Acute and repeated dose (4 weeks) oral toxicity studies of two antihypertensive peptides, RYLGY and AYFYPEL, that correspond to fragments (90-94) and (143-149) from alpha(s1)-casein.
The Lowpept is a powdered casein hydrolysate containing the antihypertensive peptides RYLGY and AYFYPEL, two sequences that correspond to alpha(s1)-casein f (90-94) (RYLGY) and alpha(s1)-casein f (143-149) (AYFYPEL). To support the safety, Lowpept has been examined in an acute and in a 4-week repeated dose oral toxicity studies in rats. Powdered casein hydrolysate administered in a single oral gavage dose of 2000 mg/kg resulted in no adverse events or mortality. Also, casein hydrolysate administered as a daily dose of 1000 mg/kg for 4 weeks by gavage resulted in no adverse events or mortality. No evidence or treatment-related toxicity was detected during both studies. Data analysis of body weight gain, food consumption, clinical observations, blood biochemical, haematology, organ weight ratios and histopathological findings did not show significant differences between control and treated groups. It is concluded that the casein hydrolysate containing the peptides RYLGY and AYFYPEL orally administered to rats was safe and that not treatment-related toxicity was detected even at the highest doses investigated in both acute (2000 mg/kg of body weight) and repeated dose (4 weeks) oral (1000 mg/kg of body weight) toxicity studies.
Anadón
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A
Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain. anadon@vet.ucm.es
Martínez
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MA
Ares
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I
Ramos
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E
Martínez-Larrañaga
M R
MR
Contreras
M M
MM
Ramos
M
M
Recio
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D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000633:toxicity*; D001772:Blood Cell Count; D001774:Blood Chemical Analysis; D002364:Caseins / Q000737:chemistry / Q000633:toxicity*; D005260:Female; D006868:Hydrolysis; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010446:Peptide Fragments / Q000737:chemistry / Q000633:toxicity*; D011492:Protein Hydrolysates / Q000737:chemistry / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012727:Sex Characteristics; D015430:Weight Gain / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002364:Caseins; D010446:Peptide Fragments; D011492:Protein Hydrolysates; C553740:alpha(S1)-casein (143-149); C553739:alpha(S1)-casein (90-94)