Vol.:(0123456789) 1 3 World J Urol DOI 10.1007/s00345-017-2083-8 ORIGINAL ARTICLE Effect of endoplasmic reticulum stress inhibition on hyperoxaluria‑induced oxidative stress: influence on cellular ROS sources Rishi Bhardwaj 1  · Chanderdeep Tandon 2  · Devinder K. Dhawan 1  · Tanzeer Kaur 1   Received: 29 June 2017 / Accepted: 17 August 2017 © Springer-Verlag GmbH Germany 2017 Conclusions Therefore, suggesting the major role of ER in hyperoxaluric manifestations thereby providing an opportu- nity to target ER stress for future therapeutic interventions. Keywords 4-PBA · Hyperoxaluria · ER stress · Mitochondria · NADPH oxidase Abbreviations ATF4 Activating transcription factor 4 CHOP C/EBP homologous protein ER Endoplasmic reticulum GRP78 Glucose-regulated protein 78 MCP-1 Monocyte chemoattractant protein 1 NOX NADPH oxidase 4-PBA 4-Phenylbutyric acid ROS Reactive oxygen species UPR Unfolded protein response XBP-1 X-box binding protein Introduction Hyperoxaluria has been a known culprit due to its contri- bution in the genesis of calcium oxalate crystallisation. Clinically, hyperoxaluric condition can be categorised into primary and secondary hyperoxaluria where the former is an inherited error of metabolism due to defective enzyme activity (Alanine: Glyoxylate Aminotransferase) and the lat- ter being a consequence of increased oxalate ingestion which may also lead to oxalate toxicity [1]. Oxalate as a substance is synthesised in the human body but it is not metabolised further which under certain conditions can be toxic for the normal functioning of cellular processes [2]. Some of the major known natural precursors of oxalate are ascorbic acid, hydroxyl-L-proline, glycine and serine along with ethylene Abstract Purpose Hyperoxaluria-induced calcium oxalate crystal- lisation is associated with the generation of reactive oxygen species (ROS) via mitochondria and NADPH oxidase. Endo- plasmic reticulum (ER) has emerged as an organelle which could influence mitochondrial functioning and ROS genera- tion. Plugging an upstream pathway of mitochondrial and NADPH oxidase-induced ROS generation may have better prophylaxis. Therefore, we propose to investigate the linkage of hyperoxaluria-induced ROS generation with ER stress by inhibiting the later with 4-Phenylbutyric acid (4-PBA). Methods Male wistar rats were divided into three groups: a normal control group, an ethylene glycol with ammonium chloride-induced hyperoxaluric group (EA) and a third group which has hyperoxaluric animals given 4-PBA at a dose of 300 mg/kg. After 9 days of treatment, animals were sacrificed and renal tissues were analysed for histopatho- logical examination, ROS, mitochondrial dysfunction, ER stress markers, inflammatory markers and NADPH oxidase subunits expression. Results Hyperoxaluric rats exhibited a significant increase in the levels of ROS, subsequently up-regulated levels of ER stress markers, inflammatory indicators, NADPH oxi- dase subunits and compromised mitochondrial functioning. However, ER stress amelioration appreciably curtailed the alterations caused by hyperoxaluric abuse. * Tanzeer Kaur tanzeer.kaur@pu.ac.in 1 Department of Biophysics, Panjab University, Chandigarh, India 2 Amity Institute of Biotechnology, Amity University, Noida, UP, India