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

Neurochemical Research
Krzysztof MilewskiMagdalena Zielińska

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 i...Continue Reading

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Citations

Oct 14, 2017·F1000Research·Victoria LiereSharon DeMorrow
Aug 6, 2019·Advanced Pharmaceutical Bulletin·Vahid GhanbarinejadReza Heidari
Jan 25, 2017·Molecular Neurobiology·Mariusz PopekMagdalena Zielińska
Nov 11, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Desheng CaiHaimin Lei
Nov 26, 2020·Journal of Experimental Pharmacology·Omid FarshadAkram Jamshidzadeh

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Methods Mentioned

BETA
Assay
Protein Assay

Software Mentioned

GeneTools
Prism

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