Salicylic acid attenuates paclitaxel-induced toxicity by modulating interleukin expression: an in vivo study

Paclitaxel (PAX) is an effective chemotherapeutic agent for treating various cancers but is associated with side effects such as hepatotoxicity, neurotoxicity, and myelosuppression. To mitigate these toxicities, adjunct therapies like salicylic acid (SA), a plant-derived compound with anti-inflammatory, antioxidant, and cytoprotective properties, have been explored. This study investigates SA's potential to counteract PAX's cytotoxic effects, focusing on hepatic tissue. Thirty-five BALB/cJ mice were treated with PAX and SA, either individually or in combination (low and high doses), for 14 days. Post-treatment, biochemical and histological analyses were performed. ELISA assays measured serum levels of inflammatory markers IL-1β, IL-6, and TNF-α, while caspase-3/7 activity was evaluated to assess apoptosis. qPCR assessed gene expression related to apoptosis (CASP1, CASP3, Bcl-2). Results showed that PAX significantly increased serum levels of inflammatory markers, which were reduced by SA treatment. PAX also elevated caspase-3/7 activity, but co-treatment with SA suppressed this effect. Histological analysis revealed that low-dose SA alleviated PAX-induced necrosis and inflammation in the liver, kidney, and spleen. Moreover, PAX alone significantly upregulated CASP1 and CASP3 expression, while co-treatment with SA significantly downregulated these genes. These findings highlight the protective role of SA in reducing PAX-induced toxicity, particularly in hepatic tissues, suggesting that SA could be a potential adjunct therapy for minimizing chemotherapy-related side effects.