Abstract
Antipyretic drugs are widely used to manage fever and pain and are generally regarded as safe when administered within recommended therapeutic ranges. Nevertheless, concerns remain regarding the potential biological effects associated with repeated or sub-chronic exposure. The present study evaluated the hematological, histopathological, and molecular effects of two commonly used antipyretics, paracetamol and ibuprofen, following repeated administration in male albino mice. Hematological analysis revealed drug-related alterations in selected blood parameters, with more pronounced changes observed in ibuprofen-treated groups, while paracetamol exposure was associated with comparatively milder effects. Qualitative histopathological examination demonstrated organ-specific structural alterations in the testes, liver, kidneys, and stomach, which were generally mild in nature and more frequently observed at higher experimental dose levels. No evidence of overt testicular failure or severe tissue damage was detected within the exposure period. At the molecular level, repeated exposure to paracetamol and ibuprofen was associated with downregulation of TNF-α and connexin 43 mRNA expression in peripheral blood, suggesting early systemic transcriptional responses accompanying the observed histological changes. However, molecular findings were limited to mRNA expression analysis and did not include protein-level or tissue-specific validation. Overall, the results indicate that repeated sub-chronic exposure to paracetamol and ibuprofen at therapeutic-equivalent dose ranges may be associated with early hematological, histological, and molecular alterations in mice. These findings highlight the importance of cautious and rational use of widely prescribed antipyretic drugs and underscore the need for further studies to elucidate long-term safety, underlying mechanisms, and tissue-specific functional outcomes.