Chloropropionic acid-induced alterations in glucose metabolic status: possible relevance to cerebellar granule cell necrosis.
We have examined the effect of L- and D-2-chloropropionic acid (L-CPA and D-CPA) on the concentrations of pyruvate, lactate, glucose and beta-hydroxybutyrate in the blood at various times after doses which produce cerebellar granule cell necrosis. Blood pyruvate and lactate concentrations were reduced in these animals 4 h after dosing and remained below those of controls for up to 48 h. No changes were seen in concentrations of plasma glucose of beta-hydroxybutyrate at any time point. Similarly, no changes in cerebellar glucose, pyruvate or lactate were seen 24 h after 750 mg/kg L-CPA. Oxidation of [14C] pyruvate or [14C] glucose to [14CO2] by cerebellar slices from control rats was not altered by the presence of L- or D-CPA (1-10 mM for 2 h). Nor were these parameters affected in cerebellar slices from rats killed 24 h after a dose of 750 mg/kg L-CPA. We conclude that the activation of the pyruvate dehydrogenase complex is unlikely to be a critical factor in the selective toxicity of CPA to the cerebellum.
Lock
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EA
Neurotoxicology Group, Zeneca Central Toxicology Laboratory, Cheshire, UK.
Gyte
A
A
Widdowson
P
P
Simpson
M
M
Wyatt
I
I
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D003594:Cytoplasmic Granules / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism*; D006843:Hydrocarbons, Chlorinated; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009336:Necrosis; D011422:Propionates / Q000633:toxicity*; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D006843:Hydrocarbons, Chlorinated; D007773:Lactates; D011422:Propionates; D011773:Pyruvates; D019344:Lactic Acid; D019289:Pyruvic Acid; C021974:2-chloropropionic acid; D005947:Glucose