oxalates and Thiamine-Deficiency

Topics: Ascorbic Acid; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Metabolism, Inborn Errors; Oxalates; Oxalic Acid; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Thiamine Deficiency; Vitamin B 6 Deficiency

Topics: Acute Kidney Injury; Alcohol Oxidoreductases; Animals; Asia, Southeastern; Calcium; Chemical Phenomena; Chemistry; Female; Glycols; Humans; Hydroxyproline; Infant; L-Lactate Dehydrogenase; Malabsorption Syndromes; Male; Methoxyflurane; Muscles; NAD; Oryza; Oxalates; Thiamine Deficiency; Urinary Calculi; Vitamin B 6 Deficiency

Topics: Animals; Carbon Isotopes; Glyoxylates; Keto Acids; Ketoglutaric Acids; Ligases; Mitochondria, Liver; Oxalates; Rats; Thiamine Deficiency; Valerates; Vitamin B 6 Deficiency

Evidence has been sought for minor degrees of thiamin and pyridoxine deficiency in patients undergoing surgery who have been infused with xylitol as a parenteral nutrient. Some metabolic changes which are associated with this practice have been studied; the findings are compared with those obtained in similar patients infused with glucose solutions. The thiamin status of all of the subjects was normal. Some of the patients showed slight biochemical evidence of pyridoxine deficiency, but there were no untoward effects of xylitol infusion. The concentration of oxalate in the blood and the excretion of oxalate in the urine did not exceed the normal range in any patient. The plasma and urine orthophosphate and urinary pyrophosphate levels decreased in association with the infusion of both xylitol and glucose. Plasma pyrophosphate and calcium levels, and the urinary calcium level, were essentially unaltered. A detailed quantitative study of the urinary organic acid excretion by means of gas chromatography/mass spectrometry showed that there was an abnormal glycolic aciduria and tetronic aciduria associated with xylitol infusion, but not with glucose infusion. There was no evidence of increased oxalate excretion in any patient by this method. The biochemical and clinical significance of these findings is discussed.

Topics: Adult; Calcium; Carboxylic Acids; Diphosphates; Female; Fructose; Glucose; Glycolates; Glyoxylates; Humans; Male; Middle Aged; Oxalates; Parenteral Nutrition; Phosphates; Postoperative Care; Sugar Acids; Thiamine Deficiency; Vitamin B 6 Deficiency; Xylitol

The chronic use of dichloroacetate (DCA) for diabetes mellitus or hyperlipoproteinemias has been compromised by neurologic and other forms of toxicity. DCA is metabolized to glyoxylate, which is converted to oxalate and, in the presence of adequate thiamine levels, to other metabolites. DCA stimulates the thiamine-dependent enzymes pyruvate dehydrogenase and alpha-ketoacid dehydrogenase. We postulated that the neurotoxicity from chronic DCA administration could result from depletion of body thiamine stores and abnormal metabolism of oxalate, a known neurotoxin. For 7 weeks, rats were fed ad lib. Purina chow and water or chow plus sodium DCA (50 mg/kg or 1.1 g/kg) in water. A portion of the DCA-treated animals also received intraperitoneal injections of 600 micrograms thiamine three times weekly or 600 micrograms thiamine daily by mouth. Thiamine status was assessed by determining red cell transketolase activity and, in a blinded manner, by recording the development of clinical signs known to be associated with thiamine deficiency. At the 50 mg/kg dose, chronic administration of DCA showed no clinical toxicity or effect on transketolase activity. At the 1.1 g/kg dose, however, DCA markedly increased the frequency and severity of toxicity and decreased transketolase activity 25%, compared to controls. Coadministration of thiamine substantially reduced evidence of thiamine deficiency and normalized transketolase activity. Inhibition of transketolase by DCA in vivo was not due to a direct action on the enzyme, however, since DCA, glyoxylate, or oxalate had no appreciable effects on transketolase activity in vitro. After 7 weeks, plasma DCA concentrations were similar in rats receiving DCA alone or DCA plus thiamine, while urinary oxalate was 86% above control in DCA-treated rats but only 28% above control in DCA plus thiamine-treated animals. No light microscopic changes were seen in peripheral nerve, lens, testis, or kidney morphology in either DCA-treated group, nor was there disruption of normal sperm production in the DCA-treated group. We conclude that stimulation by DCA of thiamine-requiring enzymes may lead to depletion of total body thiamine stores and to both a fall in transketolase activity and an increase in oxalate accumulation in vivo. DCA neurotoxicity may thus be due, at least in part, to thiamine deficiency and may be preventable with thiamine treatment.

