Nephroprotective Effect of Pleurotus ostreatus and Agaricus bisporus Extracts and Carvedilol on Ethylene Glycol-Induced Urolithiasis: Roles of NF-κB, p53, Bcl-2, Bax and Bak.

Hossam Ebaid,Ibrahim M. Alhazza,El-Shaymaa El-Nahass,Osama M. Ahmed,Mahmoud Ragab

doi:10.3390/biom10091317

Hossam Ebaid, Ibrahim M. Alhazza + Show 3 more

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https://doi.org/10.3390/biom10091317

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Abstract

This study was designed to assess the nephroprotective effects of Pleurotus ostreatus and Agaricus bisporus aqueous extracts and carvedilol on hyperoxaluria-induced urolithiasis and to scrutinize the possible roles of NF-κB, p53, Bcl-2, Bax and Bak. Phytochemical screening and GC-MS analysis of mushrooms’ aqueous extracts were also performed and revealed the presence of multiple antioxidant and anti-inflammatory components. Hyperoxaluria was induced in Wistar rats through the addition of 0.75% (v/v) ethylene glycol in drinking water for nine weeks. The ethylene glycol-administered rats were orally treated with Pleurotus ostreatus and Agaricus bisporus aqueous extracts (100 mg/kg) and carvedilol (30 mg/kg) daily during the last seven weeks. The study showed that Pleurotus ostreatus, Agaricus bisporus and carvedilol all successfully inhibited ethylene glycol-induced histological perturbations and the elevation of serum creatinine, serum urea, serum and urinary uric acid, serum, urinary and kidney oxalate, urine specific gravity, kidney calcium, kidney NF-κB, NF-κB p65, NF-κB p50, p53, Bax and Bak expressions as well as serum TNF-α and IL-1β levels. Moreover, the treatment decreased the reduction in urinary creatinine, urinary urea, ratios of urinary creatinine to serum creatinine and urinary urea to serum urea, Fex Urea and Bcl-2 expression in kidney. In conclusion, although Pleurotus ostreatus and Agaricus bisporus extracts and carvedilol all significantly inhibited the progression of nephrolithiasis and showed nephroprotective effects against ethylene glycol-induced kidney dysfunction, Pleurotus ostreatus and Agaricus bisporus seemed to be more effective than carvedilol. Moreover, the nephroprotective effects may be mediated via affecting NF-κB activation, extrinsic apoptosis and intrinsic apoptosis pathways.

Highlights

Urolithiasis is a urinary stone disease involving the calcifications in the kidney [1]
The two tested mushrooms P. ostreatus and A. bisporus were subjected to preliminary phytochemical screening and Gas Chromatography–Mass Spectrometry (GC-Mass Spectrometry (MS)) analysis of their aqueous extracts
Gas Chromatography (GC)-MS of A. bisporus extract revealed the presence of multiple antioxidant and anti-inflammatory abundant constituents and chemical groups including N-methoxy-methanamine, [66], 2-pyrrolidinone [70,71] and fumaric acid, 2-heptyl octyl ester [72,73,74,75]

Summary

Introduction

Urolithiasis is a urinary stone disease involving the calcifications in the kidney [1]. Urolithiasis is a very painful and the third common disorder of urinary system [2,3]. Epidemiological studies have revealed that the majority of stones are commonly composed of calcium oxalate (CaOx) [4,5]. The risk of developing urolithiasis appears to be associated with a multitude of genetic, physiological and nutritional disorders, ranging from general hyperoxaluria to obesity [6]. Hyperoxaluria describes the occurrence of high oxalate concentrations in urine. Hyperoxaluria is, in turn, an important risk factor for urolithiasis and more than 80% of the uroliths consist of CaOx, either alone or mixed with calcium phosphate [12,13,14]

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