Acute-phase response to benzo[a]pyrene and induction of rat ALDH3A1.
The aldehyde dehydrogenase-3A1 (ALDH3A1) enzyme, encoded by a member of the [Ah]-gene family, is dramatically increased (more than 100-fold) by benzo[a]pyrene (BaP) and other polycyclic hydrocarbons. Although much is known regarding the mechanism for the drug-metabolizing enzymes up-regulated by the Ah receptor, the physiological role of that tremendously increased ALDH3A1 enzyme activity is not yet fully clarified. The aim of this study was to identify a possible acute-phase response to different classes of xenobiotics affecting the metabolic capacity of the hepatocyte, by studying possible changes of serum acute-phase proteins (APPs) of hepatic origin, before and after BaP administration. Male Wistar rats were used in different series of experiments. The effects of BaP were estimated in terms of dose-response and time-response, with regard to the serum level of several APPs such as alpha-1-acid-glycoprotein (AAG), alpha-1-antitrypsin (AAT), C-reactive protein (CRP), and haptoglobin (HPT). In parallel experiments, levels of the same proteins have been determined after a time-dependent treatment with lipopolysaccharide (LPS). The changes in serum proteins were compared with the results of BaP or LPS administration on both hepatic ALDH3A1 and total ALDH enzyme activities. The results showed that BaP induced CRP and HPT in a time-dependent way, proportional to that caused by LPS. Additionally, ALDH3A1, CRP, and HPT were induced by BaP subacute treatment, whereas another type of ALDH inducer, phenobarbital, did not affect the levels of APPs or ALDH3A1, but did increase ALDH1A3 activity. Former studies of our group have shown that the inhibitory effects of different non-steroidal anti-inflammatory drugs (NSAIDs) on the ALDH3A1 induction were most possibly due to a decreased formation of arachidonic products like prostaglandins. Considering the changes of APPs caused by BaP, this study further supports the suggestion that the induction of ALDH3A1 is related to an atypical hepatocyte inflammation produced by xenobiotics.
Pappas
Periklis
P
Department of Pharmacology, Medical School, University of Ioannina, 45110, Ioannina, Greece. pappas@cc.uoi.gr
Sotiropoulou
Marianthi
M
Karamanakos
Petros
P
Kostoula
Aggeliki
A
Levidiotou
Stamatia
S
Marselos
Marios
M
D000209:Acute-Phase Proteins / Q000378:metabolism; D000210:Acute-Phase Reaction; D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D004790:Enzyme Induction; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000209:Acute-Phase Proteins; D000894:Anti-Inflammatory Agents, Non-Steroidal; C030863:corneal protein 54, bovine; D001564:Benzo(a)pyrene; D000444:Aldehyde Dehydrogenase