title: Inhibition of δ-aminolevulinate dehydratase is not closely related to the development of hyperglycemia in alloxan-induced diabetic mice.
abstract: Alloxan is a compound widely used in models of diabetes mellitus due to its ability for damage insulin-producing β-cells. The aim of this study was to investigate acute (after 24h) and sub-acute (after seven days) effects of 200mg/kg alloxan administration on mice. Biochemical parameters as liver, kidney, and blood δ-ALA-D activity, total sulfhydryl content of hepatic and renal tissues, and hepatic and renal content of malondialdehyde (MDA) were evaluated. The histopathology of hepatic and renal tissues of alloxan-treated and control animals was carried out. Further, blood glucose levels were determined in an attempt to correlate alloxan-induced hyperglycemia with changes in thiol status. Results showed that mice exhibited a significant inhibition of hepatic and renal δ-ALA-D activity in addition to a significant decrease in total sulfhydryl groups of same tissues in both acute and sub-acute alloxan administrations. Moreover, alloxan-induced inhibition of δ-ALA-D activity was partly suppressed when enzymatic assay was performed in the presence of dithiothreitol, suggesting that inhibitory effect of alloxan on δ-ALA-D activity is, at least partially, related to the oxidation of the enzyme's essential thiol groups. Blood δ-ALA-D activity was significantly inhibited only 24h after alloxan administration; however, at this time, a hyperglycemic status was not observed in animals. In contrast, a significant increase in blood glucose levels was observed seven days after alloxan administration. Despite of alterations in biochemical parameters, histological tissue examination of alloxan-treated mice revealed typical renal and hepatic parenchyma. Therefore, these results showed that acute toxic effects of alloxan are related, at least partially, to depletion of sulfhydryl groups, and do not closely relate to the development of hyperglycemia in mice.
authors.affiliation: Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, UFSM, CEP 97105-900 Santa Maria, RS, Brasil.
authors.forename: Verônica B
authors.initials: VB
authors.lastname: Brito
authors.forename: João Batista T
authors.initials: JB
authors.lastname: da Rocha
authors.forename: Gustavo O
authors.initials: GO
authors.lastname: Puntel
authors.forename: Sônia Cristina A
authors.initials: SC
authors.lastname: da Luz
authors.forename: Nilda B V
authors.initials: NB
authors.lastname: Barbosa
authors.forename: Nelson R
authors.initials: NR
authors.lastname: de Carvalho
authors.forename: Vanderlei
authors.initials: V
authors.lastname: Folmer
mesh_terms: D000496:Alloxan / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006943:Hyperglycemia / Q000097:blood / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors* / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004791:Enzyme Inhibitors; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D000496:Alloxan; D000623:Porphobilinogen Synthase