The Effects of Cetirizine on P-glycoprotein Expression and Function In vitro and In situ

Abbasi, Mehran Mesgari; Valizadeh, Hadi; Hamishekar, Hamed; Mohammadnejad, Leila; Zakeri–Milani, Parvin

doi:10.15171/apb.2016.017

Cited by 13 publications

(8 citation statements)

References 22 publications

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“…Most antihistamines are ABCB1 substrates, but some antihistamine classes are ABCB1 inhibitors. For example, cetirizine downregulates ABCB1 in vitro [ 50 ]. Similarly, terfenadine demonstrated strong inhibitory effects on ABCB1 in vitro [ 51 ].…”

Section: Systemic Agentsmentioning

confidence: 99%

ABCB1 in dermatology: roles in skin diseases and their treatment

Weng

Tsai

2021

J Mol Med

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Adenosine triphosphate–binding cassette subfamily B member 1 (ABCB1), also known as permeability glycoprotein, multidrug-resistant protein 1, or cluster of differentiation 243 (CD243), is a crucial protein for purging foreign substances from cells. The functions of ABCB1 have been investigated extensively for their roles in cancer, stem cells, and drug resistance. Abundant pharmacogenetic studies have been conducted on ABCB1 and its association with treatment responsiveness to various agents, particularly chemotherapeutic and immunomodulatory agents. However, its functions in the skin and implications on dermatotherapeutics are far less reported. In this article, we reviewed the roles of ABCB1 in dermatology. ABCB1 is expressed in the skin and its appendages during drug delivery and transport. It is associated with treatment responsiveness to various agents, including topical steroids, methotrexate, cyclosporine, azathioprine, antihistamines, antifungal agents, colchicine, tacrolimus, ivermectin, tetracycline, retinoid acids, and biologic agents. Moreover, genetic variation in ABCB1 is associated with the pathogenesis of several dermatoses, including psoriasis, atopic dermatitis, melanoma, bullous pemphigoid, Behçet disease, and lichen planus. Further investigation is warranted to elucidate the roles of ABCB1 in dermatology and the possibility of enhancing therapeutic efficacy through ABCB1 manipulation.

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Section: Systemic Agentsmentioning

confidence: 99%

ABCB1 in dermatology: roles in skin diseases and their treatment

Weng

Tsai

2021

J Mol Med

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“…On the other hand, IP6 induced a significant decrease in P-gp expression in rat intestinal segments (Figure B,C), Caco-2 cells (Figure A,B), and MDCK II-MDR1 cells (Figure B,C) at 2 h. These results suggest that the inhibitory effects of IP6 on P-gp efflux are likely the result of the effects of IP6 on protein expression. Similarly, it was speculated that cetirizine and disodium ascorbyl phytostanol (DAPP) also decreased P-gp-mediated drug efflux via the down-regulation of P-gp gene and protein expression. , Interestingly, an increase in P-gp mRNA levels contradicts the observed P-gp protein level decreases (Figure C), and P-gp protein expression remain unchanged with increasing concentrations of IP6 when pretreated with cyclohexamide (an inhibitor of translation) (data not shown), suggesting that IP6 might arrest the P-gp translation process to down-regulate the P-gp expression. Meanwhile, IP6 likely activated P-gp proteins or other substances, such as steroid xenobiotic receptors, which subsequently resulted in feedback regulation of P-gp mRNA.…”

Section: Discussionmentioning

confidence: 95%

Inhibition of P-Glycoprotein Mediated Efflux in Caco-2 Cells by Phytic Acid

Xia

et al. 2018

J. Agric. Food Chem.

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Phytic acid (IP6) is a natural phosphorylated inositol, which is abundantly present in most cereal grains and seeds. This study investigated the effects of IP6 regulation on P-glycoprotein (P-gp) and its potential mechanisms using in situ and in vitro models. The effective permeability of the typical P-gp substrate rhodamine 123 (R123) in colon was significantly increased from (1.69 ± 0.22) × 10 cm/s in the control group to (3.39 ± 0.417) × 10 cm/s (p < 0.01) in the 3.5 mM IP6 group. Additionally, IP6 can concentration-dependently decrease the R123 efflux ratio in both Caco-2 and MDCK II-MDR1 cell monolayers and increase intracellular R123 accumulation in Caco-2 cells. Furthermore, IP6 noncompetitively inhibited P-gp by impacting R123 efflux kinetics. The noncompetitive inhibition of P-gp by IP6 was likely due to decreases in P-gp ATPase activity and P-gp molecular conformational changes induced by IP6. In summary, IP6 is a promising P-gp inhibitor candidate.

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“…This means that morphine could produce a better analgesic activity in the individuals with the lower expression of P-gp transporter. More recently, Mesgari Abbasi et al (2016) reported that cetirizine has a P-gp inhibitory activity [35]. The inhibition of P-gp by cetirizine may be one of the reasons that cause enhancement of morphine-induced analgesia in the combination therapy.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Histamine H1 Receptor Antagonists on the Morphine-Induced Antinociception in the Acute Trigeminal Model of Nociception in Rats

Khalilzadeh

Azarpey

Hazrati

2016

Asian J Pharm Clin Res

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Objective: In this study, the effect of different classes of histamine H 1 receptor antagonists (chlorpheniramine, cetirizine, and fexofenadine), µ opioid receptor agonist (morphine), and opioid receptor antagonist (naloxone) in separate and combined treatments were investigated on the acute trigeminal model of pain in rats.Methods: Eye wiping test used for induction of acute trigeminal pain by putting a drop of NaCl, 5 M solution (40 µl) on the corneal surface of the eye, and the number of eye wipes counted during the first 30 seconds.Results: Intraperitoneal injection of both chlorpheniramine and cetirizine at doses of 10 and 20 mg/kg significantly inhibited the acute trigeminal pain. However, fexofenadine did not change corneal pain response. Morphine at doses of 1.25, 2.5, and 5 mg/kg reduced eye wipe responses. Administration of both chlorpheniramine and cetirizine but not fexofenadine before morphine-enhanced morphine analgesic activity, also pretreatment of animals with naloxone inhibited morphine, chlorpheniramine, and cetirizine-induced analgesia in the acute corneal pain. Conclusion:Our results showed that chlorpheniramine as a histamine H 1 antagonist that efficiently Penetrates blood-brain barrier (BBB) and cetirizine with less penetration of BBB but not fexofenadine (an H 1 receptor antagonist with a negligible brain-accessibility) could induce analgesia in the acute corneal pain via opioidergic mechanism. Coadministration of morphine with chlorpheniramine or cetirizine could enhance its analgesic activity in the acute trigeminal model of pain in rats.

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The Effects of Cetirizine on P-glycoprotein Expression and Function In vitro and In situ

Cited by 13 publications

References 22 publications

ABCB1 in dermatology: roles in skin diseases and their treatment

ABCB1 in dermatology: roles in skin diseases and their treatment

Inhibition of P-Glycoprotein Mediated Efflux in Caco-2 Cells by Phytic Acid

The Effect of Histamine H1 Receptor Antagonists on the Morphine-Induced Antinociception in the Acute Trigeminal Model of Nociception in Rats

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