Superoxide overproduction and kidney fibrosis: a new animal model

Abstract

Objective To establish whether the mutation in the Immp2L gene induces renal fibrosis and whether aging exacerbates renal morphology in mice.Methods Female mutant mice with mutation in the inner mitochondrial membrane peptidase 2-like protein at 3 and 18 months of age were used. Renal fibrosis was analyzed using classic fibrosis score, Masson’s trichrome staining, and analysis of profibrotic markers using real time polymerase chain reaction (superoxide dismutase 1, metalloproteinase-9, erythropoietin, transforming growth factor beta), and immunostaining (fibroblasts and Type IV collagen). Oxidative stress markers were determined by immunohistochemistry. The number of renal apoptotic cells was determined. Renal function was estimated by serum creatinine.Results Young mutant mice had significantly more glomerulosclerosis than age-matched mice (p=0.034). Mutant mice had more tubular casts (p=0.025), collagen deposition (p=0.019), and collagen type IV expression (p<0.001). Superoxide dismutase 1 expression was significantly higher in young mutants (p=0.038). Old mutants exhibited significantly higher expression of the fibroblast marker and macrophage marker (p=0.007 and p=0.012, respectively). The real time polymerase chain reaction of metalloproteinase-9 and erythropoietin were enhanced 2.5- and 6-fold, respectively, in old mutants. Serum creatinine was significantly higher in old mutants (p<0.001).Conclusion This mutation altered renal architecture by increasing the deposition of extracellular matrix, oxidative stress, and inflammation, suggesting a protective role of Immp2L against renal fibrosis.

Oxidative stress and inflammation following sub-lethal oral exposure of cypermethrin in rats: mitigating potential of epicatechin

“…SOD, the first enzyme in the antioxidant defense converts superoxide radicals to form H 2 O 2 to prevent the deleterious effects of oxygen radicals in the tissues. The increase in SOD activity implies a compensatory adaptive response to the increased presence of free radicals in the liver and kidney of the CYP-treated rats, in order to mitigate the toxic effects of the ROS generated by the pyrethroid [64]. CAT, a ubiquitous enzyme found in both soluble and membrane-bound forms catalyzes the decomposition of H 2 O 2 to H 2 O [65].…”

The aging kidney and the nephrotoxic effects of mercury

“…This cycle of events is thought to initiate other oxidative events that may lead to mitochondrial destabilization, cellular injury and cellular aging (Poulose and Raju 2014). These events may promote inflammation and enhanced deposition of extracellular matrix, which results in interstitial and parenchymal fibrosis and acute kidney injury (Guimaraes-Souza et al 2015; Small et al 2012; Akcay et al 2009; Kinsey et al 2008). …”

Tetrahydrobiopterin (BH4) Supplementation Prevents the Cardiorenal Effects of Diabetes in Mice by Reducing Oxidative Stress, Inflammation and Fibrosis

“…Glomerular pathological analysis was performed by a blinded investigator, scoring the degree of fibrosis, glomerular hypertrophy, and mesangial expansion according to previous reports [ 21 , 22 , 23 , 24 ].…”