Table 3.

Studies of molecular hydrogen against sepsis through an anti-apoptosis effect

Drug	Authors	Animal/cell	Disease model	Administration	Effects	Signaling pathways
HRS	Sun et. al 201121	C57BL/6 mice	Septic liver injury (GalN/LPS)	HRS 8ml/kg/3h × 3 i.p.	TUNEL (+)↓, caspase-3 ↓, cPARP ↓	ROS-JNK-Caspase3 ↓
2% H2	Qiu et. al 201113	C57BL/6 mice	Septic lung injury (LPS)	2% H2 inhalation	TUNEL (+) ↓, Bax ↓, caspase-3↓, Bcl-xl ↑	ROS-JNK-Caspase3 ↓
HRS 2% H2	Xie et. al 20128	C57BL/6 mice	Septic lung injury (LPS)	2% H2 inhalation/HRS 10 ml/kg i.p.	TUNEL (+) ↓, caspase-3 ↓	NF-κB ↓
HRS	Zhou et. al 2012113	Wistar rats	Sepsis (CLP)	HRS 2.5 or 10 ml/kg i.p.	TUNEL (+) ↓, caspase-3 ↓	N/A
HRS	Li et. al 201323	Sprague-Dawley rats	Sepsis (CLP)	HRS 5 ml/kg i.p.	TUNEL (+) ↓	N/A
HRS	Xu et. al 201322	Sprague-Dawley rats	Septic liver injury (LPS)	HRS 8 ml/kg/h i.v.× 6h	TUNEL (+) ↓, Smac ↓, caspase-3 ↓	NF-κB ↓, Smac ↓, MAPK (JNK/P38) ↓
2% H2	Liu et. al 201426	ICR mice	Septic brain injury (CLP)	Inhale 2% H2 1h (post-operation 1h and 6h)	TUNEL (+) ↓	Nrf2/HO-1 ↑
HRS HRM	Chen et. al 201536	ICR mice, UVECs-12	Sepsis (CLP) HUVECs (LPS)	HRS 5 ml/kg i.p., HRM 0.6 mmol/L	Annexin-V/PI ↓, caspase-3 ↓	Nrf2/HO-1 ↑
HRS	Zhang et. al 201511	Sprague-Dawley rats	Septic lung injury (LPS)	HRS 8 ml/kg/h i.v.× 6h	TUNEL (+) ↓, caspase-3 ↓	P38 MAPK ↓
HW	Iketani et. al 20176	C57BL/6 mice	Sepsis (LPS)	HW oral (72h before and after LPS)	TUNEL (+) ↓	HO-1 ↑, ET-1 ↑

HRS: hydrogen rich saline, HRM: hydrogen rich medium, HW: hydrogen water, LPS: Lipopolysaccharide, CLP: cecal ligation and puncture, GalN: D-galactosamine, i.p.: Intraperitoneal injection, i.v.: Intravenous injection, TUNEL: terminal deoxynucleotidyl transferase mediated dUTP nick end labeling, cPARP: cytoplasm poly ADP-ribose polymerase, ROS: reactive oxygen species, Smac: second mitochondria-derived activator of caspases.