FOLINIC ACID PROTECTION AGAINST HEMATOPOIETIC DEPRESSION INDUCED BY NITROUS-OXIDE IN RATS

We studied the degree of hematopoietic depression and spontaneous reco very of depressed hematopoietic cells with 50% nitrous oxide-oxygen in halation for 6 or 12 h in 120 Sprague-Dawley rats. Bone marrow and blo od were sampled serially immediately after, 1 day, 3 days, and 1 wk fo llowing nitrous oxide inhalation. After 1 wk of culturing of hematopoi etic stem cells, the number of the colony-forming units of granulocyte s and monocytes and the colony-forming units of T lymphocytes grown fr om bone marrow and blood were counted. There was no change in the numb er 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 ma y depress the early phase of differentiation of hematopoietic stem cel ls such as granulocytes, monocytes, and lymphocytes as well as erythro cytes. Also, the degree of suppression was more intense after 12 h tha n after 6 h of inhalation. That is, the length of inhalation time corr esponds to the intensity and rapidity of suppression. To evaluate the protective effect of folinic acid against hematopoietic depression, fo linic acid (0.1 mg/0.3 mL) was injected intraperitoneally before or af ter nitrous oxide inhalation. The groups injected with folinic acid sh owed significant increase in the number of colonies, especially in the group receiving folinic acid 12 h and 1 h before nitrous oxide inhala tion (P < 0.001). Pretreatment with folinic acid may prevent the hemat opoietic depression caused by the prolonged and repeated use of nitrou s oxide.