Biosynthesis of Methylguanidine in Isolated Rat Hepatocytes and in vivo

Nagase, Sohji; Aoyagi, Kazumasa; Narita, Mitsuharu; Tojo, Shizuo

doi:10.1159/000183523

Cited by 47 publications

(41 citation statements)

References 11 publications

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“…Based on the reported Crn levels in rat organs (Figure 4) (7), and the reported MG levels in rat organs induced by Crn injection (21,24) and autoradiogram 14 C-Crn (20), sites and organs where Crn scavenges •OH in mammals was presumed ( Figure 5). One-way flow of Crn from muscles and the brain, where Crn is synthesized and its concentration remains at a high level, into blood vessels was observed.…”

Section: Prediction Of Sites Where Crn Scavenges •Oh In Mammalsmentioning

confidence: 99%

Daily hydroxyl radical scavenging capacity of mammals

Ienaga

Park

Yokozawa

2014

DD&T

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Section: Prediction Of Sites Where Crn Scavenges •Oh In Mammalsmentioning

confidence: 99%

Daily hydroxyl radical scavenging capacity of mammals

Ienaga

Park

Yokozawa

2014

DD&T

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“…[1][2][3] Studies revealed that the liver and the kidneys oxidize CTN into creatol, which is converted into MG. [4][5][6][7] Oxidation of CTN with active oxygen (e.g., hydrogen peroxide) was proven to generate MG, whereas scavengers of active oxygen (e.g., glutathione, sorbitol) considerably reduced MG synthesis. 8 MG is expelled mainly from the kidney and is considered as not only a neurotoxin [9][10][11] but also a critical uremic toxin.…”

Section: Introductionmentioning

confidence: 99%

Methylguanidine cytotoxicity on HK-2 cells and protective effect of antioxidants against MG-induced apoptosis in renal proximal tubular cellsin vitro

et al. 2010

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The present study was designed to explore the toxic effect of MG on renal proximal tubular cells as well as the protective effect of antioxidants PGE1 and probucol against MG-induced apoptosis in renal proximal tubular cells. HK-2 cells were used as the subject. The cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. N-Acetyl-3-D-glucosaminidase (NAG) activity, malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity were determined. Cell apoptosis was determined by flow cytometry (light scatter and propidium iodide/annexin V-FTC fluorescence) and by nuclear staining with Hoechst 33258. Cells were exposed to MG (0.25, 0.5, or 1 mmol/L), MG (0.5 mmol/L) + PGE1 (2 μg/L), and MG (0.5 mmol/L) + probucol (20 μmol/L) respectively for 24 h. MG induced a significant dose-dependent loss of cell viability. Both PGE1 and probucol improved the viability of MG-treated HK-2 cells. Cells showed apoptotic morphology (deepened stain, karyopyknosis, and apoptotic body) when exposed to 0.5 mmol/L MG for 24 h, and the apoptosis ratio was increased compared with the control. The presence of PGE1 or probucol significantly lowered the apoptotic ratio. Moreover, PGE1 or probucol notably decreased the MDA content and increased the SOD activity compared with when the cells were treated with MG only. The results of the present study clearly demonstrate that MG could promote apoptosis of renal proximal tubular cells in vitro. Both PGE1 and probucol could protect renal proximal tubular cells from MG-induced apoptosis.

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“…It is also conceivable that for unknown physiological reasons the rabbit or rabbit kidney needs high tissular levels of GAA, CT and CTN. The production of MG from CTN has been demonstrated in rat hepatocytes (Nagase, Aoyagi, Narita & Tojo, 1985;Nagase, Aoyagi, Sakamoto, Ishikawa & Narita, 1992). Since the plasma (< 0-020 tM; n = 11 rabbits) and renal concentrations of MG were very low in rabbit compared with rat (Levillain et al 1995), we hypothesized that the intensity of this metabolic pathway might be weaker in the rabbit.…”

Section: Discussionmentioning

confidence: 98%

Renal handling of guanidino compounds in rat and rabbit.

Levillain

Marescau

Deyn

1997

The Journal of Physiology

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1. Guanidino compounds (GCs) have been quantified in different mammalian tissues such as brain, liver, muscle and kidney. The high anatomical heterogeneity of the kidney suggests that GCs could be unevenly distributed along the corticopapillary axis of the kidney in different species. 2. This study was designed to quantify twelve GCs in the different zones of rat and rabbit kidney. The kidneys were sliced and pieces of seven definite zones were weighed and homogenized for further GC extraction. GCs were determined by liquid chromatography. 3. The results indicate that: (1) GCs were unevenly distributed along rat and rabbit kidney; (2) qualitative and quantitative studies proved that each GC shows a particular distribution pattern along the corticopapillary axis for a given species; (3) in rats, alpha‐keto‐delta‐guanidinovaleric acid, guanidinosuccinic acid, creatinine (CTN), methylguanidine and to a lesser extent gamma‐guanidinobutyric acid increased steeply along the inner medulla in parallel to urea, whereas in rabbits, most of the GCs reached a plateau in the inner medulla and remained constant at this level; (4) gamma‐guanidinobutyric acid was specifically found in the rat kidney; (5) argininic acid was higher in rabbit compared with rat kidney; (6) significantly higher levels of homoarginine were found in all zones of the rat kidney compared with the rabbit kidney. 4. The results suggest that: (1) GCs are mostly localized within the nephron segments; (2) an accumulation of GCs in the inner medulla might be explained either by a recycling process or by an intracellular storage as has been reported for urea, amino acids and organic osmolytes; (3) some GCs might be synthesized in nephron segments as reported for arginine (Arg) and guanidinoacetic acid (GAA); (4) several metabolic pathways of the GCs seemed to differ between rat and rabbit; (5) except for creatine, CTN, Arg and GAA, it seems unlikely that GCs might significantly increase the intracellular osmolality.

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Biosynthesis of Methylguanidine in Isolated Rat Hepatocytes and in vivo

Cited by 47 publications

References 11 publications

Daily hydroxyl radical scavenging capacity of mammals

Daily hydroxyl radical scavenging capacity of mammals

Methylguanidine cytotoxicity on HK-2 cells and protective effect of antioxidants against MG-induced apoptosis in renal proximal tubular cellsin vitro

Renal handling of guanidino compounds in rat and rabbit.

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