Pleurotus ostreatus opposes mitochondrial dysfunction and oxidative stress in acetaminophen-induced hepato-renal injury

Abstract

BackgroundAcetaminophen (APAP)-induced toxicity is a predominant cause of acute hepatic and renal failure. In both humans and rodents toxicity begins with a reactive metabolite that binds to proteins. This leads to mitochondrial dysfunction and nuclear DNA fragmentation resulting in necrotic cell death. Pleurotus ostreatus (an edible oyster mushroom) is well recognized as a flavourful food, as well as a medicinal supplement. In the present study, we evaluated the role of Pleurotus ostreatus in the protection against APAP-induced hepato-renal toxicity. We also explored the mechanism by which Pleurotus ostreatus exerts its effects.MethodsNinety adult male Swiss albino mice were divided into three groups (30 mice/group). Mice were offered normal diet (control and APAP groups), or diet supplemented with 10% Pleurotus ostreatus (APAP + Pleurotus ostreatus) for 10 days. Mice were either treated with vehicle (control group, single intra-peritoneal injection.), or APAP (APAP and APAP + Pleurotus ostreatus groups, single intra-peritoneal injection, 500 mg/kg), 24 hours after the last meal.ResultsAPAP increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) glutamate dehydrogenase (GDH), creatinine, blood urea nitrogen (BUN), urinary kidney injury molecule-1 (KIM-1), and hepatic and renal malondialdehyde (MDA) content. APAP decreased hepatic and renal glutathione (GSH) content, as well as glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities. Supplementation with Pleurotus ostreatus significantly reduced APAP-induced elevated levels of ALT, AST, GDH, creatinine, BUN, KIM-1and MDA, while GSH level, and GSH-Px and SOD activities were significantly increased. Our findings were further validated by histopathology; treatment with Pleurotus ostreatus significantly decreased APAP-induced cell necrosis in liver and kidney tissues.ConclusionsWe report here that the antioxidant effect of Pleurotus ostreatus opposes mitochondrial dysfunction and oxidative stress accompanying APAP over-dose, with subsequent clinically beneficial effects on liver and kidney tissues.

Ameliorative effect of naringin in acetaminophen-induced hepatic and renal toxicity in laboratory rats: role of FXR and KIM-1

“…[60][61][62] Several lines of studies suggested that free radical scavenging enzymes, i.e., SOD and GSH decreased and MDA, a lipid peroxidation end product increased when administered with APAP. 11 In line with previous studies 63,64 the present study also found significantly decreased SOD and GSH levels as well as increased MDA level during APAP treatment in the hepatic and renal tissue. Naringin treatment significantly enhanced tissue SOD and GSH as well as decreased MDA levels, demonstrating that naringin could maintain the abnormal antioxidant and ROS generation, which in turn modulate the membrane integrity against the APAPinduced cellular injury.…”

“…[89][90][91] Recently, in a mice model it has been shown that APAP-induced renal toxicity increases KIM-1 expression. 11 Similarly, in our study, we also observed significantly increased KIM-1 expression in APAPinduced renal toxicity. The exact mechanism behind the enhanced KIM-1 expression in APAP-induced renal toxicity is still not elucidated, but from our histopathological investigation, we can conclude that elevated KIM-1 expression in the renal tissue could be due to oxidative stress followed by necrotic cell death.…”

“…9,10 The equilibrium between ROS generation and the non-enzymatic antioxidant (GSH), superoxide dismutase (SOD), catalase (CAT) notion of being important for the APAP-induced toxicity. 5,11 Farnesoid X receptor (FXR) or NR1H4 is a nuclear receptor transcript or factor play a vital role in the regulation of bile acids, cholesterol, glucose metabolism, and lipoproteins. It has been reported that FXR activation could be beneficial in the APAP-induced hepatic toxicity.…”

Effects of Long Non-Coding RNA LINC00963 on Renal Interstitial Fibrosis and Oxidative Stress of Rats with Chronic Renal Failure via the Foxo Signaling Pathway

“…The overexpression of oxidative processes is involved in CRF patients and remains the significant factors for elevated morbidity and mortality in these patients [29]. Another research has showed that the balance between the production of reactive oxygen species (ROS) and the availability of antioxidant enzymes, such as SOD, BUN, MDA and GSH-Px, is consequently critical for avoiding the tissue damage induced by OS [30, 31]. GSH-Px, as one of the markers of oxidative stress, is highly expressed in RIF rats [32].…”

Protective effect of ivy leaf extract on paracetamol-induced oxidative stress and nephrotoxicity in mice

“…The mechanism of acetaminophen-induced nephrotoxicity and hepatotoxicity has been reported by other investigators and showed that paracetamol causes oxidative stress and renal toxicity when used at high doses (21)(22)(23)(24)(25)(26).…”