Scavenging Effects of Hydroxycinnamic acids on Paraquat Induced Hepatotoxicity (II)

Paraquat 유도 간독성에 대한 Hydroxycinnamic acid계 화합물의 독성 경감 효과 (II)

  • 최병기 (동덕여자대학교 약학대학) ;
  • 오은정 (동덕여자대학교 약학대학)
  • Published : 1999.10.01

Abstract

Antioxidative and scavenging effects were investigated by using two hyaroxycinnamic acids (caffeetannins). such as caffeic acid and chlorogenic acid, on oxidative stress and hepatotoxicity that induced by paraquat. The results are summerized as follows: 1. To assess radical scavenging ability, reduction concentration (IC$\sub$50/) of 1.1 diphenyl-2-dipicrylhydrazine (DPPH) were measured. IC$\sub$50/ values of caffeic acid and chlorogenic acid were 29.7 ${\pm}$0.6 ${\mu}$M and 26.0${\pm}$0.5 ${\mu}$M respectively. Their radical scavenging activities showed concentration-dependent manner. 2. In H$_2$O$_2$-induced hemolysis assay to rat blood, caffeic acid and chlorogenic acid led to different effects, whose hemolysis inhibition ratios at 100 ${\mu}$M were 45.2${\pm}$7.1% and 11.6${\pm}$3.1% respectively 3. In hypoxanthine-xanthine oxidase system producing superoxide anion, caffeic acid and chlorogenic acid showed different inhibitory activities of xanthine oxidase showing 36.8${\pm}$4.3% and 5.4${\pm}$2.3% respectively. 4. To microsomal NADPH dependent cytochrome p-450 reductase in rat liver, paraquat consumed NADPH at a dose-dependent manner from 0 to 1 ${\mu}$M paraquat concentration. Caffeic acid and chlorogenic acid blocked NADPH consumption rates at concentration-dependent manner and inhibition ratios at 100 ${\mu}$M were 67.6% and 59.2% respectively. 5. Administration (30mg/kg, iv) of paraquat to rats caused the marked elevation of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and lipid peroxides (LPO) in the serum and lipid peroxides in the microsome as compared to the control group. Serum GOT, GPT, LDH, ALP and LPO and liver microsomal LPO were reduced significantly by caffeic acid (50mg/kg), chlorogenic acid (25mg/kg) and silymarin (150 mg/kg) as compared to the paraquat group. From these results, caffeic acid and chlorogenic acid exerted their antioxidative agents by removing reactive oxygen substance (ROS) and scavenging effects by inhibiting ROS generating enzyme. As a general, two hydroxyeinnamic acids showed the useful compounds for scavenger and reducer on the paraquat induced hepatotoxicity.

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