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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The toxic effects of metabolites that are known to accumulate in renal failure are described and the role that they may play in causing uremic symptoms is considered. The opinion of the Authors is that all they are likely to take a lesser or greater part in uremic intoxication. Methylguanidine seems to be very important in this context while for some others (like amines) nothing can be stated for studies on their chronic toxicity are lacking. The hypothesis is also considered of the accumulation of unidentified toxic metabolites with a middle molecular weight. It is stated, as to this problem, that the clinical evidence apparently supporting univocally their existence, is instead also consistent with the hypothesis of toxins (like methylguanidine) having a preferential distribution in the intracellular fluid compartment.
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PMID:Uremic intoxication. 109 53

1. Methylguanidine administered orally to normal volunteers was almost completely recovered in the urine, indicating that it is absorbed in the gastrointestinal tract and is not converted into other compounds. In normal persons at least, its urinary output therefore corresponds to its metabolic production rate plus the amount ingested. 2. In normal persons, diets based on foods not containing methylguanidine (e.g. vegetarian, protein-free and milk-egg) caused a fall in the urinary output of methylguanidine as compared with the output of the same subjects on a free diet. Conversely, higher amounts of methylguanidine were excreted on a diet rich in broth and in boiled beef, which contain large amounts of methylguanidine formed from the oxidation of creatinine, caused by boiling. 3. Oral administration of creatinine to normal volunteers induced an immediate and marked increase in urinary excretion of methylguanidine, and the ingestion of [methyl-14-C]creatinine by uraemic patients was followed by the urinary excretion of labelled methylguanidine. These findings indicate that creatinine is partly converted into methylguanidine in both normal and uraemic subjects and accounts for the high metabolic production of methylguanidine in patients with renal failure, in whom the body pool of creatinine is high. 4. Creatinine, incubated at 38 degrees C for 24 h in Krebs bicarbonate solution (pH 7-38) through which was bubbled oxygen with 15% carbon dioxide, was partially oxidized to methylguanidine. This raises the possibility that even in vivo such a conversion may occur "non-enzymatically".
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PMID:Factors affecting the metabolic production of methylguanidine. 112 27

1. Methylguanidine is a suspected uraemic toxin that accumulates in renal failure. 2. We measured methylguanidine in the plasma of dogs with acute ischaemic-induced renal failure and in the plasma and urine of dogs with spontaneous chronic renal insufficiency, using a highly sensitive method involving solid-phase extraction followed by h.p.l.c. with post-column fluorescence detection. 3. Constriction of the remaining renal artery of four uninephrectomized dogs for 90 min resulted in a significant (P less than 0.01) increase in plasma creatinine concentration after 24 h (from 113 +/- 3 to 303 +/- 50 mumol/l; mean +/- SEM). Over the next 14 days, plasma creatinine fell towards baseline concentrations. Plasma methylguanidine also increased significantly (P less than 0.05) 24 h after renal occlusion (from 0.16 +/- 0.04 to 0.86 +/- 0.32 mumol/l) and showed a similar pattern to the plasma creatinine concentration. 4. In a further four dogs, administration of mannitol (2 g/kg) at the time of reperfusion significantly attenuated these responses. 5. Dogs with chronic renal failure demonstrated increased plasma concentrations and urinary excretion of methylguanidine, and the levels appeared to be related to the severity of renal insufficiency. Thus, the dogs with the highest plasma creatinine concentrations and lowest creatinine clearances had the highest plasma methylguanidine concentrations. The clearance of methylguanidine exceeded that of creatinine, indicating that the toxin undergoes renal tubular secretion.
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PMID:Production of methylguanidine in dogs with acute and chronic renal failure. 260 68

Methylguanidine (MG) was intraperitoneally administered to both normal rats and those given adenine, and MG levels in the serum, liver, kidney, muscle, brain and urine were compared. The accumulation of MG in the body increased with the progression of renal failure, whereas the rate of urinary excretion of MG in rats given adenine for 30 days was lower than the corresponding values in rats given adenine for 10 and 20 days. The velocity of MG elimination from serum and tissues became lower as the period of adenine administration lengthened. In particular, the rate of MG elimination from muscle was markedly low in comparison with that from the serum, liver, kidney or brain, and a high concentration of MG was still present 24 h after MG loading. In addition, the amount of MG obtained by subtracting the total amounts detected in the serum, liver, kidney, muscle, brain and urine from the dose decreased gradually as the period of adenine administration lengthened. The MG-scavenging effect is diminished according to the progress of renal failure.
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PMID:Variations in the distribution of methylguanidine with the progression of renal failure after methylguanidine loading. 277 Sep 51

