Midazolam Efficacy Against Acute Hydrogen Sulfide-Induced Mortality and Neurotoxicity

Autor: Piyush Padhi, Belinda Mahama, Dong Suk Kim, Paula M. Imerman, Poojya Anantharam, Elizabeth M. Whitley, Wilson K. Rumbeiha
Rok vydání: 2017
Předmět:
Male
Translational model
Health
Toxicology and Mutagenesis
medicine.medical_treatment
Toxicology
Inbred C57BL
Mice
0302 clinical medicine
Weight loss
Hydrogen Sulfide
Antidote
media_common
Nerve agent
Hydrogen sulfide
Behavior
Animal
Poisoning
Brain
Pharmacology and Pharmaceutical Sciences
5.1 Pharmaceuticals
Anesthesia
Neurotoxicity Syndromes
medicine.symptom
Development of treatments and therapeutic interventions
medicine.drug
Drug
media_common.quotation_subject
Midazolam
Clinical Sciences
Vaccine Related
03 medical and health sciences
Biodefense
Behavioral and Social Science
medicine
Neurotoxicity
Animals
Neurodegeneration
GABA Modulators
Neuroinflammation
Behavior
Acute toxicity
business.industry
Animal
Prevention
Neurosciences
030208 emergency & critical care medicine
medicine.disease
equipment and supplies
Brain Disorders
Mice
Inbred C57BL
business
030217 neurology & neurosurgery
Zdroj: Journal of medical toxicology : official journal of the American College of Medical Toxicology, vol 14, iss 1
ISSN: 1937-6995
Popis: Hydrogen sulfide (H2S) is a colorless, highly neurotoxic gas. It is not only an occupational and environmental hazard but also of concern to the Department of Homeland Security for potential nefarious use. Acute high-dose H2S exposure causes death, while survivors may develop neurological sequelae. Currently, there is no suitable antidote for treatment of acute H2S-induced neurotoxicity. Midazolam (MDZ), an anti-convulsant drug recommended for treatment of nerve agent intoxications, could also be of value in treating acute H2S intoxication. In this study, we tested the hypothesis that MDZ is effective in preventing/treating acute H2S-induced neurotoxicity. This proof-of-concept study had two objectives: to determine whether MDZ prevents/reduces H2S-induced mortality and to test whether MDZ prevents H2S-induced neurological sequelae. MDZ (4mg/kg) was administered IM in mice, 5min pre-exposure to a high concentration of H2S at 1000ppm or 12min post-exposure to 1000ppm H2S followed by 30min of continuous exposure. A separate experiment tested whether MDZ pre-treatment prevented neurological sequelae. Endpoints monitored included assessment of clinical signs, mortality, behavioral changes, and brain histopathological changes. MDZ significantly reduced H2S-induced lethality, seizures, knockdown, and behavioral deficits (p 
Databáze: OpenAIRE
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