Paracetamol and stress: sexual dimorphism of the effect on the thymus, spleen, and hematological parameters

The immune system is one of the most sensitive targets of the stress response, as reflected by alterations in lymphoid organs and hematological parameters. Paracetamol, one of the most widely used analgesics, is traditionally studied as a hepatotoxic agent; however, its effects on immunohematological parameters remain insufficiently explored, especially in combination with chronic stress. The aim of the study was to assess the effects of 28-day administration of paracetamol (1000 mg/kg), including under conditions of chronic unpredictable stress, on body weight, thymus and spleen weight coefficients, and hematological parameters in male and female rats. In males, chronic stress caused a significant decrease in leukocyte count (to 5,7×10⁹/L; p=0,001), whereas paracetamol increased leukocyte levels compared to stress alone (p=0,001). Paracetamol reduced hemoglobin levels (129,5 g/L), while in combination with stress, hemoglobin was increased (141,1 g/L; p=0,001). In females, these changes were not observed; however, a significant decrease in platelet count was detected in all experimental groups (p=0,001). The thymus weight coefficient in females decreased after paracetamol administration (1,08; p 0,01), whereas in males it remained unchanged. A reduction in spleen weight coefficient was observed only in males under stress and combined exposure (p≤0,02).The data indicate a sex-dependent pattern of immunohematological changes associated with paracetamol administration, both alone and in combination with chronic stress. At the same time, the absence of endocrine parameter assessment does not allow the observed differences to be unequivocally interpreted as evidence of a stress-protective effect of paracetamol; these findings require further investigation with the inclusion of markers of hypothalamic-pituitary-adrenal and gonadal regulation.

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