基于N-乙酰转移酶研究槲皮素对大鼠体内异烟肼代谢的影响

目的 基于N-乙酰转移酶(NAT)的表达及活性检测,研究槲皮素对大鼠体内异烟肼(INH)代谢及药动学特征影响.方法 雄性Wistar大鼠单独灌胃给予INH(60 mg/kg)或槲皮素(50 mg/kg)联合INH(60 mg/kg).分别于给药后不同时间收集血清,应用液质联用技术测定血清中INH及其代谢物乙酰异烟肼(A...

Effects of Quercetin on Rat Isoniazide Metabolism via N-acetyltransferase Evaluation

Objective To investigate the effect of quercetin on the metabolic properties of isoniazide(INH)in rats by evaluating N-acetyltransferase(NAT).Methods Male Wistar rats were orally administered with INH(60 mg/kg)alone or in combination with quercetin(50 mg/kg).Serum samples were collected at the designated time points after INH administration.The serum concentrations of INH and its metabolite acetylisoniazid(Ac-INH)were determined using HPLC-MS,and the pharmacokinetic parameters were calculated.After that,liver samples were collected to determine the protein expression and enzyme activity of NAT in order to explore the underlying mechanism.Results Compared to the INH treated group,quercetin and INH co-administration significantly elevated the serum concentration of INH(P<0.05)L/h/kg,accompanied by markedly reduced concentration of Ac-INH(P<0.05).The pharmacokinetic parameters of AUC0→t(60.15±9.69 vs 43.40±2.89)mg h/L and t1/2(3.09±1.56 vs 1.07±0.13)h in quercetin pretreated rats were all significantly increased,while those of CL/F were markedly reduced(0.93±0.15 vs 1.38±0.11,P<0.05).Moreover,compared to the INH treated group,NAT activity rather than NAT expression in the quercetin and INH co-administration group was markedly reduced(P<0.05).Conclusion Quercetin can reduce the metabolism of INH and the concentration of Ac-INH by inhibiting NAT activity.This finding may provide an important clue to the prevention of INHinduced hepatotoxicity.