Acetazolamide prevents vacuolar myopathy in skeletal muscle of K +-depleted rats

D. Tricarico, S. Lovaglio, A. Mele, G. Rotondo, E. Mancinelli, G. Meola, D. C. Camerino

Research output: Contribution to journalArticle

Abstract

Background and purpose: Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP). Whether these drugs prevent vacuolar myopathy, which is a pathogenic factor in hypoPP, is unknown. The effects of these drugs on the efflux of lactate from skeletal muscle were also investigated. Experimental approach: For 10 days, K +-depleted rats, a model of hypoPP, were administered 5.6 mg kg -1 day -1 of acetazolamide, dichlorphenamide or bendroflumethiazide (the last is not an inhibitor of CA). Histological analysis of vacuolar myopathy and in vitro lactate efflux measurements were performed in skeletal muscles from treated and untreated K +-depleted rats, and also from normokalemic rats. Key results: About three times as many vacuoles were found in the type II fibres of tibialis anterioris muscle sections from K +-depleted rats as were found in the same muscle from normokalemic rats. In ex vivo experiments, a higher efflux of lactate on in vitro incubation was found in muscles of K +-depleted rats compared with that found in muscles from normokalemic rats. After treatment of K +-depleted rats with acetazolamide, the numbers of vacuoles in tibialis anterioris muscle decreased to near normal values. Incubation with acetazolamide in vitro inhibited efflux of lactate from muscles of K +-depleted rats. In contrast, bendroflumethiazide and dichlorphenamide failed to prevent vacuolar myopathy after treatment in vivo and failed to inhibit lactate efflux in vitro. Conclusions and implications: Acetazolamide prevents vacuolar myopathy in K +-depleted rats. This effect was associated with inhibition of lactate transport, rather than inhibition of CA.

Original languageEnglish
Pages (from-to)183-190
Number of pages8
JournalBritish Journal of Pharmacology
Volume154
Issue number1
DOIs
Publication statusPublished - May 2008

Fingerprint

Acetazolamide
Skeletal Muscle
Dichlorphenamide
Lactic Acid
Hypokalemic Periodic Paralysis
Muscles
Bendroflumethiazide
Carbonic Anhydrase Inhibitors
Vacuoles
Vacuolar myopathy
Carbonic Anhydrases
Pharmaceutical Preparations
Reference Values

Keywords

  • Carbonic anhydrase inhibitors
  • Histopathology
  • K -depleted rats
  • Lactate efflux
  • Periodic paralysis
  • Vacuolar myopathy

ASJC Scopus subject areas

  • Pharmacology

Cite this

Tricarico, D., Lovaglio, S., Mele, A., Rotondo, G., Mancinelli, E., Meola, G., & Camerino, D. C. (2008). Acetazolamide prevents vacuolar myopathy in skeletal muscle of K +-depleted rats. British Journal of Pharmacology, 154(1), 183-190. https://doi.org/10.1038/bjp.2008.42

Acetazolamide prevents vacuolar myopathy in skeletal muscle of K +-depleted rats. / Tricarico, D.; Lovaglio, S.; Mele, A.; Rotondo, G.; Mancinelli, E.; Meola, G.; Camerino, D. C.

In: British Journal of Pharmacology, Vol. 154, No. 1, 05.2008, p. 183-190.

Research output: Contribution to journalArticle

Tricarico, D, Lovaglio, S, Mele, A, Rotondo, G, Mancinelli, E, Meola, G & Camerino, DC 2008, 'Acetazolamide prevents vacuolar myopathy in skeletal muscle of K +-depleted rats', British Journal of Pharmacology, vol. 154, no. 1, pp. 183-190. https://doi.org/10.1038/bjp.2008.42
Tricarico, D. ; Lovaglio, S. ; Mele, A. ; Rotondo, G. ; Mancinelli, E. ; Meola, G. ; Camerino, D. C. / Acetazolamide prevents vacuolar myopathy in skeletal muscle of K +-depleted rats. In: British Journal of Pharmacology. 2008 ; Vol. 154, No. 1. pp. 183-190.
@article{13b846165f4848fc886e2ca5a7d92f04,
title = "Acetazolamide prevents vacuolar myopathy in skeletal muscle of K +-depleted rats",
abstract = "Background and purpose: Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP). Whether these drugs prevent vacuolar myopathy, which is a pathogenic factor in hypoPP, is unknown. The effects of these drugs on the efflux of lactate from skeletal muscle were also investigated. Experimental approach: For 10 days, K +-depleted rats, a model of hypoPP, were administered 5.6 mg kg -1 day -1 of acetazolamide, dichlorphenamide or bendroflumethiazide (the last is not an inhibitor of CA). Histological analysis of vacuolar myopathy and in vitro lactate efflux measurements were performed in skeletal muscles from treated and untreated K +-depleted rats, and also from normokalemic rats. Key results: About three times as many vacuoles were found in the type II fibres of tibialis anterioris muscle sections from K +-depleted rats as were found in the same muscle from normokalemic rats. In ex vivo experiments, a higher efflux of lactate on in vitro incubation was found in muscles of K +-depleted rats compared with that found in muscles from normokalemic rats. After treatment of K +-depleted rats with acetazolamide, the numbers of vacuoles in tibialis anterioris muscle decreased to near normal values. Incubation with acetazolamide in vitro inhibited efflux of lactate from muscles of K +-depleted rats. In contrast, bendroflumethiazide and dichlorphenamide failed to prevent vacuolar myopathy after treatment in vivo and failed to inhibit lactate efflux in vitro. Conclusions and implications: Acetazolamide prevents vacuolar myopathy in K +-depleted rats. This effect was associated with inhibition of lactate transport, rather than inhibition of CA.",
keywords = "Carbonic anhydrase inhibitors, Histopathology, K -depleted rats, Lactate efflux, Periodic paralysis, Vacuolar myopathy",
author = "D. Tricarico and S. Lovaglio and A. Mele and G. Rotondo and E. Mancinelli and G. Meola and Camerino, {D. C.}",
year = "2008",
month = "5",
doi = "10.1038/bjp.2008.42",
language = "English",
volume = "154",
pages = "183--190",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Acetazolamide prevents vacuolar myopathy in skeletal muscle of K +-depleted rats

