Details

Autor(en) / Beteiligte

• Anantharam, Poojya
• Kim, Dong-Suk
• Whitley, Elizabeth M.
• Mahama, Belinda
• Imerman, Paula
• Padhi, Piyush
• Rumbeiha, Wilson K.

Titel

Midazolam Efficacy Against Acute Hydrogen Sulfide-Induced Mortality and Neurotoxicity

Ist Teil von

• Journal of medical toxicology, 2018-03, Vol.14 (1), p.79-90

Ort / Verlag

New York: Springer US

Erscheinungsjahr

2018

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Hydrogen sulfide (H 2 S) 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 H 2 S exposure causes death, while survivors may develop neurological sequelae. Currently, there is no suitable antidote for treatment of acute H 2 S-induced neurotoxicity. Midazolam (MDZ), an anti-convulsant drug recommended for treatment of nerve agent intoxications, could also be of value in treating acute H 2 S intoxication. In this study, we tested the hypothesis that MDZ is effective in preventing/treating acute H 2 S-induced neurotoxicity. This proof-of-concept study had two objectives: to determine whether MDZ prevents/reduces H 2 S-induced mortality and to test whether MDZ prevents H 2 S-induced neurological sequelae. MDZ (4 mg/kg) was administered IM in mice, 5 min pre-exposure to a high concentration of H 2 S at 1000 ppm or 12 min post-exposure to 1000 ppm H 2 S followed by 30 min 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 H 2 S-induced lethality, seizures, knockdown, and behavioral deficits ( p  < 0.01). MDZ also significantly prevented H 2 S-induced neurological sequelae, including weight loss, behavior deficits, neuroinflammation, and histopathologic lesions ( p  < 0.01). Overall, our findings show that MDZ is a promising drug for reducing H 2 S-induced acute mortality, neurotoxicity, and neurological sequelae.