The objective of this proof-of-concept study was to conduct a series of tests to the hypothesis that Midazolam ( MDZ)  is efficacious for treatment of acute Hydrogen sulfide ( H 2 S) -induced mortality and neurotoxicity . This is a groundbreaking study because no prior studies have addressed this question.

Hydrogen sulfide ( H 2 S ) is an extremely toxic gas and is only second to carbon monoxide as a leading cause of gas-induced deaths . It is a hazard in many occupational settings where accidental acute high-exposure exposure may occur following industrial malfunction or because of nefarious acts. 

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, researchers 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.

All animal studies were approved by the Iowa State University Institutional Animal Care and Use Committee (IACUC). The 7–8-week-old C57/BL6 male mice used in these studies were purchased from The Jackson Laboratories (Bar Harbor, ME) and weighed 20–25 g at the beginning of the experiment.

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 if 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, the study findings showed that MDZ is a promising drug for reducing H 2 S-induced acute mortality, neurotoxicity, and neurological sequelae.