AU - Tricarico, D.

AU - Lovaglio, S.

AU - Mele, A.

AU - Rotondo, G.

AU - Mancinelli, E.

AU - Meola, G.

AU - Camerino, D. C.

PY - 2008/5

Y1 - 2008/5

N2 - Background and purpose: Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP). Whether these drugs prevent vacuolar myopathy, which is a pathogenic factor in hypoPP, is unknown. The effects of these drugs on the efflux of lactate from skeletal muscle were also investigated. Experimental approach: For 10 days, K +-depleted rats, a model of hypoPP, were administered 5.6 mg kg -1 day -1 of acetazolamide, dichlorphenamide or bendroflumethiazide (the last is not an inhibitor of CA). Histological analysis of vacuolar myopathy and in vitro lactate efflux measurements were performed in skeletal muscles from treated and untreated K +-depleted rats, and also from normokalemic rats. Key results: About three times as many vacuoles were found in the type II fibres of tibialis anterioris muscle sections from K +-depleted rats as were found in the same muscle from normokalemic rats. In ex vivo experiments, a higher efflux of lactate on in vitro incubation was found in muscles of K +-depleted rats compared with that found in muscles from normokalemic rats. After treatment of K +-depleted rats with acetazolamide, the numbers of vacuoles in tibialis anterioris muscle decreased to near normal values. Incubation with acetazolamide in vitro inhibited efflux of lactate from muscles of K +-depleted rats. In contrast, bendroflumethiazide and dichlorphenamide failed to prevent vacuolar myopathy after treatment in vivo and failed to inhibit lactate efflux in vitro. Conclusions and implications: Acetazolamide prevents vacuolar myopathy in K +-depleted rats. This effect was associated with inhibition of lactate transport, rather than inhibition of CA.

AB - Background and purpose: Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP). Whether these drugs prevent vacuolar myopathy, which is a pathogenic factor in hypoPP, is unknown. The effects of these drugs on the efflux of lactate from skeletal muscle were also investigated. Experimental approach: For 10 days, K +-depleted rats, a model of hypoPP, were administered 5.6 mg kg -1 day -1 of acetazolamide, dichlorphenamide or bendroflumethiazide (the last is not an inhibitor of CA). Histological analysis of vacuolar myopathy and in vitro lactate efflux measurements were performed in skeletal muscles from treated and untreated K +-depleted rats, and also from normokalemic rats. Key results: About three times as many vacuoles were found in the type II fibres of tibialis anterioris muscle sections from K +-depleted rats as were found in the same muscle from normokalemic rats. In ex vivo experiments, a higher efflux of lactate on in vitro incubation was found in muscles of K +-depleted rats compared with that found in muscles from normokalemic rats. After treatment of K +-depleted rats with acetazolamide, the numbers of vacuoles in tibialis anterioris muscle decreased to near normal values. Incubation with acetazolamide in vitro inhibited efflux of lactate from muscles of K +-depleted rats. In contrast, bendroflumethiazide and dichlorphenamide failed to prevent vacuolar myopathy after treatment in vivo and failed to inhibit lactate efflux in vitro. Conclusions and implications: Acetazolamide prevents vacuolar myopathy in K +-depleted rats. This effect was associated with inhibition of lactate transport, rather than inhibition of CA.

KW - Carbonic anhydrase inhibitors

KW - Histopathology

KW - K -depleted rats

KW - Lactate efflux

KW - Periodic paralysis

KW - Vacuolar myopathy

UR - http://www.scopus.com/inward/record.url?scp=42949089844&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42949089844&partnerID=8YFLogxK

U2 - 10.1038/bjp.2008.42

DO - 10.1038/bjp.2008.42

M3 - Article

C2 - 18345024

AN - SCOPUS:42949089844

VL - 154

SP - 183

EP - 190

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 1

ER -