title: Protective activity of α-lactoalbumin (ALAC), a whey protein rich in tryptophan, in rodent models of epileptogenesis.
abstract: The aim of the present work was to evaluate the potential activity of α-lactoalbumin (ALAC), a whey protein rich in tryptophan (TRP), in two rodent models of epileptogenesis and we explored a possible mechanism of action. The effects of ALAC (oral administration) were tested in two standard epileptogenesis protocols, namely the pilocarpine post-status epilepticus model in mice and the WAG/Rij rat model of absence epileptogenesis. The mechanism of action was investigated by assessing the effects of ALAC in two seizure models (N-methyl-d-aspartate (NMDA) and pentylenetetrazol (PTZ) -induced seizures) including d-serine co-administration. ALAC showed protecting properties in both models of epileptogenesis, reducing spontaneous seizures development. In acute seizure models, ALAC possessed antiseizure properties at some of the doses tested (PTZ-seizures: >50% seizure-reduction between 250 and 375 mg/kg; NMDA-seizures: >90% reduction at 250 and 500 mg/kg). When a dose of d-serine ineffective per se was co-administered with ALAC, ALAC effects were significantly reversed in both models. ALAC is active in experimental models of seizure and epileptogenesis. Its effects are likely mediated by the inhibition of NMDA receptors at the glycine binding site, possibly secondarily to the in vivo enzymatic conversion of ALAC-generated tryptophan to kynurenic acid. However, other mechanisms of action contributing to ALAC effects cannot be excluded.
authors.affiliation: Science of Health Department, School of Medicine, University Magna Graecia of Catanzaro, Italy. erusso@unicz.it
authors.forename: E
authors.initials: E
authors.lastname: Russo
authors.forename: F
authors.initials: F
authors.lastname: Scicchitano
authors.forename: R
authors.initials: R
authors.lastname: Citraro
authors.forename: R
authors.initials: R
authors.lastname: Aiello
authors.forename: C
authors.initials: C
authors.lastname: Camastra
authors.forename: P
authors.initials: P
authors.lastname: Mainardi
authors.forename: S
authors.initials: S
authors.lastname: Chimirri
authors.forename: E
authors.initials: E
authors.lastname: Perucca
authors.forename: G
authors.initials: G
authors.lastname: Donato
authors.forename: G
authors.initials: G
authors.lastname: De Sarro
mesh_terms: D000818:Animals; D003292:Convulsants; D004827:Epilepsy / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D004832:Epilepsy, Absence / Q000139:chemically induced / Q000517:prevention & control; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D006624:Hippocampus / Q000473:pathology; D007736:Kynurenic Acid; D007768:Lactalbumin / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008894:Milk Proteins / Q000737:chemistry / Q000494:pharmacology*; D016202:N-Methylaspartate; D010433:Pentylenetetrazole; D010862:Pilocarpine; D051381:Rats; D014364:Tryptophan / Q000737:chemistry / Q000494:pharmacology*; D000067816:Whey Proteins
chemical_list: D003292:Convulsants; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D008894:Milk Proteins; D000067816:Whey Proteins; D010862:Pilocarpine; D016202:N-Methylaspartate; D014364:Tryptophan; D007768:Lactalbumin; D007736:Kynurenic Acid; D010433:Pentylenetetrazole