Inducibility of AhR-regulated CYP genes by β-naphthoflavone in the liver, lung, kidney and heart of the pig

Chirulli, V.; Marvasi, Luigi; Zaghini, Anna; Fiorio, R.; Longo, Vincenzo; Gervasi, Pier Giovanni

doi:10.1016/j.tox.2007.07.015

Cited by 32 publications

(22 citation statements)

References 47 publications

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“…Szotá ková et al (2004) found higher activities of those enzymes in six entire male pigs (Landrace) at the age of 7 to 9 months (95 1 16 pmol/min per mg of protein for EROD, and 26 1 8 pmol/min per mg of protein for MROD). PROD activities in the present study were lower compared with those found by Chirulli et al (2007). In contrast, Monshouwer et al (1998) and Anzenbacher et al (1998) could not detect PROD activity in cultured pig hepatocytes and minipig liver microsomes, respectively.…”

Section: Discussioncontrasting

confidence: 90%

Modulation of porcine cytochrome P450 enzyme activities by surgical castration and immunocastration

Zamaratskaia

Žlábek

Chen

et al. 2009

Animal

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The present study aimed to evaluate some cytochrome P450 metabolic enzyme activities in hepatic microsomes prepared from entire male pigs (uncastrated pigs), surgically castrated pigs and pigs immunized against gonadotropin-releasing hormone (immunocastrated pigs). The activities of the following enzymes were measured: ethoxyresorufin O-deethylase (EROD, CYP1A1/ 1A2), methoxyresorufin O-deethylase (MROD, CYP1A2), pentoxyresorufin O-depentylase (PROD, CYP2B), coumarin hydroxylase (COH, CYP2A) and p-nitrophenol hydroxylase (PNPH, CYP2A/2E1). The total cytochrome P450 contents were not affected by either surgical or immunocastration. Hepatic microsomal activities for EROD, PROD, COH and PNPH were lower in entire male pigs compared with surgically castrated and immunocastrated pigs ( P , 0.05). Surgically and immunocastrated male pigs were similar with respect to EROD, MROD, PROD and COH activities ( P . 0.05), whereas surgically castrated pigs exhibited lower PNPH activity compared with immunocastrated pigs ( P 5 0.029). The effect of different concentrations of testicular steroidstestosterone, 17b-estradiol, free estrone and androstenone -on enzyme activities was evaluated by in vitro microsomal study. Testosterone at the concentration of 8 pmol/ml inhibited EROD activities and estradiol-17b at the concentration of 1.8 pmol/ml inhibited PROD activities in hepatic microsomes from surgically castrated pigs. The highest concentration of androstenone (7520 pmol/ml) inhibited COH activities, whereas a 42-fold lower concentration of androstenone (180 pmol/ml) stimulated COH activities in surgically castrated pigs. Both free estrone (3.5 pmol/ml) and androstenone (55 pmol/ml) inhibited EROD activities in microsomes from entire male pigs. Stimulation of COH activities by the highest dose of free estrone (18 pmol/ml) was recorded in microsomes from entire male pigs. However, these effects of steroids were not concentration-dependent and the maximum extent did not exceed 615% variation compared with the controls. There was no inhibition of PNPH activities in the hepatic microsomes from either entire or castrated pigs. In conclusion, we showed that EROD, PROD, COH and PNPH activities were lower in entire male pigs compared with those in surgically and immunocastrated pigs. Direct inhibition by the testicular steroids -testosterone, 17b-estradiol, free estrone and androstenone -was not the primary cause of the reduced enzyme activities.Keywords: castration, cytochrome P450, porcine liver microsomes, steroids ImplicationsThe present study evaluated some cytochrome P450 enzyme activities in liver microsomes from uncastrated male pigs, surgically castrated pigs and pigs immunized against gonadotropin-releasing hormone (immunocastrated pigs). We found that CYP1A1, CYP2A, CYP2B and CYP2E1 activities were lower in uncastrated male pigs compared with surgically castrated and immunocastrated pigs. These findings strengthen the hypothesis of testicular steroid involvement in cytochrome P450 enzyme regulation. The differences in the ac...

