Oral administration of oxalate-enriched spinach extract as an improved methodology for the induction of dietary hyperoxaluric nephrocalcinosis in experimental rats

Abstract

Experimental induction of hyperoxaluria by ethylene glycol (EG) administration is disapproved as it causes metabolic acidosis while the oral administration of chemically synthesized potassium oxalate (KOx) diet does not mimic our natural system. Since existing models comprise limitations, this study is aimed to develop an improved model for the induction of dietary hyperoxaluria, and nephrocalcinosis in experimental rats by administration of naturally available oxalate rich diet. Male albino Wistar rats were divided into five groups. Group I, control; group II rats received 0.75% EG, group III rats fed with 5% KOx diet and group IV and V rats were administered with spinach extract of 250 and 500 mg soluble oxalate/day respectively, for 28 d. Urine and serum biochemistry were analyzed. After the experimental period, rats were sacrificed, liver and kidney tissue homogenates were used for antioxidant and lipid peroxidation assay. Relative change in expression of kidney injury molecule-1 (KIM-1) and crystal modulators genes in kidney tissues were evaluated. Tissue damage was assessed by histology studies of liver and kidney. Experimental group rats developed hyperoxaluria and crystalluria. Urine parameters, serum biochemistry, antioxidant profile, lipid peroxidation levels and gene expression analysis of experimental group II and III rats reflected acute kidney damage compared to group V rats. Histopathology results showed moderate hyperplasia in liver and severe interstitial inflammation in kidneys of group II and III than group V rats. Ingestion of naturally available oxalate enriched spinach extract successfully induced dietary hyperoxaluria and nephrocalcinosis in rats with minimal kidney damage.

Lemon Juice Formulations Modulate In Vitro Digestive Recovery of Spinach Phytochemicals

“…The range of oxalic acid mass fraction was 6.0−12.2 mg/g. Similar values were recorded by Akhtar et al ( 34 ) and Savage et al ( 35 ) in raw or boiled spinach and they were ten times lower than those found by Albert et al ( 36 ) in dried spinach water extract. Average oxalate dry mass fraction in this study was 8.97 mg/g whereas Wang et al ( 4 ) observed higher average oxalate mass fraction on fresh mass basis of 20.76 mg/g.…”

Dietary Oxalate Intake and Kidney Outcomes

“…Although increased urinary oxalate excretion and its dietary consumption are directly linked to kidney stones, oxalate crystal deposition in renal parenchyma is also responsible for nephrocalcinosis [ 102 ]. Mice fed with an oxalate-added spinach-derived extract developed crystalluria, hyperoxaluria and interstitial inflammation associated to nephrocalcinosis [ 103 ]. In humans affected by cystic fibrosis, the presence of absorptive hyperoxaluria has been linked to both nephrolithiasis and nephrocalcinosis [ 104 , 105 ].…”

High expression of SLC26A6 in the kidney may contribute to renal calcification via an SLC26A6-dependent mechanism

“…The potential mechanism might be that Slc26a6 led to the secretion and reabsorption of oxalate, resulting in higher oxalate concentration in urine and interstitium ( Marengo & Romani, 2008 ). A high-oxalate concentration could lead to tissue inflammation and crystal deposition in a short time ( Albert et al, 2017 ). Therefore, the lv-Slc26a6 group had the highest level of crystals and the siRNA-Slc26a6 group had the least level of crystals ( Fig.…”