Malondialdehyde derivatives in urine.
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Animals↗
Biomedical subjects
H H Draper
Publications and source records attributed to H H Draper.
Identification of N-epsilon-(2-propenal)lysine as a major urinary metabolite of malondialdehyde.
N-epsilon-(2-propenal)lysine (epsilon-PL) was identified as one of two major metabolites of malondialdehyde (MDA) excreted in rat and human urine. This compound is derived mainly but not exclusively from the diet, where it arises from a reaction between free MDA generated in the oxidative decomposition of polyunsaturated fatty acids and the epsilon-amino of the lysine residues of food proteins. It is released during protein digestion and represents the main form in which MDA is absorbed. It is excreted partially in unchanged form and partially as the acetylated derivative N-alpha-acetyl-N-epsilon-(2-propenal)lysine. Its administration to rats did not result in an increase in the excretion of free MDA in the urine. The findings that MDA in foods is absorbed mainly as epsilon-PL, and that this compound is not metabolized to free MDA in vivo, mitigate concern over the possible mutagenicity and carcinogenicity of MDA in the diet.
Animals↗
Malondialdehyde excretion by subjects consuming cod liver oil vs a concentrate of n-3 fatty acids.
Urinary malondialdehyde (MDA), an indicator of lipid peroxidation in the diet and in the tissues, was determined in human adults consuming a supplement of n-3 fatty acids derived from a pharmaceutical grade of cod liver oil (CLO) without added antioxidants vs a concentrate of n-3 acids containing dodecyl gallate and vitamin E. MDA excretion increased immediately in the subjects consuming CLO but remained unchanged in those ingesting the concentrate for 50 days. The increase in the subjects taking CLO was attributable to MDA in the oil. The results indicate that consuming unstabilized fish oils as a source of n-3 fatty acids may entail exposure to potentially toxic products of lipid peroxidation.
Adult↗
Identification of N-epsilon-(2-propenal)lysine as the main form of malondialdehyde in food digesta.
The form(s) in which malondialdehyde (MDA), a mutagenic product of the oxidative decomposition of polyunsaturated fatty acids (PUFA), occurs in foods was investigated. Several foods of animal origin (ground beef, smoked fish, chicken, sausages) were digested in vitro using pepsin and porcine intestinal fluid and the occurrence of MDA derivatives in the digesta was investigated by thin-layer, column and high-performance liquid chromatography. The predominant form of MDA was shown to be identical to synthetic N-epsilon-propenal lysine. This compound is apparently formed by a reaction between free MDA generated as a product of the oxidative rancidity of PUFA in foods and the free epsilon-amino groups of proteins, from which it is released in the course of digestion. It has been shown to be excreted in rat and human urine partially in the unchanged form and partially as the N-alpha-acetyl derivative. The results of this study serve to mitigate concern over the possible carcinogenicity of MDA in the diet, since less than 10% of the MDA in several foods containing highly unsaturated fatty acids was found in the free form.
Animals↗
Nutrients as nutrients and nutrients as prophylactic drugs.
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Humans↗
Vitamin D metabolism in the hooded seal (Cystophora cristata).
Fish-eating mammals, such as seals, appear to ingest levels of vitamin D that are toxic to most mammals. To determine how seals cope with high vitamin D intakes, the metabolism of tritiated cholecalciferol ([3H]D3) was investigated in hooded seal (Cystophora cristata) pups during their postweaning fast and pups and adults consuming herring alone or supplemented with 400,000 iu D3 daily. [3H]D3 was metabolized to 25-[3H]OHD3 and 24,25-[3H](OH)2D3. 1,25-[3H](OH)2D3 was not detected, but plasma levels of 1,25-(OH)2D were similar to those in other mammals and were not affected by vitamin D intake. Plasma vitamin D, 25-OHD and 24,25-(OH)2D increased with vitamin D intake, but 25-OHD did not increase to the extent seen in other mammals. The supplemented seals showed no evidence of toxicity. Levels of 24,25-(OH)2D were higher in the unsupplemented seals (4 to 33 ng/mL) than reported in other mammals with similar 25-OHD levels and did not decrease with 25-OHD. High levels of 24,25-(OH)2D relative to 25-OHD have also been found in hooded seals in the wild. The half-lives of vitamin D, 25-OHD and 24,25-(OH)2D were shorter than those reported for most other mammals. Increased conversion of 25-OHD to 24,25-(OH)2D and a high capacity for vitamin D storage in their large blubber mass appeared to be factors in the resistance of seals to vitamin D toxicity.
