chrysin and 3-nitropropionic-acid

3-Nitropropionic acid (3-NP) is an irreversible inhibitor of mitochondrial complex-II that causes transcriptional dysregulation, bioenergetics failure, protein aggregation and oxidative damage similar to Huntington's disease (HD) pathogenesis. Chrysin, a bioactive flavonoid reported to have anti-inflammation, antioxidant, vasorelaxant and neuroprotective property. The present study was framed to determine the neuroprotective efficiency of chrysin upon 3-NP induced oxidative stress, mitochondrial dysfunctions and neurodegeneration. 3-NP (10mg/kg b.w. i.p.) administration for 14days exhibited significant (P<0.01) behavioral alterations, mitochondrial dysfunction and oxidative damages to biomolecules, finally causes cell death. Chrysin at 50mg/kg b.w. orally for 14days improved all the behavioral performances and regulated the complex activities in mitochondria. Further, chrysin diminished the oxidative stress markers (lipid peroxidation, nitrite and protein carbonyls) by significantly (P<0.01) improving the antioxidant status (superoxide dismutase, catalase and reduced glutathione) in striatal mitochondria. Indeed, chrysin prevents apoptosis by upregulating the Bcl-2 mRNA expression and downregulating the pro-apoptotic (Bax, Bad) mRNAs in 3-NP induced condition. Furthermore, the survival of striatal neurons against 3-NP toxicity was enhanced upon chrysin treatment which was evidenced by observing histopathological studies. Hence, the present study collectively suggests that the chrysin can serve as a potential therapeutic agent on 3-NP induced mitochondrial deficits and subsequent apoptosis.

Topics: Animals; Apoptosis; Basal Ganglia; bcl-2-Associated X Protein; bcl-Associated Death Protein; Behavior, Animal; Biomarkers; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Flavonoids; Huntington Disease; Male; Maze Learning; Mitochondrial Diseases; Mitochondrial Swelling; Motor Activity; Nerve Degeneration; Neuroprotective Agents; Nitro Compounds; Oxidative Stress; Postural Balance; Propionates; Proto-Oncogene Proteins c-bcl-2; Rats, Wistar; Signal Transduction; Time Factors; Up-Regulation