NADPH Oxidase as a Therapeutic Target for Oxalate Induced Injury in Kidneys

Abstract

A major role of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes is to catalyze the production of superoxides and other reactive oxygen species (ROS). These ROS, in turn, play a key role as messengers in cell signal transduction and cell cycling, but when they are produced in excess they can lead to oxidative stress (OS). Oxidative stress in the kidneys is now considered a major cause of renal injury and inflammation, giving rise to a variety of pathological disorders. In this review, we discuss the putative role of oxalate in producing oxidative stress via the production of reactive oxygen species by isoforms of NADPH oxidases expressed in different cellular locations of the kidneys. Most renal cells produce ROS, and recent data indicate a direct correlation between upregulated gene expressions of NADPH oxidase, ROS, and inflammation. Renal tissue expression of multiple NADPH oxidase isoforms most likely will impact the future use of different antioxidants and NADPH oxidase inhibitors to minimize OS and renal tissue injury in hyperoxaluria-induced kidney stone disease.

L-Carnitine Protects Renal Tubular Cells Against Calcium Oxalate Monohydrate Crystals Adhesion Through Preventing Cells From Dedifferentiation

“…We investigated the effect of L-carnitine on COM attachment-induced dedifferentiation and subsequent COM crystals adhesion. Although there were not any literatures paying attention to L-carnitine in renal tubular epithelial cells dedifferentiation, its protective effects against ROS and NADPH, which are usually activated after COM /oxalate stimulation [23,24], have been reported abundantly. In current study, we discovered that with pre-treatment of L-carnitine, the loss of E-cadherin induced by COM attachment was inversed, and the increase of Vimentin was attenuated.…”

Mediators and mechanisms of heat shock protein 70 based cytoprotection in obstructive nephropathy

“…The NADPH oxidase family of enzymes has a major role catalyzing the production of superoxides and other ROS. In turn, they play an important role for cellular signal transduction; however, an excess may cause oxidative stress, currently known as a major cause of renal inflammation and subsequent damage (Joshi et al 2013). The proinflammatory state would be amplified by changes in renal antioxidants and ROS levels (Rinaldi Tosi et al 2011).…”

Rottlerin, a polyphenolic compound from the fruits of Mallotus phillipensis (Lam.) Müll.Arg., impedes oxalate/calcium oxalate induced pathways of oxidative stress in male wistar rats

“…inflammation resulting in calcium oxalate deposition in the renal tissue (Joshi et al 2013). To further unravel the mechanism underlying the effects of rottlerin on hyperoxaluric rats, the effect of rottlerin on NADPH oxidase activity was studied.…”

“…NADPH oxidase is considered as a major source of ROS in kidneys (Geiszt et al 2000). Oxalate and/or CaOx crystals induced ROS in renal tissue is also primarily produced by NADPH oxidase (Joshi et al 2013) and mitochondria (Khand et al 2002). In the view of oxidative imbalance caused by calcium oxalate crystals, a number of studies have pointed out the potential role of antioxidants towards its management.…”