Abstract：
:Milacemide (2-n-pentylaminoacetamide) hydrochloride was administered by continuous i.v. infusion for up to 7 days, at 300 and 600 mg/kg per day to male Sprague-Dawley rats. This was intended to provide high and sustained exposure to evaluate the effect of a preterminal 24-h fast on liver lipid content. Liver lipid content, as assessed by triglyceride concentration and histopathology, was not different in saline controls or rats infused with up to 600 mg/kg per day for up to 7 days, when they had access to food up to sacrifice. When the rats were fasted for 24 h before sacrifice, milacemide produced microsteatosis in the periportal and midzonal areas. The effect was significant after 2 days of infusion at 600 mg/kg per day and increased in intensity with duration of administration. After 7 days of infusion, at 600 mg/kg per day, liver triglycerides increased by more than 4-fold in rats fasted for the last 24 h. No other differences from the controls were observed at light microscopy or in liver protein content and AST activity. Liver ALT activity was decreased by 28% and plasma ALT activity by 23%. Plasma triglyceride levels were lowered by milacemide, in both fasted and fed rats. This study demonstrates that fasting for 24 h triggers the development of liver microsteatosis in rats exposed to milacemide. Fasting has been previously described to increase liver microsteatosis after administration of sodium valproate, 4-en valproate and pentenoic acid in the rat. These findings might help to identify the mechanism of the hepatic effects of milacemide.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Rakotoamboa JL,Masson M,Palate B,Carleer J,Roba Jdoi
10.1007/s002040050067subject
Has Abstractpub_date
1994-01-01 00:00:00pages
266-71issue
4eissn
0340-5761issn
1432-0738journal_volume
68pub_type
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