Animals↗
Identification of N-(2-propenal) serine as a urinary metabolite of malondialdehyde.
N-2-(Propenal) serine (S-MDA) was synthesized by reacting serine with malondialdehyde (MDA) and was shown to be a 1:1 adduct of the starting materials. The synthetic compound was found to be identical to a metabolite of MDA excreted in rat and human urine. The identity of the metabolite was confirmed by isolation and hydrolysis to yield equimolar quantities of serine and MDA. The presence of S-MDA in urine constitutes direct evidence for oxidative decomposition of phospholipids by lipid peroxidation in vivo.
Animals↗
Response of urinary malondialdehyde to factors that stimulate lipid peroxidation in vivo.
Malondialdehyde (MDA) derivatives occur as normal constituents of rat and human urine. In a previous study, it was found that MDA excretion in rats is responsive to MDA intake and to certain factors that increase lipid peroxidation in vivo: vitamin E deficiency, iron administration and a high concentration of cod liver oil (CLO) fatty acids in the tissues. In the present study, the effect on MDA excretion of several additional dietary and endogenous factors was evaluated. The composition of dietary fatty acids had a major influence on MDA excretion in fed animals, being highest for animals fed n-3 fatty acids (20:5 and 22:6) from CLO, intermediate for those fed n-6 (18:2) acids from corn oil (CO) and lowest for those fed saturated acids from hydrogenated coconut oil (HCO). Diet was the main source of urinary MDA in all groups. Fasting produced a marked increase in urinary MDA, which tended to be higher in rats previously fed CLO. Fasting MDA excretion was not affected by the level of CO in the diet (5, 10 or 15%), indicating that feeding n-6 acids does not increase lipid peroxidation in vivo. Adrenocorticotropic hormone and epinephrine administration increased urinary MDA, further indicating that lipolysis either releases fatty acid peroxides from the tissues or increases the susceptibility of mobilized fatty acids to peroxidation. A decrease in fasting MDA excretion was observed in rats previously fed a high level of antioxidants (vitamin E + BHT + vitamin C) vs a normal level of vitamin E. MDA excretion increased following adriamycin and CCl4 administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenocorticotropic Hormone↗
Micronutrients and cancer prevention: are the RDAs adequate?
The involvement of certain micronutrients (vitamin C, vitamin E, beta-carotene, selenium) in the antioxidant defense system against free radical cell damage, and of vitamin A in the differentiation of epithelial cells, has raised the question whether intakes of these nutrients in excess of their recommended daily allowances should be recommended to the general public for cancer prevention. The considerations surrounding this question are discussed, and it is concluded that such measures are unjustified by present epidemiological and experimental evidence. Any such action should await the outcome of ongoing intervention trials.
Ascorbic Acid↗
The vitamin D status of East Indian Punjabi immigrants to Canada.
