Pitavastatin attenuates cisplatin-induced renal injury by targeting MAPK and apoptotic pathways

Abstract

These authors contributed equally to the research. AbstractObjective Anti-neoplastic drug cisplatin is prescribed widely for treatment of a variety of malignancies. Its use has been restricted lately due to severe renal toxicity. The purpose of current study was to investigate the effect of pitavastatin (a hypolipidaemic drug) in cisplatin-induced acute kidney injury in rats. Method Male Wistar rats (150-200 g) were treated with different doses of pitavastatin (0.16, 0.32 and 0.64 mg/kg per day p.o.; 10 days). On 7th day of the study, rats were administered cisplatin (8 mg/kg i.p.). Rats were euthanized (11th day), and blood and tissues were processed to evaluate biochemical, histopathological and ultrastructural parameters along with the analysis of immunohistochemistry and DNA-fragmentation studies. Protein expressions were analysed to demonstrate the underlying molecular mechanisms. Key findings In the study group with cisplatin insult, KFT parameters were found to be elevated, concentration of apoptotic markers was found to be increased, histopathological and ultramicroscopical architecture was found to be distorted and the expression of MAPK proteins was also found to be elevated as compared to the normal group rats. Pitavastatin treatment alleviated all these anomalies. Conclusion Cisplatin-induced acute renal injury was improved on administration of pitavastatin via inhibition of MAPK and apoptotic pathway.

Protective Effects of Simvastatin on Endotoxin-Induced Acute Kidney Injury through Activation of Tubular Epithelial Cells’ Survival and Hindering Cytochrome C-Mediated Apoptosis

“…One previous study showed that atorvastatin ameliorated contrast-induced nephropathy and reduced the extent of renal tubular cell apoptosis that is associated with the decreased expression of proapoptotic Bax/caspase-3 and increased Bcl-2 [ 17 ]. Another study that demonstrated the renoprotective effects of pitavastatin on cisplatin-induced AKI pointed to suppression of the mitogen-activated protein kinase (MAPK)/NF-kB/inflammation axis and intrinsic apoptotic pathway [ 18 ].…”

Renoprotective Effect of Pitavastatin against TAA-Induced Renal Injury: Involvement of the miR-93/PTEN/AKT/mTOR Pathway

“…While previous studies have shown the nephroprotective efects of statins, including pitavastatin [45][46][47][48][49][50][51], the specifc involvement of the miR-93/PTEN/Akt/mTOR pathway in mediating these efects has not been elucidated in vivo in the context of xenobiotic-induced kidney injury. Our study is the frst to demonstrate that pitavastatin attenuates TAAinduced kidney damage in rats by regulating this essential signaling cascade.…”

Pitavastatin induces caspase‐mediated apoptotic death through oxidative stress and DNA damage in combined with cisplatin in human cervical cancer cell line

“…In these cells, the expression of cleaved caspase‐3 and cleaved PARP increased significantly in a dose‐dependent manner after treatment with fluvastatin at concentrations ranging from 0 to 10 μM at exposure times of 12 hours (Qi et al, 2013). Along with the studies showing that PITA induces apoptosis, there are also researchers stating that its effect on apoptosis is quite indirect (Kaushik et al, 2019; Voss et al, 2021). The requirement of studies to be done in this scope is clear.…”