Glycine modulates the toxicity of benzyl acetate in F344 rats.
The influence of supplemental glycine on benzyl acetate (BA; a compound metabolized via the hippurate pathway)-induced toxicity was investigated. Groups of male F344 rats were fed NIH-07 diet containing 0, 20,000, 35,000, or 50,000 ppm BA for up to 28 days. Two additional groups were fed NIH-07 diet with 50,000 ppm BA and 27,000 ppm glycine or 50,000 ppm BA 32,000 ppm L-alanine; supplemental glycine and L-alanine were equimolar. The L-alanine group served as an amino nitrogen control. A third group was fed NIH-07 diet with 32,000 ppm L-alanine and served as an untreated isonitrogenous control BA caused increase in mortality, body weight loss, the incidence of abnormal neurobehavioral signs such as ataxia and convulsions, along with astrocyte hypertrophy and neuronal necrosis in the cerebellum, hippocampus, and pyriform cortex of the brain. These effects were reduced significantly by supplementation with glycine but not with L-alanine. These results suggest that the neurodegeneration induced by BA is mediated by a depletion of the glycine pool and the subsequent excitotoxicity.
Abdo
K M
KM
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. abdok@niehs.nih.gov
Wenk
M L
ML
Harry
G J
GJ
Mahler
J
J
Goehl
T J
TJ
Irwin
R D
RD
D000395:Air Pollutants, Occupational / Q000009:adverse effects; D000818:Animals; D001259:Ataxia / Q000139:chemically induced / Q000517:prevention & control; D001593:Benzyl Compounds / Q000009:adverse effects*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000008:administration & dosage / Q000494:pharmacology*; D006984:Hypertrophy / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D009336:Necrosis; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D015996:Survival Rate; D015431:Weight Loss / Q000187:drug effects
D000395:Air Pollutants, Occupational; D001593:Benzyl Compounds; C046412:benzyl acetate; D005998:Glycine