Renal toxicity of nε-(dl-2-amino-2-carboxyethyl)-l-lysine (lysinoalanine) in rats

Woodard, J. C.; Short, D.D.

doi:10.1016/s0015-6264(77)80316-7

Cited by 31 publications

(3 citation statements)

References 7 publications

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“…The renal damage seen following HCBD is similar to that described with a number of other nephrotoxic agents in the rat such as mercuric chloride (Gritzka and Trump, 1968;McDowell et al, 1976), dl-serine (Wachstein, 1947;Wachstein and Besen, 1964), dl-ethionine (Wachstein and Meisel,195 l), lysinoalanine (Woodard and Short, 1976) and cis-platinum (Dobyan et al, 1980). All these compounds produce necrosis of the pars recta or S, portion of the proximal tubule.…”

Section: Discussionsupporting

confidence: 62%

Necrosis of the pars recta (S₃ segment) of the rat kidney produced by hexachloro 1:3 butadiene

Ishmael¹,

Pratt²,

Lock³

1982

The Journal of Pathology

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Administration of hexachloro 1:3 butadiene (HCBD) intraperitoneally at a dose of 200 mg/kg body weight caused necrosis of the parts recta of the proximal tubules situated in the outer stripe of the outer medulla of the rat kidney. The earliest morphological changes detectable by light microscopy were observed after eight hours, with several proximal tubules showing necrosis. By sixteen hours a distinct band of tubular necrosis was seen in the outer stripe of the outer medulla. One and two days after dosing proximal tubular necrosis was still evident whereas distal tubules were unaffected. By three days, vacuolation was observed in the pars convoluta of some proximal tubules. Active tubular regeneration was apparent by day five, which was accompanied by a marked increase in renal water and nonprotein sulphydryl content (NP-SH). By day fourteen substantial recovery had occurred. Ultrastructural changes were seen as early as one hour after HCBD (300 mg/kg, ip) although necrosis was not marked until 8 hr. Mitochondrial swelling was seen 1-4 hr after dosing in the S1 and S2 segments of the proximal tubule. By 8 hr the major pathological changes were largely confined to the S2 segment and consisted of loss of brush border, mitochondrial swelling and cellular necrosis. In conclusion HCBD produces a site-specific nephrotoxic effect on the proximal tubule in the rat. The pattern of injury was similar to that associated with some other nephrotoxic and ischaemic models of acute renal failure.

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Section: Discussionsupporting

confidence: 62%

Necrosis of the pars recta (S₃ segment) of the rat kidney produced by hexachloro 1:3 butadiene

Ishmael¹,

Pratt²,

Lock³

1982

The Journal of Pathology

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“…Enlarged nuclei have been reported in rats by feeding as little as 1200–1400 ppm protein- bound LAL ( 74 , 75 ) . In comparison, feeding of free LAL was found to produce nephrocytomegaly at much lower levels (100–250 ppm) ( 76 , 77 ) . L-lysyl-D-alanyl-LAL, the most potent isomer of the four optical isomers of LAL, induced nephrocytomegaly when fed at levels as low as 30 ppm, whereas D-lysyl-D-alanyl-lysinoalanine did not produce lesions at less than 1000 ppm ( 78 ) .…”

Section: Protein-bound D-amino Acids and Lysinoalanine (Lal)mentioning

confidence: 99%

Impact of Antinutritional Factors in Food Proteins on the Digestibility of Protein and the Bioavailability of Amino Acids and on Protein Quality

