N-acetyl cysteine increases cellular dysfunction in progressive chronic kidney damage after acute kidney injury by dampening endogenous antioxidant responses

Oxidative stress and mitochondrial dysfunction exacerbate acute kidney injury (AKI) but their role in any associated progress to chronic kidney disease (CKD) remains unclear. Antioxidant therapies often benefit AKI but their benefits in CKD are controversial since clinical and pre-clinical investigations often conflict. Here we examined the influence of the antioxidant, N-acetyl cysteine (NAC) on oxidative stress and mitochondrial function during AKI (20-minute bilateral renal ischemia plus reperfusion/IR) and progression to chronic kidney pathologies in mice. NAC (5% in diet) was given to mice 7 days prior and up to 21 days post-IR (21d-IR). NAC treatment: prevented proximal tubular epithelial cell apoptosis at early IR (40-min post-ischemia), yet enhanced interstitial cell proliferation at 21d-IR; increased Transforming growth factor-β1 expression independent of IR time; and significantly dampened nuclear factor-like 2-initiated cytoprotective signalling at early IR. Long-term, NAC enhanced cellular met...