Topics: Acetates; Animals; Body Weight; Dichloroacetic Acid; Erythrocytes; Male; Oxalates; Rats; Rats, Inbred Strains; Thiamine Deficiency; Time Factors; Transketolase

Male weanling rats were maintained on a thiamine-deficient diet for 4 weeks, and compared with ad libitum and pair-fed controls. Thiamine deficiency led to slow growth and finally a decrease in body weight. Liver and kidney weights of the deficient rats were low, but appropriate to the body weight. Thiamine deficiency also caused a significant decrease in erythrocyte transketolase levels. The decarboxylation of glyoxylate both via the glyoxylate oxidation cycle and alpha-ketoglutarate:glyoxylate (alpha-KG:GA) carboligase was significantly lower in the liver and kidney mitochondria, leading to accumulation of glyoxylate in the tissues and its excretion in the urine. Part of the accumulated glyoxylate is converted to oxalate, causing hyperoxaluria.

Topics: Aldehyde-Ketone Transferases; Animals; Glyoxylates; Kidney; Male; Mitochondria; Mitochondria, Liver; Oxalates; Oxidation-Reduction; Oxo-Acid-Lyases; Rats; Rats, Inbred Strains; Thiamine Deficiency

Dietary deficiency of thiamine or pyridoxine has been shown to produce hyperoxaluria and renal stone formation in man and experimental animals. To determine the possible contribution of exogenous glyoxylate and oxalate, the intestinal transport of [14C] - oxalate and [14C] - glyoxylate was measured in vitamin B1 and B6 deficient rats and their respective pair-fed controls. Results indicate that glyoxylate and oxalate are passively diffused from lumen to lamina propria in thiamine deficient and their pair-fed controls with no significant change in the rate of uptake of both the substrates. However B6 deficient rats showed a significant enhancement in the rate of oxalate uptake due to development of a new biphasic transport system. The rate of glyoxylate uptake by simple passive diffusion remained unaltered in pyridoxine deficiency.

Topics: Animals; Glyoxylates; In Vitro Techniques; Intestinal Absorption; Intestinal Mucosa; Kinetics; Male; Oxalates; Oxalic Acid; Pyridoxine; Rats; Rats, Inbred Strains; Thiamine; Thiamine Deficiency; Vitamin B 6 Deficiency

Glucose, fructose, sorbitol and xylitol were assessed as precursors of oxalate in normal rats and rats deficient in thiamin or vitamin B-6. Urinary excretions of oxalate, glyoxylate and glycine were increased significantly in vitamin B-6 deficient rats infused with xylitol when compared with all other groups. Using [U-14C]xylitol, oxalate was shown to be derived directly from this polyalcohol in vitamin B-6 deficient rats. These results suggest that vitamin B-6 deficiency may be a factor contributing to oxalate crystal deposition seen in some patients infused with xylitol.

Topics: Animals; Infusions, Parenteral; Male; Oxalates; Pyridoxine; Rats; Thiamine; Thiamine Deficiency; Vitamin B 6 Deficiency; Xylitol

Oxalate levels in the plasma and urine fractions of fasted normal, oxythiamin treated (20 mg/kg) and 4-deoxypyridoxine treated (300 mg/kg) rabbits were determined following infusion with either xylitol or glucose at a dose of 2 g/kg body weight. Biochemical determinations showed that transient thiamin or pyridoxine deficient states had been induced in the antivitamin treated rabbits. In the first 24 hour following infusion with either carbohydrate, urinary oxalate levels remained within the normal range for all groups. Oxythiamin hastened the appearance of the transient, elevation in plasma oxalate concentrations seen in rabbits after infusion with glucose. After xylitol infusion, the elevation of plasma oxalate was not significnatly above normal. 4-Deoxypyridoxine enhanced peak plasma oxalate levels above those of controls for both sugars. Glucose, at an equivalent dose to xylitol, resulted in higher plasma oxalate levels than xylitol for all groups. Infusions of [U-14C]xylitol and [U-14C]glucose solutions into 4-deoxypyridoxine treated rabbits demonstrated a conversion of the administered radioactive carbon into 14C oxalate of 0.01% with a high dilution of the specific activity. The results suggest that oxalate production from xylitol is negligible; any toxicity related to xylitol administration is not a consequence of oxalate production.

