Baclofen systemic toxicity: Experimental histopathological and biochemical study

Hum Exp Toxicol. 2018 Apr;37(4):431-441. doi: 10.1177/0960327117712369. Epub 2017 May 31.

Abstract

Objective: The present study was designed to highlight the toxic impact of baclofen on both biochemical and histopathological aspects in rats' liver, gastric, lung, kidney, and brain tissues.

Methods: The study was performed on 30 healthy adult male albino rats divided into four groups with 5 rats in each control group, and 10 rats in either experimental groups (two experimental and two control groups). Five rats (negative control) were kept in a quite non-stressful environment, provided with food ad libitum and free access to water. Normal saline (1 ml) was given orally as placebo in the positive control group ( n = 5). Experimental group III, baclofen acute toxicity group (10 rats): Each animal received a single dose of lethal dose (LD50) of baclofen orally by gavage. It equals 145 mg/kg body weight. The rats were observed for acute toxicity manifestations as well as for LD50 deaths. Group IV, (baclofen-dependent group, 10 rats): Each animal received baclofen (1/10th LD50) in gradually increasing doses for 1 month.

Results: The levels of blood urea nitrogen, creatinine kinase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, cardiac troponin I, and prothrombin time in both baclofen-treated groups showed significant elevation when compared to controls. There were brain, lung, gastric, hepatic, and renal histopathological changes in baclofen-treated rats whose severity varied between the two experimental groups.

Conclusion and recommendation: Baclofen toxicity is an under diagnosed emergency. Physicians should consider baclofen toxicity in users having hepatorenal dysfunction, presenting with altered mental status, bradycardia, and hypotension.

Keywords: Baclofen; biochemical; brain; gastric; hepatic; histopathology; lung; renal; toxicity.

MeSH terms

  • Animals
  • Baclofen / toxicity*
  • Biomarkers / blood
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • GABA-B Receptor Agonists / toxicity*
  • Gastric Mucosa / metabolism
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Lethal Dose 50
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Rats
  • Stomach / drug effects*
  • Stomach / pathology
  • Time Factors

Substances

  • Biomarkers
  • GABA-B Receptor Agonists
  • Baclofen