Cancer remains one of the leading global causes of death, accounting for approximately one in every six deaths, with its prevalence steadily rising due to factors like aging populations, lifestyle habits such as smoking, unhealthy diets, obesity, physical inactivity, and air pollution. The present study is driven by the need to find effective treatments for cyclophosphamide (CP)-induced organ toxicity, especially lung damage caused by its toxic metabolite acrolein. CP’s use is limited due to oxidative stress, antioxidant depletion, and increased pro-inflammatory cytokines leading to cell death and tissue injury. Existing therapies are inadequate, highlighting the need for safer, more effective protective strategies.

The comprehensive evaluation of biochemical and histological markers reveals that cilnidipine, particularly at a higher dose, mitigates oxidative damage, reduces pro-inflammatory cytokine levels, and maintains tissue integrity. Its dual calcium channel blocking ability, coupled with its capacity to activate antioxidant defenses and suppress inflammatory pathways, underscores its therapeutic potential beyond hypertension. The findings suggest that cilnidipine can be repurposed as an adjunctive treatment in cancer therapy to reduce organ toxicity associated with cyclophosphamide and possibly other chemotherapeutic agents.