» Articles » PMID: 29217817

Acetazolamide Suppresses Multi-Drug Resistance-Related Protein 1 and P-Glycoprotein Expression by Inhibiting Aquaporins Expression in a Mesial Temporal Epilepsy Rat Model

Overview
Journal Med Sci Monit
Date 2017 Dec 9
PMID 29217817
Citations 8
Authors
Affiliations
Soon will be listed here.
Abstract

BACKGROUND Mesial temporal epilepsy (MTLE) is the most common type of focal epilepsy in adults, and is often drug-resistant. This study investigated the effects of aquaporins (AQP) inhibitor on multi-drug-resistant protein expression in an MTLE rat model. MATERIAL AND METHODS The MTLE rat model was established by injecting pilocarpine into rats. The MTLE rats were divided into an MTLE-6 h group, an MTLE-12 h group, and an MTLE-24 h group, together with a normal saline group (NS), to examine the AQP4 expression by using Western blot assay and immunohistochemistry assay. The other 18 MTLE model rats were used to observe the effects of the AQP4 inhibitor, acetazolamide, on the multi-drug-resistant protein 1 (MRP1) and P-glycoprotein (Pgp) by using Western blot and immunohistochemistry assays, respectively. RESULTS AQP4 expression was enhanced in hippocampal tissues of MTLE model rats compared to NS rats (P<0.05). More positively stained AQP4 was discovered in hippocampal tissues of MTLE model rats. AQP4 inhibitor significantly decreased multi-drug-resistant protein MRP1 and Pgp expression in the AQP4 inhibitor Interfere group and the AQP4 inhibitor Therapy group compared to the TMLE model group (P<0.05). CONCLUSIONS The present findings confirm that the AQP4 inhibitor, acetazolamide, effectively inhibits the multi-drug-resistant protein, MRP1, and Pgp, in the MTLE rat model.

Citing Articles

Non-coding RNAs and Aquaporin 4: Their Role in the Pathogenesis of Neurological Disorders.

Yaghoobi Z, Seyed Bagher Nazeri S, Asadi A, Derafsh E, Taheri A, Tamtaji Z Neurochem Res. 2023; 49(3):583-596.

PMID: 38114727 DOI: 10.1007/s11064-023-04067-8.


The Role of Aquaporins in Epileptogenesis-A Systematic Review.

Bonosi L, Benigno U, Musso S, Giardina K, Gerardi R, Brunasso L Int J Mol Sci. 2023; 24(15).

PMID: 37569297 PMC: 10418736. DOI: 10.3390/ijms241511923.


Converging Mechanisms of Epileptogenesis and Their Insight in Glioblastoma.

Hills K, Kostarelos K, Wykes R Front Mol Neurosci. 2022; 15:903115.

PMID: 35832394 PMC: 9271928. DOI: 10.3389/fnmol.2022.903115.


ATP-binding cassette (ABC) drug transporters in the developing blood-brain barrier: role in fetal brain protection.

Eng M, Imperio G, Bloise E, Matthews S Cell Mol Life Sci. 2022; 79(8):415.

PMID: 35821142 PMC: 11071850. DOI: 10.1007/s00018-022-04432-w.


The complex relationship between multiple drug resistance and the tumor pH gradient: a review.

Koltai T Cancer Drug Resist. 2022; 5(2):277-303.

PMID: 35800371 PMC: 9255250. DOI: 10.20517/cdr.2021.134.


References
1.
Jin H, Li W, Dong C, Ma L, Wu J, Zhao W . Effects of Different Doses of Levetiracetam on Aquaporin 4 Expression in Rats with Brain Edema Following Fluid Percussion Injury. Med Sci Monit. 2016; 22:678-86. PMC: 4774575. DOI: 10.12659/msm.897201. View

2.
van der Deen M, Marks H, Willemse B, Postma D, Muller M, Smit E . Diminished expression of multidrug resistance-associated protein 1 (MRP1) in bronchial epithelium of COPD patients. Virchows Arch. 2006; 449(6):682-8. DOI: 10.1007/s00428-006-0240-3. View

3.
Tanimura Y, Hiroaki Y, Fujiyoshi Y . Acetazolamide reversibly inhibits water conduction by aquaporin-4. J Struct Biol. 2008; 166(1):16-21. DOI: 10.1016/j.jsb.2008.11.010. View

4.
Dombrowski S, Desai S, Marroni M, Cucullo L, Goodrich K, Bingaman W . Overexpression of multiple drug resistance genes in endothelial cells from patients with refractory epilepsy. Epilepsia. 2002; 42(12):1501-6. DOI: 10.1046/j.1528-1157.2001.12301.x. View

5.
Umschweif G, Alexandrovich A, Trembovler V, Horowitz M, Shohami E . Hypoxia-inducible factor 1 is essential for spontaneous recovery from traumatic brain injury and is a key mediator of heat acclimation induced neuroprotection. J Cereb Blood Flow Metab. 2013; 33(4):524-31. PMC: 3618386. DOI: 10.1038/jcbfm.2012.193. View