The effect of carnosine pretreatment on oxidative stress and hepatotoxicity in binge ethanol administered rats

Abstract

<jats:p> Carnosine is a dipeptide having strong antioxidant effects. Oxidative stress plays an important role in pathogenesis of alcohol-induced liver injury. In this study, we investigated the effect of carnosine pretreatment on ethanol-induced oxidative stress and hepatotoxicity. Rats were given carnosine (2 g/L in drinking water) for 4 weeks and then ethanol was administered orally to rats at a dose of 5 g/kg every 12 hours for 3 doses totally (binge model). All rats were killed 6 hours after last ethanol injection. Plasma alanine (ALT) and aspartate (AST) transaminase activities and liver triglyceride, malondialdehyde (MDA), diene conjugate (DC), glutathione (GSH), vitamin E and vitamin C levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities were determined. Binge ethanol administration resulted in significant increases in plasma transaminase activities, hepatic triglyceride and lipid peroxide levels. However, GSH, vitamin E, vitamin C levels and GSH-Px and GST activities were found to be decreased following ethanol administration. Macromicrovesicular steatosis was also seen. Carnosine pretreatment appeared to prevent the increase of plasma ALT and AST activities and hepatic MDA and DC levels following ethanol treatment. In addition, hepatic GSH levels increased, but there were no changes in triglyceride, vitamin E, vitamin C levels and SOD, GSH-Px and GST activities, following ethanol treatment in carnosine-pretreated rats. There was also no change in liver histopathological appearance. In conclusion, carnosine prevented the increases in serum transaminase activities and lipid peroxides in liver of ethanol-treated rats, without any change on steatosis in liver. </jats:p>

Binge ethanol exposure increases the Krüppel-like factor 11-monoamine oxidase (MAO) pathway in rats: Examining the use of MAO inhibitors to prevent ethanol-induced brain injury

“…Moreover, neither binge ethanol nor MAOIs had any significant effect on the protein expression of SOD2 or catalase. Several studies have reported changes in expression/activity of SOD2 and catalase following ethanol exposure, while others have not (Carmiel-Haggai et al, 2003; Artun et al, 2010; Nogales et al, 2014). However, in the brain, catalase is largely responsible for the metabolism of ethanol to acetylaldehyde (Ledesma et al, 2014), which explains why we observed a group effect in binge ethanol-treated rats for increased catalase expression compared to control rats, regardless of MAOI administration.…”

“…Accumulation of ROS is also a critical mode of ethanol-induced cellular dysfunction (Ramachandran et al, 2003; Das and Vasudevan, 2007; Gonzalez et al, 2007; Boyadjieva and Sarkar, 2013). Oxidative stress is a devastating consequence of binge drinking and, thus, antioxidants provide substantial neuroprotection in models of binge ethanol exposure (Hamelink et al, 2005; Crews et al, 2006; Artun et al, 2010; Collins and Neafsey, 2012; Nair et al, 2015). Further, oxidative exposure of proteins due to ROS can modify their characteristics and function, such as enzymatic activity, binding of transcription factors, and increasing susceptibility to proteolytic degradation (Wolff and Dean, 1986; Davies, 1987; Davies et al, 1987).…”

The effects of carnosine in an experimental rat model of septic shock

“…Oxidative stress plays an important role in the pathogenesis of alcohol-induced liver injury. Research in ethanol-treated rats indicates that carnosine prevents increased serum transaminase and lipid peroxide activity in the liver without any change in steatosis [18]. The protective effects of carnosine and histidine against acetaminophen-induced hepatotoxicity were shown in another study [19].…”

Efficient gene delivery of primary human cells using peptide linked polyethylenimine polymer hybrid

“…L-carnosine acts as an antioxidant by scavenging hydroxyl radicals, binding divalent metals, upregulating enzymes that metabolize free radicals, and by promoting antiglycation [23, 24]. As a result, carnosine has been used as a protective agent in stroke models [25], liver injuries [26], and ophthalmologic disorders [27]. …”