1. Serum 25-hydroxyvitamin D (25-OHD), calcium and alkaline phosphatase (EC 3.1.3.1) levels and vitamin D intakes (from 3 d weighed dietary records) were determined in a cohort of fifty-nine male East Indian Punjabi immigrants (37.7 (SD 10.5) years) and fifty-four females (33.3 (SD 7.4) years). 2. Females had somewhat lower mean serum 25-OHD levels (12.3 (SD 5.0) v. 14.2 (SD 5.1) ng/ml, P less than 0.05) and serum Ca levels (88 (SD 8) v. 91 (SD 6) mg/l) than males (P less than 0.05) whereas serum alkaline phosphatase values (males 167 (SD 63), females 169 (SD 43) IU/l) and dietary vitamin D intakes (males 3.5 (SD 1.8), females 3.3 (SD 2.0) micrograms/d) were similar. 3. 22% of the females and 12% of the males had serum 25-OHD levels below 9.0 ng/ml but none had serum 25-OHD levels within the range associated with clinically overt disease. 4. In the males, serum 25-OHD levels were negatively correlated with dietary fibre intakes (g/d; r -0.29; P less than 0.05). 5. Multiple-regression analysis indicated that log serum 25-OHD levels were not related to dietary vitamin D intakes. Instead they were associated with sex and dietary fibre intakes (g/MJ) (F 3.71; P = 0.03). These two variables explained 8% of the variance.
Adult↗
The metabolism of malondialdehyde.
Interest in malondialdehyde (MDA) metabolism stems from its formation as a product of lipid peroxidation in the diet and in the tissues; its reactivity with functional groups of nucleic acid bases, proteins and phospholipids; its mutagenicity in bacteria, and its reported skin and liver carcinogenicity in animals. Administration of the Na enol salt of MDA in the drinking water of mice over a range of 0.1-10.0 micrograms/g/day for 12 mo produced dose-dependent hyperplastic and neoplastic changes in liver nuclei and increased mortality at the highest level but produced no gross hepatic tumors. Addition of MDA to the medium of rat skin fibroblasts grown in culture caused nuclear abnormalities at concentrations as low as 10(-6) M despite an uptake of only 4%. [1,3-14C]MDA was rapidly oxidized to [14C]acetate in rat liver mitochondria and to 14CO2 in vivo; however, approximately 10% of the radioactivity was recovered in the urine. Chromatographic analysis of rat urine revealed the presence of several compounds which yield MDA on acid hydrolysis. Total MDA excretion increased in response to conditions which stimulate lipid peroxidation in vivo, including vitamin E deficiency, Fe or CCl4 administration, and enrichment of the tissues with PUFA. N-acetyl-e-(2-propenal)lysine was identified as a major urinary metabolite of MDA in rat and human urine. This compound is derived primarily from N-alpha-(2-propenal)lysine released in digestion as a product of reactions between MDA and the epsilon-amino groups of N-terminal lysine residues in food proteins. However, its presence in the urine of animals fasted or fed MDA-free diets indicates that it is also formed in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Identification of N alpha-acetyl-epsilon-(2-propenal)lysine as a urinary metabolite of malondialdehyde.
Although orally administered malondialdehyde (MDA), a reactive hepatotoxic and mutagenic product of lipid peroxidation, is extensively metabolized to CO2, a portion is excreted in the urine in acid labile "bound" forms. Since much of the MDA in the diet is apparently bound to protein, the metabolism of protein-bound MDA was investigated. MDA was reacted with serum albumin and fed to rats. A urinary metabolite was detected which was shown to be identical to a metabolite of the lysine-MDA enaminal N epsilon-(2-propenal)lysine. After isolation by ion exchange and high performance liquid chromatography the metabolite was identified using high field nuclear magnetic resonance spectroscopy and fast atom bombardment-mass spectroscopy as N alpha-acetyl-epsilon-(2-propenal)lysine. This compound also was a major urinary metabolite of the Na enol salt of MDA administered by stomach intubation, and was excreted in increased amounts by rats fed a diet containing a highly peroxidizable oil (cod liver oil). It was also detected in the urine of fasted animals after injection with NaMDA, indicating that it is formed as a product of lipid peroxidation in vivo as well as of peroxidation of dietary lipids.
Animals↗
Animal models for the study of nutrition and human disease: colon cancer, atherosclerosis, and osteoporosis.
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Animals↗
Urinary malondialdehyde as an indicator of lipid peroxidation in the diet and in the tissues.
