Warholm M, Holmberg B, Högberg J, Kronevi T, Götharson A
Int J Tissue React. 1984;6(1):61-70.
The irritating aldehyde acrolein was injected intraperitoneally into mice. A single injection at 4 mg/kg gave rise to a 5-fold increase in plasma total lactate dehydrogenase (LDH) activity, with the peak after approximately 10 h. The pattern of LDH isoenzymes was not altered. Repeated injections (daily or weekly) caused a progressively less pronounced effect on the LDH activity. Experiments with formaldehyde and crotonaldehyde gave essentially the same results. The LD50 for acrolein i.p. in mice was increased from a level of 7 mg/kg to a level of 12 mg/kg by pretreatment with sublethal doses of 4 mg/kg/day for 5 days. Thus, the response to repeated acrolein injections, in terms of LDH and LD50, indicates an acquired tolerance against the irritant. Likewise, pretreatment with formaldehyde or crotonaldehyde could induce tolerance, in terms of LDH activity, towards a subsequent injection of acrolein. Histopathological examination revealed that spleen, adrenals and thymus were affected. The thymus markedly decreased in size after repeated injections of acrolein, crotonaldehyde or formaldehyde. Adrenalectomized mice given acrolein showed no thymus atrophy. A single injection of aldehyde caused an increased level of the adrenal hormone corticosterone in blood plasma. Adrenalectomized mice still showed a certain tolerance, in terms of LDH activity, after repeated injections of acrolein, but the increase in plasma LDH activity was smaller than for normal animals. Treatment with acrolein for six days did not change the level of reduced glutathione or the glutathione S-transferase activity in liver cytosol, but the rate of glutathione synthesis was increased. It is concluded that adrenalectomy does not completely prevent the development of tolerance in mice. It is possible that an increased metabolism can partially explain the acquired tolerance.
