scholarly journals The Influence of Long-Term Treatment with Asenapine on Liver Cytochrome P450 Expression and Activity in the Rat. The Involvement of Different Mechanisms

2021 ◽  
Vol 14 (7) ◽  
pp. 629
Author(s):  
Przemysław J. Danek ◽  
Ewa Bromek ◽  
Władysława A. Daniel
Keyword(s):  
Growth Hormone ◽  
Cytochrome P450 ◽  
Term Treatment ◽  
Prolonged Treatment ◽  
Cytochrome P450 Enzymes ◽  
Protein Levels ◽  
Liver Cytochrome ◽  
Long Term Treatment ◽  
Expression And Activity

Therapy of schizophrenia requires long-term treatment with a relevant antipsychotic drug to achieve a therapeutic effect. The aim of the present study was to investigate the influence of prolonged treatment with the atypical neuroleptic asenapine on the expression and activity of rat cytochrome P450 (CYP) in the liver. The experiment was carried out on male Wistar rats. Asenapine (0.3 mg/kg s.c.) was administered for two weeks. The levels of CYP mRNA protein and activity were determined in the liver and hormone concentrations were measured in the pituitary gland and blood serum. Asenapine significantly decreased the activity of CYP1A (caffeine 8-hydroxylation and 3-N-demethylation), CYP2B, CYP2C11 and CYP3A (testosterone hydroxylation at positions 16β; 2α and 16α; 2β and 6β, respectively). The neuroleptic did not affect the activity of CYP2A (testosterone 7α-hydroxylation), CYP2C6 (warfarin 7-hydroxylation) and CYP2E1 (chlorzoxazone 6-hydroxylation). The mRNA and protein levels of CYP1A2, CYP2B1, CYP2C11 and CYP3A1 were decreased, while those of CYP2B2 and CYP3A2 were not changed. Simultaneously, pituitary level of growth hormone-releasing hormone and serum concentrations of growth hormone and corticosterone were reduced, while that of triiodothyronine was enhanced. In conclusion, chronic treatment with asenapine down-regulates liver cytochrome P450 enzymes, which involves neuroendocrine mechanisms. Thus, chronic asenapine treatment may slow the metabolism of CYP1A, CYP2B, CYP2C11 and CYP3A substrates (steroids and drugs). Since asenapine is metabolized by CYP1A and CYP3A, the neuroleptic may inhibit its own metabolism, therefore, the plasma concentration of asenapine in patients after prolonged treatment may be higher than expected based on a single dose.

Induction of Cardiac Cytochrome P450 in Cocaine-Treated Mice

2002 ◽  
Vol 227 (3) ◽  
pp. 182-188 ◽  
Author(s):  
Ju-Feng Wang ◽  
Yinke Yang ◽  
Matthew F. Sullivan ◽  
Jiangyong Min ◽  
Jinbo Cai ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cardiac Injury ◽  
Term Treatment ◽  
Cardiac Tissues ◽  
Protein Levels ◽  
Tnf Α ◽  
Long Term Treatment ◽  
P450 Expression ◽  
P450 Inhibitors

Cytochrome P450 (P450) is a ubiquitous family of enzymes responsible for the metabolism of a wide variety of drugs and their metabolites, including cocaine. To investigate the effects of cocaine on myocardial injuries and cardiac P450 expression, BALB/c mice were injected daily intraperitoneally with cocaine (30 mg/kg) or cocaine plus pretreatment of P450 inhibitors for 14 days. Tumor necrosis factor-α (TNF-α) content and creatine phosphokinase (CPK) activity in mice hearts and serums were significantly increased after long-term treatment with cocaine. Pretreatment with the P450 inhibitor, cimetidine (Cime, 50 mg/kg) or metyrapone (Mety, 40 mg/kg) abolished or significantly attenuated the effects of cocaine on TNF-α and CPK activity. Western blot analysis shows that mouse cardiac tissues express the P450 isoforms CYP1A1, CYP1A2, and CYP2J2. The protein levels normalized with cyclophilin A were 1.20 ± 0.07, 0.67 ± 0.03, and 1.48 ± 0.01 for CYP1A1, CYP1A2, and CYP 2J2, respectively. After cocaine administration, CYP2J2 increased by 43.6% and CYP1A1 increased by 108.5%, but CYP1A2 was not significantly altered. However, the cytochrome P450 inhibitors Cime and Mety suppressed the cocaine-induced increase in CYP1A1 and CYP2J2 expression. Moreover, application of Cime or Mety alone did not alter the level of cardiac TNF-α or the expression of P450. Our results demonstrate that long-term exposure to cocaine causes an increase in cardiac CYP1A1 and CYP2J2 concentration. We speculate that induction of P450 isoforms may cause cardiac injury due to cocaine metabolites locally catalyzed by P450 or the increase in P450 expression itself.

