Table 1.

Radioprotective effects of H₂ in cell free system, cells, animal models and clinical trials.

Damages/Damage Models	Species/Cells	Effects of H2	Ref. No.
Cell-free system		•OH is produced by the Fenton reaction and water radiolysis, and it was reduced by H2.	[48]
Cognitive impairment	Rats	Radiation-induced cognitive dysfunction was protected by H2-rich water.	[36]
Immune dysfunction	AHH-1 cells	Pretreatment with H2-rich PBS prior to radiation reduced the levels of MDA and 8-OHdG.	[37]
	AHH-1 cells	Pretreatment with H2-rich saline increased the viability of AHH-1 cells and inhibited apoptosis.	[38]
	AHH-1 cells	Pretreatment with H2-rich medium reduced •OH induced by radiation.	[39]
	Mice	H2-rich saline protected immunocytes from radiation-induced apoptosis.	[39]
	Mice	H2-rich saline protected against radiation-induced immune dysfunction.	[40]
Lung damage	A549 cells	H2-rich PBS suppressed ROS production, and improved oxidative stress and apoptosis markers.	[41]
	Mice	H2 gas inhibited not only acute lung damage, but also chronic lung damage.	[41]
Myocardial damage	Mice	H2-rich water protected against radiation-induced myocardium damage.	[42]
	Rats	H2-rich water protected against radiation-induced myocardium damage.	[43]
Gastrointestinal damage	HIEC	H2-rich PBS inhibited apoptosis and increased the cell viability of HIEC.	[37]
	Mice	H2-rich saline protected against radiation-induced gastrointestinal disorders.	[38]
	Mice	H2 water ameliorated radiation-induced gastrointestinal toxicity.	[44]
	IEC-6 cells	H2-rich medium improved survival and inhibited ROS production.	[45]
	Mice	H2-rich saline improved mouse survival and intestinal mucosal damage and function.	[45]
Hematopoietic cell injury	Mice	H2-rich water ameliorated radiation-induced hematopoietic stem cell injury.	[46]
Spermatogenesis and hematopoiesis disorders	Mice	H2-rich saline protected spermatogenesis and hematopoietic functions of irradiated mice.	[47]
Testicular damage	Rats	H2-rich saline protected against radiation-induced testicular damage.	[49]
Skin damage	HaCaT cells	H2-rich medium protected HaCaT cells from radiation injury by improving the survival rate.	[50]
	Rats	H2-rich saline reduced the severity of dermatitis, accelerated tissue recovery, and inhibited weight loss.	[50]
	Rats	Prior inhalation of H2 gas mitigated radiation-induced skin damage.	[51]
	Rats	H2-rich water promoted wound healing in radiation-induced skin lesions.	[52]
Cartilage damage	BMSC	H2-rich medium increased cell viability and differentiation potential.	[53]
	Rats	H2-rich saline protected against the osteonecrosis of jaw cartilage induced by radiation.	[53]
Thymic lymphoma	Mice	H2-rich saline protected against radiation-induced thymic lymphoma.	[54]
Impaired QOL	Humans	H2-rich water improved side effects of poor QOL by radiation therapy.	[23]
Bone marrow damage	Humans	H2 gas inhalation protected bone marrow damage in cancer patients receiving IMRT.	[24,25]

H₂: molecular hydrogen; •OH: hydroxy radical; AHH-1: human lymphocyte cell; MDA: malondialdehyde; 8-OHdG: 8-hydroxydeoxyguanosine; ROS: reactive oxygen species; HIEC: human intestinal crypt cell; IEC-6: intestinal crypt epithelial cell; HaCaT: human keratinocyte cell; BMSC: marrow-derived mesenchymal stem cell; QOL: quality of life; IMRT: intensity-modulated radiation therapy; Ref.: references.