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

doi:10.19803/j.1672-8629.2021.02.05

Abstract

Abstract: 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 AUC_0→t (60.15±9.69 vs 43.40±2.89)mg h/L and t_1/2 (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 INH-induced hepatotoxicity.

Key words: isoniazide, quercetin, N-acetyltransferase, pharmacokinetics

CLC Number:

R965

RAO Zhi, ZANG Kaihong, WANG Xiaohua, QIN Hongyan. Effects of Quercetin on Rat Isoniazide Metabolism via N-acetyltransferase Evaluation[J]. Chinese Journal of Pharmacovigilance, 2021, 18(2): 121-125.

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