Fisetin, a dietary flavonoid, attenuates hyperammonemia and improves circadian locomotor deficits, redox balance, and astrocytic markers in rats

• Protective influence of fisetin (dietary flavonoid) on hyperammonemia was studied.
• Hyperammonemic rats showed raised oxidative stress and glutamate level in brain.
• Downregulated astrocytic markers were seen under hyperammonemia.
• Fisetin assuages these effects by antioxidant and cytoprotective actions.

Fisetin, a bioactive flavonoid, found in many fruits, was administered orally (50 mg/kg body weight) to hyperammonemic rats (treated with ammonium chloride (AC) for 8 weeks (i.p. injections, 100 mg/kg body weight). Treatment with AC augmented oxidative stress, levels of ammonia, enzymes (alanine and aspartate transaminases and alkaline phosphatase) in blood, glutamate and glutamine content in brain, caused disturbances in the circadian locomotor rhythm with a reduction in amplitude and period and downregulated the expression of soluble guanylyl cyclase (sGC) and glial fibrillary acidic protein (GFAP) in brain. Co-treatment of fisetin treatment with AC, prevented the AC-induced elevation in oxidative stress, normalized the levels of ammonia, transaminases and alkaline phosphatase in circulation, glutamate and glutamine in brain, upregulated the expression of sGC and GFAP and stabilized the circadian locomotor rhythm. Thus, fisetin assuages AC induced effects through its antioxidant, anti-inflammatory, cytoprotective, neuroprotective and neurotrophic properties.