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Section: Discussioncontrasting

confidence: 90%

Modulation of porcine cytochrome P450 enzyme activities by surgical castration and immunocastration

Zamaratskaia

Žlábek

Chen

et al. 2009

Animal

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“…As previously reported (Chirulli et al, 2007), ␤NF treatment caused a strong increase of EROD and MEROD activities in liver microsomes, whereas in the respiratory and olfactory microsomes only EROD activity, although at a low extent (about twofold), was significantly enhanced (Table 3). On the other hand, the CoH and AnH activities in the hepatic and nasal mucosa microsomes were not affected by ␤NF.…”

Section: Effect Ofˇnf and Rif On Cyp Activities In Hepatic Respiratosupporting

confidence: 84%

“…CYP1A2 is primarily a liver enzyme (Shimada et al, 2002), however, a high expression of this CYP in the olfactory mucosa of rodents has also been reported (Ling et al, 2004). At variance, the constitutive expression of CYP1B1 mRNA, as determined by realtime PCR, was found quite similar in liver and both nasal tissues; their expression levels, however, are low as a previous analysis by qualitative RT-PCR missed to detect this transcript in liver (Chirulli et al, 2007).…”

Section: Discussionmentioning

confidence: 72%

Expression and inducibility of CYP1A1, 1A2, 1B1 by β-naphthoflavone and CYP2B22, 3A22, 3A29, 3A46 by rifampicin in the respiratory and olfactory mucosa of pig

et al. 2009

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“…MROD seems to be more dependent on CYP1A2 activity than EROD (Messina et al. 2008), whilst EROD seems to be more specific towards CYP1A1 activity (Chirulli et al. 2007).…”

Section: Discussionmentioning

confidence: 99%

Gender‐related Differences in Cytochrome P450 in Porcine Liver – Implication for Activity, Expression and Inhibition by Testicular Steroids

Rasmussen

Zamaratskaia

Ekstrand

2010

Reprod Domestic Animals

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In pigs, the hepatic cytochrome P450 (CYP) 1A2, 2A and 2E1 activity is important in the regulation of skatole accumulation in adipose tissue. This study investigated gender-related differences in CYP1A2, 2A and 2E1 dependent activity, protein and mRNA expression. This study also investigated the gonadal steroid dependent inhibition of CYP activity in relation to gender and dietary composition. Microsomes were prepared from the liver of female and entire male pigs (Landrace × Yorkshire sire and Duroc boars) reared under similar conditions and slaughtered at an age of 164 days. A group of entire male pigs fed dried chicory root for 16 days prior to slaughter were included in the study. CYP activities were assessed by the use of probe substrates, whilst mRNA and protein expression were analysed by RT-PCR and Western blotting. Furthermore inhibition of CYP dependent activity by gonadal steroids was assessed in vitro. Microsomes from female pigs had greater CYP1A2 and 2A activity, as well as mRNA expression compared to entire male pigs. The antibodies used did not detected differences in protein expression. In vitro inhibition by 17β-oestradiol, oestrone, androstenone and 3β-OH androstenol of CYP2E1 activity in microsomes from entire male pigs as well as inhibition of CYP1A activity in chicory fed entire male pigs was observed. Apart from that no effect of steroids was shown. In conclusion, female pigs show greater CYP activity and mRNA expression. Including chicory in the diet for 16 days changed the gonadal steroid dependent inhibition of CYP activity in entire male pigs.

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Inducibility of AhR-regulated CYP genes by β-naphthoflavone in the liver, lung, kidney and heart of the pig

Cited by 32 publications

References 47 publications

Modulation of porcine cytochrome P450 enzyme activities by surgical castration and immunocastration

Modulation of porcine cytochrome P450 enzyme activities by surgical castration and immunocastration

Expression and inducibility of CYP1A1, 1A2, 1B1 by β-naphthoflavone and CYP2B22, 3A22, 3A29, 3A46 by rifampicin in the respiratory and olfactory mucosa of pig

Gender‐related Differences in Cytochrome P450 in Porcine Liver – Implication for Activity, Expression and Inhibition by Testicular Steroids

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