Activation of sirtuin 3 and maintenance of mitochondrial homeostasis by artemisinin protect against diclofenac-induced kidney injury in rats.

Nonsteroidal anti-inflammatory drug (NSAID)-induced kidney injury is one of the most common causes of renal failure. The exact pathogenesis of NSAID induced kidney injury is not fully known and the treatment is still challenging. Artemisinin (ART) gains more attention by its potent biological activities in addition to its antimalarial effect. In our research, we evaluated the preventive and therapeutic effects of ART in Diclofenac (DIC) induced kidney injury through its effect on mitochondria and regulation of sirtuin 3 (SIRT3). Thirty adult male Sprague Dawley rats were divided into five groups: control, ART, DIC, DIC + ART prophylactic, and DIC followed + ART therapeutic groups. At the end of the study, animals were scarified and the following parameters were evaluated: serum urea and creatinine, renal malondialdehyde (MDA), superoxide dismutase (SOD) and nitrate. SIRT3 was detected by western blotting and real-time PCR. Mitochondrial related markers (PGC-1α, Drp1, and mitochondrial ATP) were detected by immunoassay. Caspase-3 and LC3 II expression in kidney tissues were demonstrated by immune-histochemical staining. The kidney specimens were stained for H&E and PAS special stain. Electron microscopy was done to detect mitochondrial morphology. ART improved renal function test, oxidative stress, SIRT3 level, mitochondrial function, LC3 II expression and decrease caspase-3. Histopathological examination confirmed ART alleviation as determined by light or electron microscopy. ART can modulate biochemical and pathological changes in DIC-induced kidney injury and can be considered a new possible therapeutic approach for DIC-induced kidney injury through its effect on SIR3 and maintenance of mitochondrial homeostasis.