A 90-day subchronic toxicity study and reproductive toxicity studies on ACE-inhibiting lactotripeptide.
In recent years there has been an increasing body of literature describing the antihypertensive effects of peptides produced from milk protein. The tripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP), isolated from hydrolysed casein have been shown to lower blood pressure by inhibiting angiotensin I-converting enzyme (ACE). This has led to the use of these tripeptides, collectively referred to as lactotripeptide (LTP) as ingredients of functional foods intended to help control blood pressure. A programme of studies including a 90-day repeat-dose oral gavage toxicity study in the rat and an embryo-fetal (pre-natal) development study in the rabbit was conducted to ensure the safety of this ACE-inhibiting ingredient. In addition, a non-standard pre- and post-natal development study in the rat was performed. This study included direct dosing of the neonates, and was designed specifically to investigate renal development and to ensure that the bioactive peptides were not associated with the same type of fetopathy exhibited by ACE inhibiting drugs. These studies showed that there were no adverse effects of treatment at the highest doses tested.
Dent
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Safety and Environmental Assurance Centre, Unilever Colworth, Sharnbrook, Bedford MK44 1LQ, UK. matthew.dent@unilever.com
O'Hagan
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Braun
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Schaetti
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Marburger
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Vogel
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D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D002712:Chlorides / Q000652:urine; D002784:Cholesterol / Q000097:blood; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000196:embryology; D008297:Male; D009842:Oligopeptides / Q000633:toxicity*; D011188:Potassium / Q000097:blood / Q000652:urine; D011817:Rabbits; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000187:drug effects; D012964:Sodium / Q000097:blood / Q000652:urine; D013047:Specific Pathogen-Free Organisms; D018709:Statistics, Nonparametric; D036401:Toxicity Tests, Chronic / Q000379:methods
D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D002712:Chlorides; D009842:Oligopeptides; C489032:isoleucyl-prolyl-proline; D000804:Angiotensin II; C489031:valyl-prolyl-proline; D000803:Angiotensin I; D002784:Cholesterol; D012964:Sodium; D011188:Potassium