Methylguanidine (MG), guanidinosuccinic acid (GSA) and creatinine (Cr), which accumulate in the body in parallel with the progress of renal failure after adenine administration, were given separately to rats in order to compare their toxicities. Food containing adenine was given to rats for 24 days to induce renal failure, and then each of the test substances was administered intraperitoneally from the following day, the survival rates of the rats being subsequently determined. Administration of MG at varying doses produced a dose-dependent decrease in the survival rate, whereas the survival curves obtained for rats given GSA or Cr indicated weak toxicity. The levels of MG, GSA or Cr accumulated in the body were extraordinarily high in surviving rats after 14 days of administration of each respective compound. The toxic effects are discussed on the basis of these results.
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PMID:Comparison of toxic effects of methylguanidine, guanidinosuccinic acid and creatinine in rats with adenine-induced chronic renal failure. 291 50

Aminoguanidine, NG-monomethyl-L-arginine (L-NMMA), NGNGdimethyl-L-arginine (asymmetric dimethylarginine; ADMA), creatinine, guanidinosuccinic acid, guanidinoproprionic acid and methylguanidine were added to cultures of activated murine macrophages. Only aminoguanidine, ADMA, L-NMMA and methylguanidine inhibited nitrite production in a dose-dependent manner. In the presence of 100 microM arginine, nitrite production was inhibited by 31.8 +/- 7.1% by ADMA (100 microM; P < 0.01) but the same dose of methylguanidine was without effect. A higher dose of methylguanidine (1000 microM) inhibited nitrite production by 47.6 +/- 5.6% (P < 0.001). The effects of these compounds were also tested on relaxation of human saphenous veins. L-NMMA and ADMA inhibited endothelium-dependent relaxations (EC50 = 4.7 +/- 1.1 microM and 17.9 +/- 4.9 microM, respectively); methylguanidine caused endothelium-independent contractions and reversed the relaxations to bradykinin and sodium nitroprusside (EC50 > 100 microM); aminoguanidine was without effect. The results of this study suggest that of the guanidino compounds which accumulate in renal failure, only ADMA is a potent inhibitor of nitric oxide (NO) synthesis. Methylguanidine is a weak inhibitor of nitric oxide synthesis, whereas the closely related compound aminoguanidine appears to inhibit selectively the inducible isoform of nitric oxide synthase and has no effect on constitutive NO synthase in human veins.
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PMID:Effects of guanidino and uremic compounds on nitric oxide pathways. 751 29

Methylguanidine, guanidinoacetic acid and guanidinosuccinic acid are endogenous substances in body tissues. Extremely high levels of these substances are known to be related to the pathogenesis of epilepsy and renal failure such as uremia. In this study it was demonstrated that methylguanidine, guanidinoacetic acid and guanidinosuccinic acid, and arginine generate hydroxyl radicals in aqueous solution. These findings suggest that a high level of guanidino compounds accumulating near or within cells such as neurons (in an epileptogenic focus) or nephrons (in uremic patients) may cause free radical damage leading to these clinical disorders. Arginine may have a similar role in the pathogenesis of hyperarginemia.
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PMID:Guanidino compounds generate reactive oxygen species. 888 79

Methylguanidine (MG) is widely recognized as a strong uremic toxin. The hydroxyl radical (*OH) specifically plays an important role in the pathway of MG production from creatinine (Cr). In this study, we investigated whether oral administration of (-)-epigallocatechin 3-O-gallate (EGCg) suppresses MG production in rats with chronic renal failure after intraperitoneal Cr injection. MG production from Cr was significantly increased in rats with adenine-induced renal failure, which was more vulnerable to oxidative stress, compared with that in normal rats. However, oral administration of EGCg 30 min before and after Cr injection effectively inhibited MG production. Our findings suggest that EGCg, an excellent antioxidant from green tea, exerts protective activity in rats with chronic renal failure, resulting in suppression of Cr oxidation influenced by *OH.
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PMID:Activity of (-)-epigallocatechin 3-O-gallate against oxidative stress in rats with adenine-induced renal failure. 1505 59