2012

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Dietary antinutritional factors have been reported to adversely affect the digestibility of protein, bioavailability of amino acids and protein quality of foods. Published data on these negative effects of major dietary antinutritional factors are summarized in this manuscript. Digestibility and the quality of mixed diets in developing countries are considerably lower than of those in developed regions. For example, the digestibility of protein in traditional diets from developing countries such as India, Guatemala and Brazil is considerably lower compared to that of protein in typical North American diets (54 -78 versus 88-94 %). Poor digestibility of protein in the diets of developing countries, which are based on less refined cereals and grain legumes as major sources of protein, is due to the presence of less digestible protein fractions, high levels of insoluble fibre, and/or high concentrations of antinutritional factors present endogenously or formed during processing. Examples of naturally occurring antinutritional factors include glucosinolates in mustard and canola protein products, trypsin inhibitors and haemagglutinins in legumes, tannins in legumes and cereals, gossypol in cottonseed protein products, and uricogenic nucleobases in yeast protein products. Heat/alkaline treatments of protein products may yield Maillard reaction compounds, oxidized forms of sulphur amino acids, D-amino acids and lysinoalanine (LAL, an unnatural nephrotoxic amino acid derivative). Among common food and feed protein products, soyabeans are the most concentrated source of trypsin inhibitors. The presence of high levels of dietary trypsin inhibitors from soyabeans, kidney beans or other grain legumes have been reported to cause substantial reductions in protein and amino acid digestibility (up to 50 %) and protein quality (up to 100 %) in rats and/or pigs. Similarly, the presence of high levels of tannins in sorghum and other cereals, fababean and other grain legumes can cause significant reductions (up to 23 %) in protein and amino acid digestibility in rats, poultry, and pigs. Normally encountered levels of phytates in cereals and legumes can reduce protein and amino acid digestibility by up to 10 %. D-amino acids and LAL formed during alkaline/heat treatment of lactalbumin, casein, soya protein or wheat protein are poorly digestible (less than 40 %), and their presence can reduce protein digestibility by up to 28 % in rats and pigs, and can cause a drastic reduction (100 %) in protein quality, as measured by rat growth methods. The adverse effects of antinutritional factors on protein digestibility and protein quality have been reported to be more pronounced in elderly rats (20-months old) compared to young (5-weeks old) rats, suggesting the use of old rats as a model for assessing the protein digestibility of products intended for the elderly.

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“…Les protéines ayant subi un traitement alcalin relativement sévère sont toujours considérées comme étant sans toxicité (Nashef ei al., 1977), malgré la formation de lysinoalanine (N E -(DL-2-amino-2-carboxyethyl)-L-Lysine) dont la néphrotoxicité a été bien démontrée chez le rat (Woodard et Short, 1976) …”

Section: Introductionunclassified

Transit digestif chez le rat recevant de la caséine traitée en milieu alcalin

Possompes¹,

Schin²,

Besançon³

1979

Ann. Biol. anim. Bioch. Biophys.

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Renal toxicity of nε-(dl-2-amino-2-carboxyethyl)-l-lysine (lysinoalanine) in rats

Cited by 31 publications

References 7 publications

Necrosis of the pars recta (S₃ segment) of the rat kidney produced by hexachloro 1:3 butadiene

Necrosis of the pars recta (S₃ segment) of the rat kidney produced by hexachloro 1:3 butadiene

Impact of Antinutritional Factors in Food Proteins on the Digestibility of Protein and the Bioavailability of Amino Acids and on Protein Quality

Transit digestif chez le rat recevant de la caséine traitée en milieu alcalin

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Renal toxicity of nε-(dl-2-amino-2-carboxyethyl)-l-lysine (lysinoalanine) in rats

Cited by 31 publications

References 7 publications

Necrosis of the pars recta (S3 segment) of the rat kidney produced by hexachloro 1:3 butadiene

Necrosis of the pars recta (S3 segment) of the rat kidney produced by hexachloro 1:3 butadiene

Impact of Antinutritional Factors in Food Proteins on the Digestibility of Protein and the Bioavailability of Amino Acids and on Protein Quality

Transit digestif chez le rat recevant de la caséine traitée en milieu alcalin

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Necrosis of the pars recta (S₃ segment) of the rat kidney produced by hexachloro 1:3 butadiene

Necrosis of the pars recta (S₃ segment) of the rat kidney produced by hexachloro 1:3 butadiene