Disease relevance of METHYLGUANIDINE

• This study has therefore compared the effects of aminoguanidine with the effects of two other inhibitors of NOS, L-NAME and methylguanidine, on the development of experimental diabetic nephropathy [1].
• L-NAME and methylguanidine did not retard the development of albuminuria, nor did they prevent increases in renal AGE levels, as assessed by fluorescence [1].
• After incubation of whole blood in the presence of methylguanidine, the Escherichia coli stimulated oxidative burst activity of the granulocyte population was significantly inhibited (P < 0.05) [2].
• N-Nitrosocimetidine (NCM) is a derivative of the drug cimetidine, a methylguanidine derivative used in the treatment of peptic ulcer, and is known to be inactive as a complete mouse skin carcinogen, even when given in repeated high doses for a long period [3].
• Cytochrome P-450-dependent N-demethylation of methylguanidine, a uremia toxin, was investigated [4].

High impact information on METHYLGUANIDINE

• This study was undertaken to compare the ability of two guanidine compounds (aminoguanidine and methylguanidine), with different in vitro effects on NO synthase activity and AGE formation, to inhibit diabetic vascular dysfunction developing early after the onset of diabetes [5].
• AG (10(-5) to 3x10(-3) mol/L) and MG (10(-5) to 3x10(-3) mol/L) produced endothelium-independent contractions (E(max)=44.3+/-8.8% and 45.7+/-5.8% of the response to 100 mmol/L KCl, respectively) [6].
• OBJECTIVE--To examine the serum levels of methylguanidine in IDDM children and compare them with markers for glycemic control [7].
• The PMA-stimulated chemiluminescence production of the calcitriol differentiated HL-60 cells was inhibited by the presence of methylguanidine (P < 0.05), guanidinoacetic acid (P < 0.05) and guanidinosuccinic acid (P < 0.05) [2].
• Oxidized markers, dityrosine, methylguanidine, and phosphatidylcholine hydroperoxide, and inflammatory markers, interleukin 6 (IL-6), and C-reactive protein (CRP) were determined [8].

Chemical compound and disease context of METHYLGUANIDINE

• Comparison of renal effects of creatinine, creatol and methylguanidine in rats with adenine-induced chronic renal failure [9].
• (1)Plasma and urinary levels of methylguanidine, guanidinosuccinic acid and guanidinoacetic acid were measured in normal subjects and in patients with renal failure [10].
• For example, we have reported that certain species of reactive oxygen, particularly the hydroxyl radical, play an important role in the biosynthesis of methylguanidine which contributes to toxicity in patients with uremia [11].
• When substances retained in renal failure were added to the incubation mixture a marked inhibition took place with guanidinosuccinic acid, methylguanidine and fraction containing peptides with a molecular weight between 1200-1400 present in uraemic serum and normal urine, but not in serum from patients without renal failure [12].
• Toxicity arising from guanidine compounds: role of methylguanidine as a uremic toxin [13].

Biological context of METHYLGUANIDINE

• Effect of methylguanidine on rat blood pressure: role of endothelial nitric oxide synthase [14].
• The addition of guandine, methylguanidine, or ethylguanidine to R127A increases the kcat for hydrolysis of Bz-gly(o)phe by 10(2) without changing the Km [15].
• However, the accumulation of the toxic guanidino compounds, guanidinosuccinic acid and methylguanidine, corresponded inversely with circulating arginine concentration, possibly reflecting a higher oxidative stress under hypoargininemic conditions [16].
• DNA damage, DNA repair and chromosome aberrations of xeroderma pigmentosum cells and controls following exposure to nitrosation products of methylguanidine [17].
• CTN, MG and GSA concentration dependently blocked GABA-evoked current with calculated IC50 values (+/-SE) of 9.6 +/- 0.9, 9.7 +/- 1.5 and 5.1 +/- 0.4 mM, respectively [18].