Although malondialdehyde (MDA) is extensively metabolized to CO2, small amounts are nevertheless excreted in an acid-hydrolyzable form in rat urine. In this study, urinary MDA was evaluated as an indicator of lipid peroxidation in the diet and in the tissues. MDA was released from its bound form(s) in urine by acid treatment and determined as the TBA-MA derivative by HPLC. MDA excretion by the rat was found to be responsive to oral administration of the Na enol salt and to peroxidation of dietary lipids. Urinary MDA also increased in response to the increased lipid peroxidation in vivo produced by vitamin E deficiency and by administration of iron nitrilotriacetate. Chronic feeding of a diet containing cod liver oil led to increases in MDA excretion which were not completely eliminated by fasting or feeding a peroxide-free diet, indicating that there was increased lipid peroxidation in vivo. MDA excretion was not responsive to Se deficiency or CCl4 administration. DPPD, a biologically active antioxidant, but not BHA, a non-biologically active antioxidant, prevented the increase in MDA excretion in vitamin E deficient animals. The results indicate that MDA excretion can serve as an indicator of the extent of lipid peroxidation in the diet and, under conditions which preclude a dietary effect, as an index of lipid peroxidation in vivo.
Animals↗
Comparative studies on different methods of malonaldehyde determination.
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Animals↗
Self-regulation of phosphate intake in the rat: the influence of age, vitamin D and parathyroid hormone.
Growing rats offered a choice of four pairs of diets, one low in P (0.1%) and the others containing 0.3, 0.6, 1.2 or 1.8% P, selected food mixtures in each case with nearly identical P contents (0.23-0.24%) (Ca:P = 2.2:1). Mature rats offered the same dietary choices exhibited less rigid diet selection but clearly preferred a diet higher in P (0.64-0.69%) (Ca:P = 0.9:1). Vitamin D-deficient animals selected less P than controls and parathyroidectomized rats severely limited their P intake. The increase in self-determined P consumption relative to Ca in mature rats is consonant with the greater decrease in the requirement for Ca associated with maturation and cessation of bone growth. Susceptibility to hypocalcemia in vitamin D deficiency and parathyroidectomy is a probable factor in the increased sensitivity to excess dietary P, which further depresses plasma Ca. These experiments confirm the existence of a feedback mechanism that regulates the voluntary consumption of P in accordance with physiological needs.
Aging↗
Determination of malonaldehyde in biological materials by high-pressure liquid chromatography.
An HPLC method is described for the determination of malonaldehyde in biological materials. The procedure involves extracting the sample with trichloracetic acid, heating the extract with thiobarbituric acid, separating the thiobarbituric acid-malonaldehyde complex on a mu Bondapak C18 column, and measuring the absorbance using a 546-nm interference filter. The method was found to be specific for malonaldehyde in several food and feed samples. Under routine assay conditions, a coefficient of variability of 7.0% was obtained for samples containing 1-2 microgram of malonaldehyde per gram (instrument detection limit 1 ng). This procedure yields lower values for the concentration of malonaldehyde in food samples than the conventional spectrophotometric procedure based on absorbance of the thiobarbituric acid-malonaldehyde complex at 532 nm.
Animal Feed↗
Oral toxicity of malonaldehyde: a 90-day study on mice.
The oral toxicity of malonaldehyde (MA), a product of lipid peroxidation found in some foods, was investigated in a 90-d study on mice, MA as the sodium enol salt was administered in the drinking water to 8-wk-old female Swiss mice at levels calculated to provide 2, 10, 50, 250, or 500 micrograms/g body weight . d. There was no mortality and all groups gained weight at comparable rates except that those that received 500 micrograms/g body weight . d gained more slowly and lost weight after 50 d. Histopathological examination of 27 tissues indicated that the liver was the only organ that underwent dose-dependent changes. All levels of MA induced irregularities (anisokaryosis, hyperchromicity, vesiculation) of hepatic nuclei. Pancreatic lesions consisting primarily of atrophy of the exocrine cells with loss of zymogen granulation occurred in animals which received 500 micrograms MA/g body weight . d. Mild dysplasia of the urinary bladder epithelium was found in all treatment groups. Approximately 1% of the dose was excreted unchanged in the urine at each level of administration.
Administration, Oral↗