, Volume 24, Issue 4, pp 615–628

Interactive effect of arsenic and fluoride on cardio-respiratory disorders in male rats: possible role of reactive oxygen species

  • S. J. S. Flora
  • Vidhu Pachauri
  • Megha Mittal
  • Deo Kumar

DOI: 10.1007/s10534-011-9412-y

Cite this article as:
Flora, S.J.S., Pachauri, V., Mittal, M. et al. Biometals (2011) 24: 615. doi:10.1007/s10534-011-9412-y


Epidemiological evidence demonstrates positive correlation between environmental and occupational arsenic or fluoride exposure and risk to various cardio-respiratory disorders. Arsenic-exposure has been associated with atherosclerosis, hypertension, cerebrovascular diseases, ischemic heart disease, and peripheral vascular disorders, whereas Fluoride-exposure manifests cardiac irregularities and low blood pressure (BP). Present study aims to study the combined effects of these toxicants on various cardio-respiratory variables in male rats. Single intravenous (i.v.) dose of arsenic (1, 5, 10 mg/kg) or fluoride (5, 10, 20, 36.5 mg/kg) either alone or in combination were administered. Individual exposure to arsenic or fluoride led to a significant depletion of mean arterial pressure, heart rate (HR), respiration rate and neuromuscular (NM) transmission in a dose-dependent manner. These changes were accompanied by increased levels of blood reactive oxygen species (ROS) and decreased glutathione (GSH) concentrations. An increase in the blood acetyl cholinesterase (AChE) activity was observed in both arsenic or fluoride exposed rats. These changes were significantly more pronounced in arsenic-exposed animals than in fluoride. During combined exposure to arsenic (5 mg/kg) + fluoride (20 mg/kg) or arsenic (10 mg/kg) + fluoride (36.5 mg/kg) the toxic effects were more pronounced compared to individual toxicities of arsenic or fluoride alone. However, combined exposure to arsenic (5 mg/kg) + fluoride (36.5 mg/kg) resulted in antagonistic effects on variables suggestive of altered cardio-respiratory function and oxidative stress. The results from the present study suggest that arsenic or fluoride individually demonstrate cardio-respiratory failure at all doses whereas during combination exposure these toxins show variable toxicities; both synergistic and antagonistic effects depending upon the dose. Moreover, it may be concluded that arsenic and/or fluoride cardio-respiratory toxicity may be mediated via oxidative stress. However, these results are new in the discipline thus requires further exploration.


Cardio-respiration Oxidative stress Neuromuscular transmission Heart rate Respiration rate Arterial pressure Arsenic Fluoride 









Reactive oxygen species


Reduced glutathione


Acetyl cholinesterase


Systolic BP


Mean arterial pressure

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • S. J. S. Flora
    • 1
  • Vidhu Pachauri
    • 1
  • Megha Mittal
    • 1
  • Deo Kumar
    • 1
  1. 1.Division of Pharmacology and ToxicologyDefence Research and Development EstablishmentGwaliorIndia

Personalised recommendations