guanidinosuccinic-acid and gamma-guanidinobutyric-acid

The use of anisoin as pre-chromatographic reagent for LC analysis of guanidino compounds is proposed. The reagent reacts (5 min at 100 degrees C) with guanidino function and the resulting adducts can be chromatographed under reversed-phase conditions. A fluorescence detector (lambda(ex)=325 nm; lambda(em)=435 nm) was used to detect guanidino adducts. The derivatization and chromatographic conditions were optimised by a series of experiments. Application to the determination of arginine and creatine in pharmaceuticals and arginine, guanidine, methylguanidine, guanidinosuccinic acid, beta-guanidinopropionic acid, gamma-guanidinobutyric acid, guanidinoacetic acid and homoarginine in human urine is described. Quantitation limits ranged from 6 to 30 fmol, except for creatine (510 fmol).

Topics: Benzoin; Chromatography, Liquid; Guanidines; Pharmaceutical Preparations; Propionates; Succinates

Arginine (Arg) produced from citrulline originates mostly from kidneys. Arg is involved in guanidino compound biosynthesis, which requires interorgan co-operation. In renal insufficiency, citrulline accumulates in the plasma in proportion to renal damage. Thus, disturbances in Arg and guanidino compound metabolism are expected in several tissues. An original use of the model of nephrectomy based on ligating branches of the renal artery allowed us to investigate Arg and guanidino compound metabolism simultaneously in injured (left) and healthy (right) kidneys. The left kidney of adult rats was subjected to 72% nephrectomy. Non-operated, sham-operated and nephrectomized rats were studied for a period of 21 days. Constant renal growth was observed only in the healthy kidneys. Guanidino compound levels were modified transiently during the first 48 h. The metabolism and/or tissue content of several guanidino compounds were disturbed throughout the experimental period. Arg synthesis was greatly reduced in the injured kidney, while it increased in the healthy kidney. The renal production of guanidinoacetic acid decreased in the injured kidney and its urinary excretion was reduced. The experimentally proven toxins alpha-keto-delta-guanidinovaleric acid and guanidinosuccinic acid (GSA) accumulated only in the injured kidney. The urinary excretion of GSA and methylguanidine increased in nephrectomized rats. When the injured kidney grew again, the level of some guanidino compounds tended to normalize. Nephrectomy affected the guanidino compound levels and metabolism in muscles and liver. In conclusion, the specific accumulation of toxic guanidino compounds in the injured kidney reflects disturbances in renal metabolism and function. The healthy kidney compensates for the injured kidney's loss of metabolic functions (e.g. Arg: production). This model is excellent for investigating renal metabolism when a disease destroys a limited area in one kidney, as is observed in patients.

Topics: Acute Kidney Injury; Animals; Arginine; Creatine; Creatinine; Glycine; Guanidines; Homoarginine; Kidney; Kidney Failure, Chronic; Male; Methylguanidine; Muscle, Skeletal; Nephrectomy; Propionates; Rats; Rats, Sprague-Dawley; Succinates; Time Factors; Urea; Uremia

The long-term adverse consequences of early renal mass reduction in mice have not yet been investigated. The effects of partial surgical nephrectomy (NX) in 2-month-old mice on some biological parameters, on histopathologic and morphometric features of the kidney, and on urea and guanidino compound (GC) levels in plasma, urine, and brain were examined at 10 days, and 1, 2, 4, and 12 months postsurgery. Body weight, urinary volume, and plasma urea were most affected at 10 days and 12 months post-NX. NX-induced changes in the remaining renal tissue (including hypertrophy, glomerular mesangial expansion, and presence of protein casts) increased with age. As in human renal insufficiency, NX mice showed significantly higher plasma guanidinosuccinic acid (GSA) and creatinine (CTN) levels at all studied periods. The same tendency could be seen for most other plasma GCs examined, except for arginine (Arg), guanidinoacetic acid (GAA), and homoarginine (HA). As seen in human pathobiochemistry, the latter 2 compounds tended to be lower in NX mice in our follow-up study. Remarkably, and also similar to humans, NX mice excreted less GAA and more GSA than controls during the entire follow-up study. During the follow-up, excretion levels of GAA were unchanged in NX and sham-operated mice. In brain, GAA and gamma-guanidinobutyric acid (GBA) levels were always higher in NX mice with a tendency to respectively increase or decrease over time in NX as well as sham-operated mice. Although urea and GC metabolism were influenced by time post-NX and aging, the model was confirmed to display a mild stable chronic impairment of renal function. Histopathologic and morphometric changes of the kidney increased with age.

