Gender-related differences in expression and function of hepatic P-glycoprotein and multidrug resistance-associated protein (Mrp2) in rats

Suzuki, Tatsuya; Zhao, Ying; Nadai, Masayuki; Naruhashi, Kazumasa; Shimizu, Aiko; Takagi, Kenji; Takagi, Kenzo; Hasegawa, Takaaki

doi:10.1016/j.lfs.2006.01.024

Cited by 60 publications

(57 citation statements)

References 26 publications

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“…It is possible that testosterone can reduce ABCC2 protein expression (P < 0.042) (Rost et al, 2005). Similar results were found in another rat study using western blot analysis (Suzuki et al, 2006). Suzuki et al (2006) showed that protein expression of ABCC2 was greater in female rats as compared to male rats, which was also reversely correlated with doxorubicin levels in liver cells.…”

Section: Comparing Levels Of Abcc2 Expression Between Males and Femalessupporting

confidence: 74%

“…Several factors may exert influence on the inter-individual variability of ABCC2 expression, including gestational age (Meyer et al, 2005), differences in cell cycle stages (van Der Kolk et al, 2001), ethnicity (Mor-Cohen et al 2012), single nucleotide polymorphisms (SNPs) (van Der Kolk et al, 2001;Meyer et al, 2005;Casobi, 2006;Deo et al, 2012) as well as gender (Rost et al, 2005.;Simon et al, 2006;Suzuki et al, 2006;MacLean et al, 2008). Studies have shown that expression of ABCC2 protein was 1.5 fold higher in female rat hepatocytes compared to male counterparts as testosterone may reduce ABCC2 protein expression (Rost et al, 2005;Suzuki et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…Studies have shown that expression of ABCC2 protein was 1.5 fold higher in female rat hepatocytes compared to male counterparts as testosterone may reduce ABCC2 protein expression (Rost et al, 2005;Suzuki et al, 2006). On the other hand, expression of ABCC2 protein in renal cells was significantly higher in males as compared to females (Wang et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Influence of gender on ABCC2 expression in peripheral blood mononuclear cells

Sudchada¹,

Chareanchim²,

Assawamakin³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. It is known that several factors, including gender, may influence the expression of multidrug resistance associated proteins 2 (MRP2/ABCC2) in the peripheral blood mononuclear cells (PBMCs). This study aims to compare ABCC2 gene expression in PBMCs of healthy males and females. PBMCs were extracted from 48 females and 44 males, and gene expression was measured using real-time quantitative polymerase chain reaction (real-time QPCR). Multiple housekeeping genes (Actin-β, β2-M, GAPDH) were utilized as endogenous controls. The stability of housekeeping genes was verified using the Excel-based Bestkeeper ® program. Our results showed that expression level of ABCC2 in PBMCs was 1.2-1.4 fold higher in males compared to that in females, depending on the endogenous control(s) used. However, this difference was not statistically significant. When considering using a single endogenous control gene, GAPDH and Actin-β were found to be more suitable than β2-M. Moreover, GAPDH + Actin-β, or the combination of all three housekeeping gene as endogenous control(s) showed greater stability than other endogenous control genes for normalization of ABCC2 expression in PBMCs. This study suggests that ABCC2 expression in PBMCs may be, in part, influenced by gender, and that at least two endogenous control genes should be utilized for gene expression normalization.

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Section: Comparing Levels Of Abcc2 Expression Between Males and Femalessupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Influence of gender on ABCC2 expression in peripheral blood mononuclear cells

Sudchada¹,

Chareanchim²,

Assawamakin³

et al. 2015

Genet. Mol. Res.

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“…Patients at dose level III presented significant changes in some PK parameters of PLD that cannot be associated with the administration of the other two drugs since that effect appeared on PLD-monotherapy day (first day of the cycle) and before PCX and GEM administration (PLD t max for dose level III: 3 h). Studies on gender-dependent differences of doxorubicin have already been reported (Clements et al, 2002;Suzuki et al, 2006). In the present study, five out of six patients at dose level III were females implying that gender-related effects could be the most possible explanation for the observed differences in the PK parameters of PLD.…”

Section: Discussionsupporting

confidence: 51%

A dose escalation and pharmacokinetic study of biweekly pegylated liposomal doxorubicin, paclitaxel and gemcitabine in patients with advanced solid tumours

et al. 2007

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To determine the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of pegylated liposomal doxorubicin (PLD), paclitaxel (PCX) and gemcitabine (GEM) combination administered biweekly in patients with advanced solid tumours. Twenty-two patients with advanced-stage solid tumours were treated with escalated doses of PLD on day 1 and PCX plus GEM on day 2 (starting doses: 10, 100 and 800 mg m À2 , respectively) every 2 weeks. DLTs and pharmacokinetic (PK) parameters of all drugs were determined during the first cycle of treatment. All but six (73%) patients had previously received at least one chemotherapy regimen. The DLT dose level was reached at PLD 12 mg m À2 , PCX 110 mg m À2 and GEM 1000 mg m À2 with neutropaenia being the doselimiting event. Of the 86 chemotherapy cycles delivered, grade 3 and 4 neutropaenia occurred in 20% with no cases of febrile neutropaenia. Non-haematological toxicities were mild. The recommended MTDs are PLD 12 mg m À2 , PCX 100 mg m À2 and GEM 1000 mg m À2 administered every 2 weeks. The PK data revealed no obvious drug interactions. Biweekly administration of PLD, PCX and GEM is a well-tolerated chemotherapy regimen, which merits further evaluation in various types of solid tumours.

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“…ABCB1 geni, hormonal tetiklemeye karşı oldukça duyarlıdır (116). Dolaşımdaki cinsiyet hormonları sistemik organlardaki P-gp ekspresyonu ve fonksiyonunu etkileyerek cinsiyete bağlı ilaç cevabında farklılıklara neden olabilmektedir (117,118). Karaciğerde P-gp ekspresyonunun cinsiyetler arası farklılığın gösterilmesi ile özellikle bağırsak lümeni gibi P-gp'nin olduğu diğer dokularda da bu farklılığın olup olmadığı incelenmiştir (97,119).…”

Section: Abc Taşıyıcı Proteinlerinin Ekspresyonunda Cinsiyete Bağlı Funclassified