Heme Oxygenase‐1 Mediated Protective Effects of Linalool on Rifampicin‐Induced Spleen Toxicity Through the PI3K/Akt Pathway

ABSTRACT Rifampicin (RF) is a primary anti‐tuberculosis medication utilized in tuberculosis treatment, and its concurrent administration with other medications, as well as the duration of therapy, may result in adverse effects. While the hepatotoxicity of RF is established, its impact on the spleen remains unexamined. Thus, our study aimed to investigate the impact of RF on the spleen and the protective role of Linalool (LN), a monoterpene, through the Heme oxygenase‐1 (HO‐1) enzyme pathway, with biochemical analyses, oxidative stress parameters, protein levels, and histopathological assessments. In the study, thirty healthy adult male Sprague‐Dawley rats were randomly allocated into five groups: control, solvent control (dimethyl sulfoxide ‐ DMSO), RF, LN, and RF + LN. Spleen tissues and blood specimens were collected from the rats for examination. RF markedly elevated total and indirect bilirubin, Fe 2+ , HO‐1, and MDA levels, while diminishing GSH levels. Conversely, in the RF + LN group, total and indirect bilirubin, Fe 2+ , HO‐1, and MDA levels were dramatically reduced, whereas GSH levels were elevated. Histopathologically, RF‐induced defects were ameliorated in the LN‐treated cohorts. In conclusion, rifampicin exhibited toxic effects on the spleen, which were mitigated by LN.