Pharmacokinetics of hydrogen administered intraperitoneally as hydrogen-rich saline and its effect on ischemic neuronal cell death in the brain in gerbils

Intraperitoneal administration of hydrogen (H₂)-containing saline inhibited neuronal cell death in ischemic stroke in a number of animal models, but it is unknown whether H₂ is absorbed from the abdominal cavity into the blood and reaches the brain. In this study, we investigated whether intraperitoneal administration of saline containing H₂ inhibits neuronal cell death caused by cerebral ischemia and measured the concentration of H₂ in the carotid artery and inferior vena cava (IVC). Gerbils were subjected to transient unilateral cerebral ischemia twice, and saline or H₂-rich saline was administered intraperitoneally three or seven times every 12 hours. We evaluated the number of apoptotic cells in the hippocampus and cerebral cortex on day 3 and the number of viable neurons in the hippocampus and cerebral cortex on day 7. In addition, a single dose of saline or H₂-rich saline was administered intraperitoneally, and blood H₂ levels in the carotid artery and IVC were measured. On day 3 of ischemia/reperfusion, the number of neurons undergoing apoptosis in the cortex was significantly lower in the H₂-rich saline group than in the saline group, and on day 7, the number of viable neurons in the hippocampus and cerebral cortex was significantly higher in the H₂-rich saline group. Intraperitoneal administration of H₂-rich saline resulted in large increases in H₂ concentration in the IVC ranging from 0.00183 mg/L (0.114%) to 0.00725 mg/L (0.453%). In contrast, carotid H₂ concentrations remained in the range of 0.00008 mg/ L (0.0049%) to 0.00023 (0.0146%). On average, H₂ concentrations in carotid artery were 0.04 times lower than in IVC. These results indicate that intraperitoneal administration of H₂rich saline significantly suppresses neuronal cell death after cerebral ischemia, even though H₂ hardly reaches the brain.