Anatomical context of METHYLGUANIDINE

• Guanidinosuccinic acid, creatinine, guanidine, and methylguanidine are substantially increased in the plasma and erythrocytes of the uremic patient [19].
• However, the brain/serum concentration ratios of GSA and of MG were significantly lower in 21-day-old mice than in 7-day-old ones, indicating that at least part of the difference in brain level can be explained by higher permeability of the immature blood-brain barrier to these uremic guanidino compounds [20].
• Sustained increase of methylguanidine in rats after amygdala or hippocampal kindling [21].
• Our data show that methylguanidine, given intraperitoneally at the dose of 30 mg/kg, inhibits the inflammatory response reducing significantly (P<0.05) paw swelling, pleural exudates formation, mononuclear cell infiltration and histological injury [22].
• Nitrosation of methylguanidine (MG) led to products that caused DNA fragmentation (shift in sedimentation profiles of velocity centrifugation through alkaline sucrose gradients), a DNA repair synthesis (unscheduled uptake of (3H]TdR), chromosome aberrations and a lethal effect of cultured human fibroblasts [17].

Associations of METHYLGUANIDINE with other chemical compounds

• L-Arginine (10(-3) mol/L) prevented the contractions by L-NMMA and ADMA but did not change contractions induced by AG and MG [6].
• Brain guanidino compounds, taurocyamine, N-acetylarginine, and methylguanidine were not detected in CSF [23].
• Furthermore, the elevations in the plasma urea nitrogen and creatinine (Cr) levels and the urinary methylguanidine/Cr ratio induced by the procedure were attenuated markedly after oral administration of ECg, implying amelioration of renal impairment [24].
• Grayanotoxin I did not drastically the resting permeability ratios with a result of Na (1): Li (0.95): formamidine (1.27): guanidine (1.16): Cs (0.47): methylguanidine (0.72): methylamine (0.46) [25].
• Peroxisomal HAO differs from the other family members in that its actual physiological substrate is not known; it was first described as an L-amino acid oxidase, and recently was identified as an enzyme that converts creatol (hydroxycreatinine) to methylguanidine (a metabolite involved in a variety of uremic syndromes) [26].

Gene context of METHYLGUANIDINE

• Taken together, the present results demonstrate that methylguanidine exerts potent anti-inflammatory effects that could be, in part, related to an inhibition of the expression/activity of the iNOS and cyclooxygenase-2 and, another part, may be related to a reduction of TNF-alpha release [22].
• Diamine oxidase (histaminase) in chronic renal disease and its inhibition in vitro by methylguanidine [27].
• L-gulono-gamma-lactone oxidase is the enzyme responsible for the production of methylguanidine in the rat liver [28].
• For example, N-(2,5-dibromophenyl)-N'-(3-ethylphenyl)-N'- methylguanidine (27b, R2 = R5 = Br, R3 = C2H5) exhibited potency at both sigma receptors and NMDA receptor sites; 27b also showed high efficacy in vivo in a neonatal rat excitotoxicity model [29].
• N-methyl-D-aspartate receptor activation by guanidinosuccinate but not by methylguanidine: behavioural and electrophysiological evidence [30].

Analytical, diagnostic and therapeutic context of METHYLGUANIDINE

• RESULTS--Levels of methylguanidine in the poorly controlled group (1.31 +/- 0.08 microM) were significantly higher than those in both the well-controlled group (0.85 +/- 0.08 microM) and the control group (0.59 +/- 0.11 microM), respectively (P < 0.01) [7].
• Determination of methylguanidine in plasma and urine by high-performance liquid chromatography with fluorescence detection following postcolumn derivatization [31].
• Decreased serum antioxidant activity of hemodialysis patients demonstrated by methylguanidine synthesis and microsomal lipid peroxidation [32].
• The site of methylguanidine (MG) production in the kidney was investigated using animal models of renal disease and cultured renal epithelial cells [33].
• The chemical oxidative conversion of creatinine (Cr) into methylguanidine (MG) has been followed by 1H-NMR and HPLC [34].

References