Folinic acid protection against hematopoietic depression induced by nitrous oxide in rats

We studied the degree of hematopoietic depression and spontaneous recovery of depressed hematopoietic cells with 50% nitrous oxide-oxygen inhalation for 6 or 12 h in 120 Sprague-Dawley rats. Bone marrow and blood were sampled serially immediately after, 1 day, 3 days, and 1 wk following nitrous oxide inhalation. After 1 wk of culturing of hematopoietic stem cells, the number of the colony-forming units of granulocytes and monocytes and the colony-forming units of T lymphocytes grown from bone marrow and blood were counted. There was no change in the number of colonies immediately after inhalation compared with the control group, but there was a significant decrease in the number of colonies 1 and 3 days after inhalation (P < 0.001), and 1 wk after inhalation, there was spontaneous recovery without any treatment. Nitrous oxide may depress the early phase of differentiation of hematopoietic stem cells such as granulocytes, monocytes, and lymphocytes as well as erythrocytes. Also, the degree of suppression was more intense after 12 h than after 6 h of inhalation. That is, the length of inhalation time corresponds to the intensity and rapidity of suppression. To evaluate the protective effect of folinic acid against hematopoietic depression, folinic acid (0.1 mg/0.3 mL) was injected intraperitoneally before or after nitrous oxide inhalation. The groups injected with folinic acid showed significant increase in the number of colonies, especially in the group receiving folinic acid 12 h and 1 h before nitrous oxide inhalation (P < 0.001). Pretreatment with folinic acid may prevent the hematopoietic depression caused by the prolonged and repeated use of nitrous oxide.