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Hesperidin과 Hesperetin의 AAPH로 산화적 손상을 유도한 동물 모델에서 항산화 활성 조절을 통한 신장 보호 효과

Protective Effects of Hesperidin and Hesperetin on Kidney Toxicity by Regulation of Antioxidant Activity in AAPH-induced Rats

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초록

본 연구는 hesperidin과 hesperidin의 aglycone 형태인 hesperetin의 2,2'-azobis (2-aminopropane) dihydrochloride (AAPH)에 의해 신장독성이 유도된 쥐에서 신장 보호 효과에 대해 연구하였다. Hesperidin과 hesperetin은 200 mg/kg/day의 농도로 7일간 위내투여하였으며, AAPH를복강주사하여 급성 신장 손상을 유도하였다. 이 후 쥐의 신장 조직에서 지질과산화 함량, nitric oxide (NO) 생성량, catalase 효소 활성을 측정하였으며, nuclear factor-kappa B (NF-κB) 및 inducible nitric oxide synthase (iNOS) 단백질 발현량을 측정하였다. AAPH로 신장 독성을 유도한control군의 신장 내 지질과산화 및 NO 생성량은 신장 독성을 유도하지 않은 normal군에 비해 유의적으로 증가하여 산화적 손상이 유도됨을확인하였다. 반면 hesperidin과 hesperetin를 투여했을 때 신장 내 지질과산화 및 NO 생성량이 control군에 비해 유의적으로 감소하여 산화적스트레스 개선 효과를 확인하였다. Hesperidin과 hesperetin을 투여한 군의 경우 신장 내 항산화 효소인 catalase 활성을 유의적으로 증가시켰다. 뿐만 아니라, hesperidin과 hesperetin의 투여는 AAPH로 신장독성을 유도한 control군 100% 대비 NF-κB 단백질을 각각 66% 및 71%로, iNOS 단백질 발현을 각각 46% 및 33%로 억제시켰다. 따라서 본 연구를 통해 hesperidin과 hesperetin의 투여가 항산화 활성 조절을 통해 AAPH로유도된 신장 독성을 억제하는 것을 알 수 있었다.

Abstract

The purpose of this study is the protective effect of hesperidin and its aglycone, hesperetin, against kidney toxicity induced by 2,2'-azobis (2-aminopropane) dihydrochloride (AAPH) in rats. The hesperidin and hesperetin at a dose of 200 mg/kg/day were orally administered for 7 days in the rats and acute injuries were induced by intraperitoneal injection with AAPH. After then, we measured lipid peroxidation, nitric oxide production, catalase activity, and protein expressions in the kidney of rats. Treatment of AAPH in rats significantly increased lipid peroxidation and nitric oxide (NO) production in the kidney compared with the AAPH-non-treated normal group. However, administration of hesperidin and hesperetin significantly decreased lipid peroxidation and nitric oxide (NO) production in AAPH-induced rats. In addition, hesperidin and hesperetin-administered rats significantly increased catalase activity in the kidney compared with the AAPH-induced control group. Furthermore, administrations of hesperidin and hesperetin significantly were down-regulated protein expressions of nuclear factor-kappa B by 66% and 71%, respectively, and expressions of inducible nitric oxide synthase by 46% and 33%, respectively, compared to 100% of control group. Therefore, this study demonstrated that administration of hesperidin and hesperetin led to a reduction of AAPH-induced kidney toxicity by regulation of antioxidant activity.

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