Sex-dependent differences in the activities of acetylsalicylic acid-esterases in mouse kidneys

Acetylsalicylic acid (ASA), the most used drug worldwide, is hydrolyzed to salicylic acid and acetate by esterases present in tissues of several species including humans. Sex differences in drug metabolism by rodent liver are documented in the literature. In this paper we report a difference in the activities of the esterases (ASA-esterase I and II) in the kidneys of male and female mice. In this species there is no difference between males and females in liver ASA-esterases (ASA-esterase I: males 38.5 +/- 7.9 (N = 5) and females 31.6 +/- 7.6 (N = 5) nmol of salicylic acid formed min-1 mg protein-1, P > 0.05; ASA-esterase II: males 77.3 +/- 17.4 (N = 5) and females 61.4 +/- 15.1 (N = 5) nmol of salicylic acid formed min-1 mg protein-1, P > 0.05). However, in the kidneys males presented a much higher enzyme activity than females (ASA-esterase I: males 25.2 +/- 6.3 (N = 5) and females 6.8 +/- 0.6 (N = 5) nmol of salicylic acid formed min-1 mg protein-1, P < 0.0002; ASA-esterase II: males 79.8 +/- 10.1 (N = 5) and females 13.0 +/- 1.1 (N = 5) nmol of salicylic acid formed min-1 mg protein-1, P < 0.0001). The difference between sexes observed in mouse kidneys could serve as a model to study the molecular basis of this sex difference and also to determine the possible involvement of pituitary and gonadal hormones in this difference in ASA-esterase activities since these hormones control the sex differences in rodent liver enzyme activity.