Vincamine protects against cisplatin induced nephrotoxicity via activation of Nrf2/HO-1 and hindering TLR4/ IFN-γ/CD44 cells inflammatory cascade

Cisplatin is a commonly prescribed chemotherapeutic agent for the treatment of different types of solid tumors. However, the high incidence of cisplatin-induced nephrotoxicity largely restricts its clinical efficacy in absence of both preventive and treatment options to combat its serious and life-threatening effects. Therefore, the current study investigated the reno-protective molecular mechanisms of vincamine against cisplatin nephrotoxicity. Vincamine (40 mg/kg P.O.) was given for 7 days, cisplatin was injected as single dose (10 mg/kg i.p.) at the seven day of the experiments. Animals were sacrificed after 72 h of cisplatin injection to allow nephrotoxicity. Vincamine pretreatment improved kidney functions and decreased kidney function tests as urea, creatinine and kidney injury molecule-1 (KIM-1), as well as it exhibited antioxidant properties by restoring balance between pro and anti-oxidants of malondialdehyde (MDA), myeloperoxidase (MPO), nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1). Moreover, vincamine hindered the inflammatory cascade via mediating Toll like receptor 4 (TLR4)- interferon gamma (IFNγ)-CD44 cells pathway and transforming growth factor beta (TGFβ1). Additionally, vincamine retained DNA fragmentation. In conclusion, vincamine represents a promising intervention in limiting cisplatin nephrotoxicity by its anti-oxidant, anti-inflammatory, antiapoptotic mechanistic activities. Therefore, vincamine can be used as adjunct therapy with cisplatin to mitigate cisplatin-induced-AKI.