scholarly journals The effect of long-term treatment with steroid hormones or tamoxifen on oestrogen receptors (alpha and beta) in the endometrium of ovariectomized cynomolgus macaques

2002 ◽  
Vol 175 (3) ◽  
pp. 673-681 ◽  
Author(s):  
H Wang ◽  
E Isaksson ◽  
B Von Schoultz ◽  
JM Cline ◽  
L Sahlin
Keyword(s):  
Hormone Treatment ◽  
Term Treatment ◽  
Response To Treatment ◽  
Oestrogen Receptors ◽  
Minor Variation ◽  
Protein Levels ◽  
Long Term Treatment ◽  
High Level ◽  
Er Alpha

The effects of oestrogen are mediated by two specific intracellular receptors, oestrogen receptors (ER) alpha and beta, which function as ligand-activated transcriptional regulators. Ovariectomized macaques (Macaca fascicularis) were used to study the regulation of ERalpha and ERbeta in the endometrium by immunohistochemistry and in situ hybridization after long-term hormone treatment. Animals were treated continuously for 35 Months with either conjugated equine oestrogen (CEE), medroxyprogesterone acetate (MPA), combined CEE/MPA, or tamoxifen (TAM). Treatment with CEE/MPA down-regulated ERalpha in the superficial glands. In the superficial stroma the ERalpha level was lower in the CEE/MPA group than in the CEE and MPA groups. ERbeta immunostaining was faint with minor variation in response to treatment, but increased in the superficial stroma after MPA treatment. The ratio of ERbeta/ERalpha increased in superficial stroma and gland after CEE/MPA treatment, and also in stroma after MPA and TAM. Cystic endometrial hyperplasia was observed in TAM-treated animals, in combination with a high level of ERalpha protein expression. The present data show that long-term hormone treatment affects the ERalpha and ERbeta protein levels in the endometrium. The balance between ERalpha and ERbeta seems to be important for the proliferative response to oestrogen.

Hormonal changes in gilts receiving bromocriptine orally during gestation

2000 ◽  
Vol 80 (2) ◽  
pp. 373-376 ◽  
Author(s):  
S. Horth ◽  
C. Farmer
Keyword(s):  
Growth Hormone ◽  
Key Words ◽  
Initial Treatment ◽  
Term Treatment ◽  
Hormonal Changes ◽  
Long Term Treatment ◽  
Blood Profiles

Pregnant gilts received a placebo (CTL; n = 7) or 10 mg of bromocriptine orally (Bromo; n = 7) thrice daily from days 70 to 107 of gestation. Blood profiles of prolactin (PRL), growth hormone (GH) and cortisol were obtained on day 70, after the first treatment with bromocriptine, and on day 107 of gestation. On day 70, concentrations of PRL, GH and cortisol were not affected (P > 0.1) by bromocriptine. By day 107, bromocriptine decreased concentrations of PRL (P < 0.01) whereas concentrations of GH and cortisol were not affected (P > 0.1). Results indicate that long-term treatment with bromocriptine inhibits PRL secretion without affecting GH and cortisol concentrations, while no changes are present within 8 h of initial treatment. Key words: Gilt, gestation, bromocriptine, prolactin

Response of fat cells to growth hormone (GH): effect of long term treatment with recombinant human GH in GH-deficient adults.

1994 ◽  
Vol 78 (6) ◽  
pp. 1392-1395 ◽  
Author(s):  
I Harant ◽  
M Beauville ◽  
F Crampes ◽  
D Riviere ◽  
M T Tauber ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Term Treatment ◽  
Fat Cells ◽  
Long Term Treatment

Predicting the Response of Growth Hormone-Deficient Children to Long Term Treatment with Human Growth Hormone*

1979 ◽  
Vol 48 (3) ◽  
pp. 472-477 ◽  
Author(s):  
DANIEL RUDMAN ◽  
MICHAEL H. KUTNER ◽  
MARTIN A. GOLDSMITH ◽  
R.DWAIN BLACKSTON
Keyword(s):  
Growth Hormone ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Term Treatment ◽  
Long Term Treatment

Long-term treatment with growth hormone in short children with nephropathic cystinosis

2001 ◽  
Vol 138 (6) ◽  
pp. 880-887 ◽  
Author(s):  
Elke Wühl ◽  
Dieter Haffner ◽  
G. Offner ◽  
Michel Broyer ◽  
William van’t Hoff ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Term Treatment ◽  
Nephropathic Cystinosis ◽  
Short Children ◽  
Long Term Treatment
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