Renal fibrosis is the common pathway for most forms of progressive renal disease. The Unilateral Ureteral Obstruction (UUO) model is used to cause renal fibrosis, where the primary feature of UUO is tubular injury as a result of obstructed urine flow. Furthermore, experimental UUO in rodents is believed to mimic human chronic obstructive nephropathy in an accelerated manner. Renal fibrosis is the common pathway for most forms of progressive renal disease. Removing the obstruction may not be sufficient to reverse fibrosis, so an accompanying treatment may be of benefit. In this review, we have done a revision on treatments shown to ameliorate fibrosis in the context of the UUO experimental model. The treatments inhibit the production of fibrotic and inflammatory proteins such as Transforming Growth Factor β1 (TGF-β1), Tumor Necrosis Factor α (TNF-α), collagen and fibronectin, Heat Shock Protein 47 (HSP47), suppress the proliferation of fibroblasts, prevent epithelial-to-mesenchymal transition, reduce oxidative stress, inhibit the action of the Nuclear Factor κB (NF-κB), reduce the phosphorylation of mothers against decapentaplegic homolog (SMAD) family members 2 and 3 (Smad2/3) or Mitogen-Activated Protein Kinases (MAPKs), inhibit the activation of the renin-angiotensin system. Summaries of the UUO experimental methods and alterations observed in the UUO experiments are included.

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Five-sixths nephrectomy (5/6NX) is a widely used model to study the mechanisms leading to renal damage in chronic kidney disease (CKD). However, early alterations on renal function, mitochondrial dynamics, and oxidative stress have not been explored yet. Curcumin is an antioxidant that has shown nephroprotection in 5/6NX-induced renal damage. The aim of this study was to explore the effect of curcumin on early mitochondrial alterations induced by 5/6NX in rats. In isolated mitochondria, 5/6NX-induced hydrogen peroxide production was associated with decreased activity of complexes I and V, decreased activity of antioxidant enzymes, alterations in oxygen consumption and increased MDA-protein adducts. In addition, it was found that 5/6NX shifted mitochondrial dynamics to fusion, which was evidenced by increased optic atrophy 1 and mitofusin 1 (Mfn1) and decreased fission 1 and dynamin-related protein 1 expressions. These data were confirmed by morphological analysis and immunoelectron microscopy of Mfn-1. All the above-described mechanisms were prevented by curcumin. Also, it was found that curcumin prevented renal dysfunction by improving renal blood flow and the total antioxidant capacity induced by 5/6NX. Moreover, in glomeruli and proximal tubules 5/6NX-induced superoxide anion production by uncoupled nitric oxide synthase (NOS) and nicotinamide adenine dinucleotide phosphate oxidase (NOX) dependent way, this latter was associated with increased phosphorylation of serine 304 of p47phox subunit of NOX. In conclusion, this study shows that curcumin pretreatment decreases early 5/6NX-induced altered mitochondrial dynamics, bioenergetics, and oxidative stress, which may be associated with the preservation of renal function. © 2016 BioFactors, 43(2):293-310, 2017.

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