Abstract
Acute kidney injury (AKI) has been widely recognized as an important risk factor leading to the occurrence and progression of chronic kidney disease (CKD). Thus, development of the strategies in retarding the transition of AKI to CKD is becoming a hot research field. Recently, accumulating evidence suggested a pathogenic role of mitochondrial dysfunction in both AKI and CKD. Therefore, in the present study, we evaluated the effect of mitochondrial complex 1 inhibition by rotenone on the chronic renal damage induced by acute ischemia-reperfusion. The mice were treated with 45 min unilateral renal ischemia and reperfusion (I/R) to induce an acute renal injury. After three days of I/R injury, rotenone at a dose of 200 ppm in food was administered to the mice. Strikingly, after three weeks treatment with rotenone, we found that the unilateral I/R-induced tubular damage, tubulointerstitial fibrosis were all attenuated by rotenone as determined by the tubular injury score, Masson staining, and the levels of collagen-I, collagen-III, fibronectin, PAI-1, and TGF-β. Meanwhile, the enhanced inflammatory markers of TNF-α, IL-1β, IL-6, and IL-18 and apoptotic markers of Bax and caspase-3 were all significantly blunted by inhibiting mitochondrial complex-1. Moreover, rotenone treatment also partially protected the mitochondria as shown by the restoration of mitochondrial SOD (SOD2), ATPB, and mitochondrial DNA copy number. These findings suggested that inhibition of mitochondrial complex-1 activity by rotenone could retard the progression of AKI to CKD probably via protecting the mitochondrial function to some extent.