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M Hadley

Publications and source records attributed to M Hadley.

34 records · Page 2Linked to original sources
PubMed1990

A review of recent studies on the metabolism of exogenous and endogenous malondialdehyde.

1. The generation of malondialdehyde (MDA), a mutagenic product of the oxidative decomposition of highly unsaturated fatty acids in vivo, is increased by exposure to certain environmental oxidants and xenobiotics. 2. This increase is reflected in enhanced excretion of several MDA derivatives in the urine. The main urinary metabolites of MDA have been identified as N-epsilon-(2-propenal)lysine and its N-alpha-acetyl ester. 3. Two minor metabolites have been identified as enaminals formed by reactions with the phospholipid bases serine and ethanolamine. A further MDA metabolite has been identified as a cyclized adduct with guanine. 4. These urinary compounds reflect the turnover of proteins, phospholipids and nucleic acids that have been modified by reactions with MDA in vivo. Monitoring of the urinary adduct with guanine may provide a practicable method of assessing the effect of xenobiotics and other factors on in vivo lipid peroxidation. 5. The proportion of total MDA in the diet, blood, urine and solid tissues that exists in the free state appears to be negligible. 6. Chronic oral administration of the enol Na salt of MDA to animals produced no significant pathology except for dose-dependent lesions of hepatic nuclei. Nuclear abnormalities in cultured rat skin fibroblasts were seen at intracellular concentrations as low as 10(-7) M.

Animals↗
PubMed1989

Identification of N-(2-propenal)ethanolamine as a urinary metabolite of malondialdehyde.

N-(2-propenal)ethanolamine was isolated from rat and human urine using anion exchange, cation exchange, size exclusion and high performance liquid chromatography. Acid hydrolysis of the isolate yielded malondialdehyde (MDA) and ethanolamine (E) in a 1:1 molar ratio. A 1:1 E-MDA adduct was synthesized and found to be chromatographically inseparable from the urinary metabolite. Its NMR and UV spectra and lack of fluorescence were consistent with those of an enaminal formed by a Schiff's base reaction. The identification in urine of an adduct of MDA with ethanolamine, and the previous identification of an adduct with serine, constitutes direct evidence for the oxidative decomposition in vivo of polyunsaturated fatty acids present in the relevant phospholipids. The absence in urine of MDA adducts with other alpha-amino compounds (at least in comparable amounts) indicates that the ethanolamine and serine derivatives are formed in situ and not as a result of reactions with MDA generated in enzymatic processes.

Animals↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1983

Light microscopic autoradiographic visualization of [3H]-arginine vasopressin binding sites in rat brain.

Specific [3H]-arginine vasopressin ([3H]-AVP) binding sites were identified in the rat brain by light microscopic autoradiography. Discrete intrahypothalamic nuclei were densely labelled by [3H]-AVP. High specific binding was observed in the paraventricular and supraoptic nuclei. These binding sites may represent specific receptors for AVP, postulated to exist in the mammalian central nervous system.

Animals↗
PubMed1983

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↗
PubMed1981

Self-regulation of phosphate intake by growing rats.

Groups of growing rats (100-150 g) were offered a choice of two diets, one containing a deficient concentration of phosphorus (0.1%) and the other containing 0.3, 0.6, 1.2 or 1.8% phosphorus. All diets contained 0.6% Ca and were isocaloric. Except for the groups that were offered the 0.1 and 0.3% phosphorus diets, all the animals selected mixtures of diets containing nearly identical phosphorus contents (0.33-0.36%). The group offered the two diets lowest in phosphorus selected 83% of their food from the higher (0.3%) phosphorus diet to obtain a mixture containing 0.25% phosphorus. Irrespective of the phosphorus content of the diets available, all groups ate similar amounts of food, made similar weight gains and maintained normal plasma levels of calcium and phosphorus. The experiment demonstrates the existence of a feedback mechanism by which growing rats regulate their phosphorus intake within narrow limits when allowed to self-select among diets of markedly different phosphorus contents. It is postulated that feedback regulation of phosphorus intake is mediated by changes in plasma calcium homeostasis.

Animals↗
PubMedDate not supplied

Partial characterization of IR-alpha-MSH peptides found in melanoma tumors.

Our previous work indicated that IR-alpha-MSH (immunoreactive alpha-melanocyte-stimulating hormone) plasma levels are three times as high in melanoma patients with progressing disease than in disease-free patients, and that the melanoma tumor itself may be the source of IR-alpha-MSH. Further identification of the material in tumor extracts has been carried out in this study, and the results presented here show that the immunoreactivity is associated with a major fraction of about 16 kDa and another of 5-9 kDa. Significant amounts of the immunoreactive material were also found in human melanoma cells but not in culture supernatants. The presence of this material may be related to the melanogenic status of the tumor cells. We have estimated the intracellular IR-alpha-MSH to be within a 0.4 to 2.3 nM range in melanoma tumor cells. We have investigated the melanogenic effect of the IR-alpha-MSH material and its relationship to alpha-MSH. Purified extracts both from metastases and cultured cells were found to promote frog skin darkening as well as tyrosinase activity in Cloudman S91 melanoma cells. The IR material could also displace labeled alpha-MSH from its binding sites in human melanoma cells. Our data clearly indicate that melanoma cells engage in an autocrine production of alpha-MSH-like bioactive peptides by melanoma cells, of larger mol.wt., which are able to bind to MSH receptors. These peptides may be involved in the regulation of melanogenesis and possibly in the growth and proliferation of melanoma cells by an autocrine/paracrine mechanism.

Adult↗