Topics: Aging; Animals; Arginine; Brain Chemistry; Creatinine; Glycine; Guanidines; Homoarginine; Humans; Hypertrophy; Kidney; Male; Mice; Mice, Inbred C57BL; Nephrectomy; Succinates; Urea

Renal failure is characterized by the retention of nitrogenous metabolites such as urea, creatinine (CTN) and other guanidino compounds (GCs), uric acid, and hippuric acid, which could be related to the clinical syndrome associated with renal insufficiency. A model of renal failure has been developed in male C57BL x Swiss-Webster mice using nephrectomy (NX) and/or arterial ligation. A sham group (group A) and two nephrectomized groups, group B (one kidney removed) and group C (one kidney removed and ligation of the contralateral anterior artery branch), were studied. Ten days postsurgery, morphological and functional indices of renal failure were investigated. Nephrectomized mice manifested features of renal failure like polyuria and wasting. CTN clearance (CTN[Cl]) decreased by +/-26% in group B and +/-33% in group C as compared with the control values. Marked increases in the plasma concentration of guanidinosuccinic acid ([GSA] fourfold) and guanidine ([G] twofold) were observed in the experimental animals. CTN and alpha-keto-delta-guanidinovaleric acid (alpha-keto-delta-GVA) reached levels of, respectively, 1.5-fold and twofold those of controls. Urinary GSA excretion increased and guanidinoacetic acid (GAA) excretion decreased about twofold in group C. GSA increases (2.6-fold) were also observed in the brain in group C, in addition to a significant increase of G (2.5-fold) and gamma-guanidinobutyric acid ([GBA] 1.5-fold). Finally, the extent of NX was found to be 45.2% in group B and 71.4% in group C. Light microscopy revealed an expansion and increase in cellularity of the mesangium of the glomeruli, particularly in group C. A significant correlation (r = .574, P < .0001) was found between CTN(Cl) and the degree of NX as calculated from the remaining functional area. These data suggest that the model can be used as a tool for further pathophysiological and/or behavioral investigations of renal failure.

Topics: Animals; Arginine; Brain; Creatinine; Glycine; Guanidine; Guanidines; Ligation; Male; Mice; Mice, Inbred C57BL; Nephrectomy; Renal Artery; Renal Insufficiency; Succinates

Arginine levels diminished markedly in the plasma during starvation, suggesting that plasma arginine level principally depends on food intake. Organ arginine levels were relatively stable except for an extraordinary increase in the pancreas at 96 h. Guanidinoacetic acid decreased dramatically in all organs within 24 h and low level were maintained thereafter, except for the brain (and plasma). Creatinine output increased after 24h of starvation. The increased creatinine output recovered to the control level after 48 h. A small but significant amount of guanidinosuccinic acid was detected in the normal liver and decreased transitorily after 24 h and increased after 48 h starvation, corresponded with an increased output in the 24 h urine excretion. Otherwise this decrease may be related to the transitory decrease in arginine level in the liver over the same time course. Methylguanidine in the muscle and gamma-guanidinobutyric acid in the liver decreased gradually during starvation. These results suggest that guanidino compounds levels in mouse organs are principally dependent on exogenous nitrogen.

Topics: Animals; Arginine; Creatinine; Glycine; Guanidines; Male; Methylguanidine; Mice; Starvation; Succinates

Topics: Amino Acid Metabolism, Inborn Errors; Arginine; Chromatography, Liquid; Chromatography, Thin Layer; Female; Gas Chromatography-Mass Spectrometry; Glycine; Guanidines; Humans; Hyperargininemia; Succinates