Topics: Animals; Antimetabolites; Glucose; Male; Oxalates; Oxythiamine; Pyridoxine; Rabbits; Thiamine Deficiency; Thiazoles; Vitamin B 6 Deficiency; Xylitol

Oxalate metabolism was assessed in normal rats and rats deficient in vitamins B-1 and B-6 during intravenous infusions of solutions containing glucose, fructose, sorbitol or xylitol. Urinary excretions of oxalate, glyoxylate and glycine were considerably increased in vitamin B-6 deficient rats infused with xylitol. Significant amounts of 14C-oxalate were excreted only in vitamin B-6 deficient rats infused with U 14C-xylitol. Correction of vitamin B-6 deficiency resulted in a return to normal of urinary oxalate excretion and percentage of U 14C-xylitol excreted as 14C-oxalate. The results suggest that xylitol metabolism produces an increased activity in pathways leading to oxalate formation in vitamin B-6 deficient rats.

Topics: Animals; Creatinine; Fructose; Glucose; Glycine; Glyoxylates; Hexoses; Humans; Infusions, Parenteral; Male; Oxalates; Rats; Sorbitol; Sugar Alcohols; Thiamine Deficiency; Vitamin B 6 Deficiency; Xylitol

Type I hyperoxaluria results from reduced activity of alpha-ketoglutarate: glyoxylate carboligase, which is necessary for the synergistic decarboxylation of glyoxylate and alpha-ketoglutarate to alpha-hydroxy-beta-keto-adipate. Since thiamine pyrophosphate is a cofactor in the reaction, thiamine deficiency might be expected to result in tissue oxalosis. However, there was no significant increase in the incidence of renal oxalosis in 15 patients with Wernicke's encephalopathy at necropsy compared with controls. It is possible that hyperoxaluria was present in these thiamine-deficient patients but at a urine concentration below that necessary for calcium oxalate deposition. It is also possible that the severity of the thiamine deficit required for hyperoxaluria exceeds that for the neuronal and cardiac manifestations.

Topics: Acute Kidney Injury; Adipates; Adult; Carboxy-Lyases; Diphosphates; Glyoxylates; Humans; Ketoglutaric Acids; Kidney Diseases; Metabolic Diseases; Middle Aged; Oxalates; Thiamine; Thiamine Deficiency; Wernicke Encephalopathy

Topics: Alanine; Animals; Carbon Isotopes; Ethanolamines; Female; Glycine; Glycolates; Glycols; Glyoxylates; Kidney; Liver; Methionine; Oxalates; Oxidation-Reduction; Perfusion; Pyridoxine; Rats; Serine; Thiamine; Thiamine Deficiency; Time Factors; Vitamin B 6 Deficiency

Topics: Animal Nutritional Physiological Phenomena; Animals; Calcium; Crystallization; Food Deprivation; Glycine; Glycols; Glyoxylates; Kidney; Kidney Calculi; Male; Myocardium; Oxalates; Rats; Thiamine Deficiency; Time Factors; Vitamin B 6 Deficiency

Topics: Animals; Formates; Glyoxylates; Male; Oxalates; Thiamine Deficiency; Urinary Calculi

Topics: Animals; Autoradiography; Chemical Phenomena; Chemistry; Chromatography, Ion Exchange; Enzymes; Erythrocytes; Female; Glucose; Glycolates; Humans; Infant, Newborn; Ketoglutaric Acids; Leukocytes; Male; Oxalates; Oxidation-Reduction; Pyruvates; Thiamine; Thiamine Deficiency; Transferases