Journal of the Korean Pediatric Society 1999;42(7):966-979.
Published online July 15, 1999.
Changes in GFAP Immunoreactivity of Astrocytes in Rats with Reye's Syndrome Induced by Valproic Acid and the Effects of Carnitine Supplementation
Young-Yoo Kim, Kyung-Tai Whang
Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea
Valproic Acid로 유발시킨 라이증후군 흰쥐에서 성상교세포 변화와 Carnitine 투여의 영향
김영유, 황경태
가톨릭대학교 의과대학 소아과학교실
Correspondence: 
Young-Yoo Kim, Email: 1
Abstract
Purpose
: This study was designed to investigate whether valproic acid(VPA) induces Reye's syndrome by analyzing blood chemistry, carnitine(CARN) concentration, and the morphologic changes of hepatocytes. The changes of GFAP immunoreactivity of astrocytes were examined in rats with Reye's syndrome induced by VPA. And the effects of CARN supplementation on Reye's syndrome were also investigated.
Methods
: Ten rats were assigned to each of the following 3 groups : control group(0.5ml of normal saline), VPA group(250mg/kg of VPA), and VPA plus CARN group(250mg/kg of VPA and 100mg/kg of CARN). Each dose was injected intraperitoneally every 12 hours for 7 days. All rats fasted overnight following the final injection.
Results
: In the VPA group, the levels of glucose and ketones decreased and the levels of ammonia, SGOT and lactates increased as compared with the control group. Lower levels of free CARN and higher acyl/free CARN ratios, indicating secondary CARN deficiency, were observed, and the appearance of transformed mitochondria of hepatocytes provided further evidence of mitochondrial metabolic dysfunction in Reye's syndrome. The GFAP immunoreactivity and the area percent of GFAP-positive astrocytes in the cingulum decreased in VPA group. In the VPA plus CARN group, there were no significant differences with the control group in blood chemistry, acyl/free CARN ratios and morphology of hepatocytes. However, the GFAP immunoreativity and the percent of GFAP-positive astrocytes in the cingulum decreased as much as in the VPA group.
Conclusion
: It is suggested that CARN supplementation may prevent abnormal findings of blood chemistry, CARN deficiency and the morphologic changes of liver mitochondria due to VPA, but CARN may have little effect on GFAP immunoreactivity of astrocytes in rats with Reye's syndrome induced by VPA.
Key Words: Valproic acid, Reye's syndrome, GFAP immunoreactivity of astrocytes, Carnitine supplementation


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