Abstract
An: 2015, Nr.1, Articol Nr. 2
Title: 

ASSESSMENT OF DANTROLENE TOXICITY IN INTRAVENOUS LONG TERM ADMINISTRATION

Authors: 

      R.C. Tudor, Cristina Amihaesei, Carmen Lăcrămioara Zamfir - “Gr.T. Popa” University of Medicine and Pharmacy Iaşi, Department of Morpho-Functional Sciences, Discipline of Histology
      Roxana Folescu - “V. Babeş” University of Medicine and Pharmacy, Timisoara, Department of Anatomy
      C.I. Stan - “Gr.T. Popa” University of Medicine and Pharmacy Iaşi, Department of Morpho-Functional Sciences, Discipline of Anatomy
      ASSESSMENT OF INTRAVENOUS DANTROLENE TOXICITY IN LONG TERM ADMINISTRATION (Abstract): Dantrolene represents a direct acting skeletal muscle relaxant, used for the treatment of spasticity as a result of spinal cord or cerebrum injuries, stroke, multiple sclerosis, cerebrovascular accident, but also in the prophylaxis and therapy of the malignant hyperthermia. Accumulated data sustain that we have to regard hepatotoxicity as the major concern of dantrolene, but there are also opinions suggesting a variable degree of renal injury, which can compromite the renal functions. Usually, mannitol is added to dantrolene in order to determine the isotonicity of the solution when intravenous administered and its side effects can be considerable. The aim of our study is to determine the occurrence and the extent of the hepatic and renal injuries produced by intravenous long term dantrolene administration, for a further design of a new type of dantrolene incorporated microparticles. Material and methods: Wistar adult female rats were randomly distributed in two groups: control group and dantrolene administered group, for four weeks. Dantrolene was given in intraperitoneal daily administration for the second group. At the end of the experiment, the hepatic and renal tissues were prelevated from each group and specifically treated for the histopathologic exam. Results: hepatic steatosis and incipient hepatitis were present in all the animals from the second group; the renal lesions (especially renal tubular damages), were also present, but inconsistent as frequency. Conclusions: hepatotoxicity of dantrolene remains the major inconvenient of the its therapeutic use; the renal injuries, where they are manifest, require a better approach, suggesting that supportive adjuvants have to be added.
Key words: DANTROLENE, SKELETAL MUSCLE, MANNITOL, STEATOSIS, RENAL TUBULAR DAMAGES
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