Role of personalized medicine in silico

Hemorrhagic Cystitis (HC) is the primary side effect associated with the use of cyclophosphamide (CYP) in cancer patients. Acrolein, the urotoxic metabolite of CYP, induces oxidative stress, lipid peroxidation, and generation of proinflammatory cytokines leading to urothelial damage, hemorrhage, edema, and inflammation. Isovanillin, a plant-derived phenolic aldehyde, has shown antioxidant and anti-inflammatory activities in chemically induced rodent models. Therefore, in the present study, we investigated the uroprotective potential of isovanillin in female Sprague Dawley rats having HC induced by CYP (150 mg/Kg, 1, 4, and 7th day once i.p.). Three doses of isovanillin (5, 10, and 20 mg/kg) were evaluated in rats. On the 8th day, the urinary bladder samples were isolated and collected for in vitro studies. Pre-treatment with isovanillin decreased bladder weight, edema, hemorrhage, and nociception scoring in rats. Isovanillin also increased GSH, GST, and CAT activity and reduced lipid peroxidation in rats treated with CYP. Expression of TNF-α, Caspase 1, and iNOS were reduced in the isovanilline pretreatment groups while the expression of SOD increased. In silico studies presented isovanillin as a strong candidate for antioxidant, and anti-inflammatory activities with high lipophilicity, bioavailability, and safety profile. The findings of the current study present isovanillin as a uroprotective, antioxidant, and anti-inflammatory agent against HC induced by CYP. Consequently, isovanillin has the potential to be used as a potential adjuvant drug for CYP-based chemotherapy.