Neuroprotective effect of carnosine against salsolinol-induced Parkinson's disease

Abstract

Carnosine is a dipeptide of β-alanine and histidine amino acids. It is widely present in muscle and brain tissues. Carnosine has been demonstrated to be an antioxidant agent that is beneficial in animals. Reactive oxygen species (ROS) and aldehydes are are generated from membrane fatty acid oxidation. The antioxidant potential and toxicity of salsolinol had been extensively studied in vivo and in vitro. The present study analyzed the protective effect of carnosine against Parkinson's disease in the salsolinol-induced rat brain and rat brain endothelial cells. Antioxidant and biochemical markers were determined in vitro and in vivo. Histopathological examination was completed in order to evaluate the protective effect of carnosine on the cellular architecture of salsolinol-induced brain tissue. In order to confirm the protective effect of carnosine further, it was also investigated at an in vitro level using rat brain endothelial cells. Fluorescence and confocal studies indicated reduced apoptosis in the endothelial cells of the rat brain tissue. Antioxidant enzymes and lipid peroxidation levels were renormalized following treatment with carnosine. In addition, carnosine treatment reduced mitochondria-derived ROS in the rat brain endothelial cells. These findings suggest that carnosine may be a therapeutic agent against salsolinol-induced Parkinson's.

l-Homocarnosine, l-carnosine, and anserine attenuate brain oxidative damage in a pentylenetetrazole-induced epilepsy model of ovariectomized rats

“…l-Homocarnosine and l-carnosine were also shown to exert protective effects against DNA damage (Kang 2010), and carnosine supplementation was reported to protect rat brain endothelial cells by scavenging 4-hydroxynonenol and MDA. Moreover, l-carnosine exerted neuroprotective effects in Parkinson's disease (Zhao et al 2017), and both anserine and l-carnosine were shown to exert similar effects in an animal model of focal ischemia.…”

Not Just from Ethanol. Tetrahydroisoquinolinic (TIQ) Derivatives: from Neurotoxicity to Neuroprotection

“…6, panel a) and superoxide dismutase activity ( Fig. 6, panel b), was significantly reversed following treatment with carnosine, a dipeptide endowed with antioxidant properties (Zhao et al 2017). In addition, catalase activity in brain endothelial cells in salsolinol-treated rats was also significantly reduced (Zhao et al 2017) suggesting that salsolinol may also potentially damage proteins by producing cross-links (Libondi et al 1994;Zhao et al 2017).…”

“…Salsolinol's toxicity has been extensively studied in various in vitro (Yoshikawa 1993;von Bohlen und Halbach et al 2004;Olanow and Tatton 1999) and in vivo (Collins and Neafsey 2002) systems. In particular, in vivo and in vitro studies by Zhao et al (2017) reported that salsolinol could alter rat brain endothelial cells' morphology, but also determine apoptosis and necrosis (Table 1). This cytotoxicity, disclosed in salsolinol-treated rat brain endothelial cells by decreased glutathione content (Fig.…”

“…6, panel b), was significantly reversed following treatment with carnosine, a dipeptide endowed with antioxidant properties (Zhao et al 2017). In addition, catalase activity in brain endothelial cells in salsolinol-treated rats was also significantly reduced (Zhao et al 2017) suggesting that salsolinol may also potentially damage proteins by producing cross-links (Libondi et al 1994;Zhao et al 2017). Moreover, salsolinol has also been suggested to act as an endogenous neurotoxin, a molecule stable and difficult to clear out whose accumulation in SH-SY5Y cells may contribute to storage of toxins production of endogenous neurotoxins ( Fig.…”

Carnosine—a natural bioactive dipeptide: bioaccessibility, bioavailability and health benefits

“…The robust anti-oxidant, anti-excitotoxic, and mitochondria protecting activities of carnosine mainly rely on its protective effects against oxygen-glucose deprivation and against accumulation of reactive oxygen species (Bae et al, 2013). In a mice model of salsolinol-induced neurotoxicity, carnosine was shown to decrease the MDA and restore the activity of Glutathione(GSH), Superoxide dismutase (SOD) and catalase along with the reduced apoptosis and Reactive Oxygen Species (ROS) production, suggesting its therapeutic effect in salsolinol-induced Parkinson's disease (PD) (Zhao et al, 2017). In summary, an increasing number of studies have provided supportive evidence on the capacity of carnosine to restore or promote the activity of antioxidant enzymes, its ability to inhibit lipid oxidation together with its capacity to inhibit anti-crosslinking between amyloid-β and prion peptides, which altogether encourage the use of carnosine as a preventive and therapeutic approach against PD and AD.…”