanine in a supposed 'guanidinic cycle', and subsequently converted in creatinine to be included in the formation of MG.…”

Section: Discussionmentioning

confidence: 99%

Effect of methylguanidine on rat blood pressure: role of endothelial nitric oxide synthase

Sorrentino

Pinto

1995

British J Pharmacology

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The effect of acute i.v. administration of methylguanidine (MG) on mean arterial blood pressure (MABP) was investigated in anaesthetized male Wistar rats. MG (1–30 mg kg−l i.v.) produced an increase in MABP in a dose‐dependent manner both in normal and in hexamethonium (5 mg kg−1, i.v)‐treated rats. L‐Arginine (30 or 150 mg kg−1, i.v.), but not its enantiomer D‐arginine (30 or 150 mg kg−1, i.v.), reversed the effect of MG on MABP in both normal and hexamethonium‐treated rats. L‐Arginine (150 mg kg−1, i.v.) administered 2min before MG (30 mg kg−1, i.v.) prevented the increase in MABP caused by MG in either normal or hexamethonium‐treated rats. This effect was not observed with D‐arginine (150 mg kg−1, i.v.). Thus, the rise in MABP caused by MG in the anaesthetized rat is due to inhibition of endothelial NO‐synthase activity. We speculate that the rise in the plasma concentration of endogenous MG associated with uraemia may contribute to the hypertension seen in patients with chronic renal failure.

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Section: Discussionmentioning

confidence: 99%

Effect of methylguanidine on rat blood pressure: role of endothelial nitric oxide synthase

Sorrentino

Pinto

1995

British J Pharmacology

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“…These tissues (kidney, heart or liver) injury or dysfunction caused by iron–ROS positively interaction underpins the early stage of related pathological symptom. ROS such as hydroxyl radicals and O 2 •− , as well as uremic toxins are mainly responsible for renal failure (Paller et al 1984; Wills 1985; Yokozawa et al 1991). In addition, free radicals play a considerable role in the synthesis of the uremic toxins Cr, MG and GSA (Fujitsuka et al 1994).…”

Section: Introductionmentioning

confidence: 99%

EGCG inhibit chemical reactivity of iron through forming an Ngal–EGCG–iron complex

Bao

et al. 2013

Biometals

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Accumulated evidence indicates that the interconversion of iron between ferric (Fe3+) and ferrous (Fe2+) can be realized through interaction with reactive oxygen species in the Fenton and Haber–Weiss reactions and thereby physiologically effects redox cycling. The imbalance of iron and ROS may eventually cause tissue damage such as renal proximal tubule injury and necrosis. Many approaches were exploited to ameliorate the oxidative stress caused by the imbalance. (−)-Epigallocatechin-3-gallate, the most active and most abundant catechin in tea, was found to be involved in the protection of a spectrum of renal injuries caused by oxidative stress. Most of studies suggested that EGCG works as an antioxidant. In this paper, Multivariate analysis of the LC–MS data of tea extracts and binding assays showed that the tea polyphenol EGCG can form stable complex with iron through the protein Ngal, a biomarker of acute kidney injury. UV–Vis and Luminescence spectrum methods showed that Ngal can inhibit the chemical reactivity of iron and EGCG through forming an Ngal–EGCG–iron complex. In thinking of the interaction of iron and ROS, we proposed that EGCG may work as both antioxidant and Ngal binding siderphore in protection of kidney from injuries.

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“…Whereas nearly 100 different guanidino compounds have been found in the natural world, those found in the serum and urine of patients with renal failure include guanidine, guanidinosuccinic acid, guanidinopropionic acid, guanidinoacetic acid, arginine, creatinine (Cr), creatine, and methylguanidine (MG). Among these compounds, MG has been studied from various aspects in relation to its toxicity [9, 10], quantification [11], precursor [12, 13, 14], organs where it is produced [15, 16, 17], production pathways [18, 19, 20, 21, 22], factors influencing its production [23, 24, 25], etc. However, few studies have examined the specific location of MG production in the kidney and the factors involved in its production.…”

Section: Introductionmentioning

confidence: 99%

Site of Methylguanidine Production and Factors That Influence Production Levels

Yokozawa

Muto

Wakaki

et al. 2002

Nephron

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The site of methylguanidine (MG) production in the kidney was investigated using animal models of renal disease and cultured renal epithelial cells. In rats with proximal tubular injury induced by adenine, the blood and urinary levels of MG increased as the severity of injury increased. In contrast, in cases of glomerular injury, there were no such changes in MG levels. Thus, it was apparent that proximal tubular injury served to promote MG production. In addition, a marked increase was observed in the intensities of bands attributable to 5,5-dimethyl-1-pyrroline-N-oxide (DMPO)-OH in the electron spin resonance spectrum of the kidney in the rats given adenine. In these rats, the activity of the radical-scavenging enzymes superoxide dismutase, catalase, and glutathione peroxidase was decreased. This suggests that the formation of excessive radicals and deterioration of defense mechanisms that contribute to the development of oxidative stress underlie the enhanced MG production. The experiments using cultured cells revealed that an oxide of adenine, 2,8-dihydroxyadenine (DHOA), directly induced renal tubular injury. These findings indicate that the accumulation of creatinine due to DHOA, combined with oxidative stress, resulted in increased MG production.

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Studies on the Precursor of Methylguanidine in Rats with Renal Failure

Cited by 26 publications

References 11 publications

Effect of methylguanidine on rat blood pressure: role of endothelial nitric oxide synthase

Effect of methylguanidine on rat blood pressure: role of endothelial nitric oxide synthase

EGCG inhibit chemical reactivity of iron through forming an Ngal–EGCG–iron complex

Site of Methylguanidine Production and Factors That Influence Production Levels

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