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

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.

Naringin and Hesperidin Counteract Diclofenac‐Induced Hepatotoxicity in Male Wistar Rats via Their Antioxidant, Anti‐Inflammatory, and Antiapoptotic Activities

“…The previous histological lesions in diclofenac-injected rats may be attributed to the increase in the oxidative stress and excessive release of free radicals and ROS. This exacerbated production of ROS administration activates apoptosis through intrinsic pathway, aggravates cell necrosis through peroxidation of membrane lipids, and stimulates DNA breakages and mutations by oxidative damage [ 43 , 52 ] ( Figure 6 ). In addition to its necrotic effects, the elevation of TNF- α may augment hepatocyte apoptosis through linking to TNF receptor (TNFR) and death receptors leading to activation of extrinsic pathway of apoptosis [ 43 , 52 , 53 ] ( Figure 6 ).…”

“…This exacerbated production of ROS administration activates apoptosis through intrinsic pathway, aggravates cell necrosis through peroxidation of membrane lipids, and stimulates DNA breakages and mutations by oxidative damage [ 43 , 52 ] ( Figure 6 ). In addition to its necrotic effects, the elevation of TNF- α may augment hepatocyte apoptosis through linking to TNF receptor (TNFR) and death receptors leading to activation of extrinsic pathway of apoptosis [ 43 , 52 , 53 ] ( Figure 6 ). In turn, the improvement effects of naringin and hesperidin on liver histological lesions as well as ameliorations of serum biochemical parameters may be due to the suppressive effects of these two flavonoids on oxidative stress and enhancement of the antioxidant defense system in addition to the suppressive effects on inflammatory mediators such as TNF- α and IL-17 ( Figure 6 ).…”

Platelet-Rich Plasma Ameliorates Monosodium Iodoacetate-Induced Ankle Osteoarthritis in the Rat Model via Suppression of Inflammation and Oxidative Stress

“…The MIA injection to the rats provokes the increase in the inflammatory cytokines, while it suppresses the anti-inflammatory cytokines, thereby developing the inflammation process. In addition to the necrotic effects of TNF- α , it activates the tumor necrosis factor receptor or death receptors, thereby activating the extrinsic pathway of apoptosis ( Figure 13 ) [ 43 , 44 ]. Furthermore, the inflammatory environment and the increased levels of TNF- α and IL-17 could result in a decrease in the formation and release of growth factors (GFs) such as transforming growth factor (TGF) leading to reduced chondrogenesis and formation of chondrocytes from mesenchymal stem cells ( Figure 13 ) [ 45 ].…”

Medicinal Mushrooms: Bioactive Compounds, Use, and Clinical Trials

“…bisporus aqueous extracts on hyperoxaluria-induced urolithiasis induced in Wistar rats through the addition of 0.75% (v/v) ethylene glycol in drinking water for nine weeks have been investigated. The mushroom extracts inhibited the progression of nephrolithiasis and showed nephroprotective effects against ethylene glycol-induced kidney dysfunction [ 55 ].…”