Abstract
Oxidative stress produces macromolecules dysfunction and cellular damage. Renal ischemia-reperfusion injury (IRI) induces oxidative stress, inflammation, epithelium and endothelium damage, and cessation of renal function. The IRI is an inevitable process during kidney transplantation. Preliminary studies suggest that aminoguanidine (AG) is an antioxidant compound. In this study, we investigated the antioxidant effects of AG (50 mg/kg, intraperitoneal) and its association with molecular pathways activated by IRI (30 min/48 h) in the kidney. The antioxidant effect of AG was studied measuring GSSH/GSSG ratio, GST activity, lipoperoxidation, iNOS, and Hsp27 levels. In addition, we examined the effect of AG on elements associated with cell survival, inflammation, endothelium, and mesenchymal transition during IRI. AG prevented lipid peroxidation, increased GSH levels, and recovered the GST activity impaired by IRI. AG was associated with inhibition of iNOS, Hsp27, endothelial activation (VE-cadherin, PECAM), mesenchymal markers (vimentin, fascin, and HSP47), and inflammation (IL-1β, IL-6, Foxp3, and IL-10) upregulation. In addition, AG reduced kidney injury (NGAL, clusterin, Arg-2, and TFG-β1) and improved kidney function (glomerular filtration rate) during IRI. In conclusion, we found new evidence of the antioxidant properties of AG as a renoprotective compound during IRI. Therefore, AG is a promising compound to treat the deleterious effect of renal IRI.
Highlights
Aminoguanidine (AG) is a small, nontoxic molecule with different biological actions
We studied kidney damage by measuring glomerular filtration rate (GFR), acute kidney injury biomarker, and histological analysis
The Glomerular Filtration Rate (GFR) decreased by approximately 50% in mice subjected to renal IR compared with sham (476.7 ± 56.0 and 869.2 ± 62.0 μL/min/100 g body for IR and sham, respectively; p < 0.05)
Summary
It has been shown that AG inhibits the formation of highly reactive advanced glycosyla‐ tion end products (AGEs) associated with diabetes mellitus (DM) and decreases the com‐ plications related to proteinuria [1], retinopathy [2], and neuropathy [3]. Due to these ef‐ fects, AG was proposed as a therapeutic agent inhibiting AGEs formation [4]. The beneficial therapeutic properties of low doses of AG in other kidney diseases are poorly understood
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
