Abstract
Ammonia is a key neurotoxin involved in the neurological complications of the liver. Elevated ammonia leads to hyperammonemic condition which affects several important central nervous system functions. Fisetin is one of the naturally occurring flavonoids found in fruits and vegetables; it exhibits a wide variety of therapeutic benefits such as anticancer, antidiabetic, antioxidant, antiangiogenic, and neuroprotective effects. In this present study, chronotherapeutic efficacy of fisetin on ammonium chloride (AC)-induced hyperammonemic rats was aimed to establish the maximum drug effect by determining the best fitting biological time for drug dosing that helps to increase the therapeutic index of fisetin. The antihyperammonemic effect of fisetin was determined by administering (50 mg/kg b.w. oral) to rats at 06:00, 12:00, 18:00 and 24:00 h against AC (100 mg/kg b.w. i.p.) induced hyperammonemic Wistar rats (180-200 g). Amelioration of pathophysiological conditions of AC-induced hyperammonemia rats by fisetin at different time points (06:00, 12:00, 18:00 and 24:00 h) were measured by assessing the circulatory levels of ammonia, urea, uric acid, creatinine, bilirubin, and liver marker enzymes. Fisetin administration at 24:00 h showed more significant effects on those parameters than the other time points (p<0.05) and this might be due to pharmacokinetic property of the drug (fisetin) on temporal variations.
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