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 (H(2))-containing saline inhibited neuronal cell death in ischemic stroke in a number of animal models, but it is unknown whether H(2) is absorbed from the abdominal cavity into the blood and reaches the brain. In this study, we investigated whether intraperitoneal administration of saline containing H(2) inhibits neuronal cell death caused by cerebral ischemia and measured the concentration of H(2) in the carotid artery and inferior vena cava (IVC). Gerbils were subjected to transient unilateral cerebral ischemia twice, and saline or H(2)-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 H(2)-rich saline was administered intraperitoneally, and blood H(2) 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 H(2)-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 H(2)-rich saline group. Intraperitoneal administration of H(2)-rich saline resulted in large increases in H(2) concentration in the IVC ranging from 0.00183 mg/L (0.114%) to 0.00725 mg/L (0.453%). In contrast, carotid H(2) concentrations remained in the range of 0.00008 mg/L (0.0049%) to 0.00023 (0.0146%). On average, H(2) concentrations in carotid artery were 0.04 times lower than in IVC. These results indicate that intraperitoneal administration of H(2)-rich saline significantly suppresses neuronal cell death after cerebral ischemia, even though H(2) hardly reaches the brain.