Carnosine Reduces Oxidative Stress and Reverses Attenuation of Righting and Postural Reflexes in Rats with Thioacetamide-Induced Liver Failure

Abstract

Cerebral oxidative stress (OS) contributes to the pathogenesis of hepatic encephalopathy (HE). Existing evidence suggests that systemic administration of l-histidine (His) attenuates OS in brain of HE animal models, but the underlying mechanism is complex and not sufficiently understood. Here we tested the hypothesis that dipeptide carnosine (β-alanyl-l-histidine, Car) may be neuroprotective in thioacetamide (TAA)-induced liver failure in rats and that, being His metabolite, may mediate the well documented anti-OS activity of His. Amino acids [His or Car (100 mg/kg)] were administrated 2 h before TAA (i.p., 300 mg/kg 3× in 24 h intervals) injection into Sprague–Dawley rats. The animals were thus tested for: (i) brain prefrontal cortex and blood contents of Car and His, (ii) amount of reactive oxygen species (ROS), total antioxidant capacity (TAC), GSSG/GSH ratio and thioredoxin reductase (TRx) activity, and (iii) behavioral changes (several models were used, i.e. tests for reflexes, open field, grip test, Rotarod). Brain level of Car was reduced in TAA rats, and His administration significantly elevated Car levels in control and TAA rats. Car partly attenuated TAA-induced ROS production and reduced GSH/GSSG ratio, whereas the increase of TRx activity in TAA brain was not significantly modulated by Car. Further, Car improved TAA-affected behavioral functions in rats, as was shown by the tests of righting and postural reflexes. Collectively, the results support the hypothesis that (i) Car may be added to the list of neuroprotective compounds of therapeutic potential on HE and that (ii) Car mediates at least a portion of the OS-attenuating activity of His in the setting of TAA-induced liver failure.

Carnosine Mitigates Manganese Mitotoxicity in an In Vitro Model of Isolated Brain Mitochondria

“…22,23,26,55 It has been established that this peptide possesses antioxidant effects in different experimental models. 22,23,25,26,55,60 Carnosine also efficiently scavenges reactive end products of oxidative stress. 67 Hence, another important mechanism of protective properties of carnosine could be mediated through its antioxidant properties and decrease of mitochondria-born ROS (Figure 1).…”

Cortical Synaptic Transmission and Plasticity in Acute Liver Failure Are Decreased by Presynaptic Events

“…Neurological decline was determined in a group of mice ( n = 12) by measuring the corneal reflex, pinna reflex, vibrissae reflex, startle reflex, righting reflex, and postural reflex [ 16 , 19 ], with each given a score of 0 (no reflex evident), 1 (weak or delayed reflex), or 2 (regular reflex), resulting in a neurological score in the range of 0 to 12. The reflexes were measured every 2 h after AOM injection.…”

Transplantation of bone mesenchymal stem cells effectively promotes intestine regeneration to eliminate endotoxemia and reduce mortality in the animal model of acute liver failure

“…In this study, acute liver failure was induced by thioacetamide (TAA; Sigma-Aldrich, Bornem, Belgium) as previously described [14][15][16]. To get an ideal animal model, we divided the rats into groups to explore the best TAA dose and check point.…”