Protective effects of a novel quinone derivative, (2E)-3-[5-(2,3 dimethoxy-6-methyl-1,4-benzoquinoyl)]-2-nonyl-2-propanoic acid on experimental alcoholic liver injury.
The present study evaluated the possible protective effect of ((2E)-3-[5-(2,3 dimethoxy-6-methyl-1,4-benzoquinoyl)]-2-nonyl-2-propanoic acid) (E3330), a newly synthesized hepatoprotective-quinone derivative, on experimental alcoholic liver injury. The intragastric feeding rat model for alcoholic liver disease was used. Eight sets of experiments were performed in which animals fed either corn oil and ethanol or corn oil, ethanol and E3330 were sacrificed at intervals of 1 week, 2 weeks, 1 month and 2 months. Nonparenchymal cell supernatant (NPCS) and plasma measurements of tumor necrosis factor, prostaglandin E2, leukotriene B4 and thromboxane B2 were evaluated in relation to the development of pathologic liver injury. Oral treatment with E3330 reduced the severity of liver injury; this was accompanied by a reduction in thromboxane B2 and leukotriene B4 levels in both NPCS and plasma and a reduction in tumor necrosis factor levels in NPCS. The difference in pathologic severity between drug- and nondrug-treated groups correlated well with the changes in the NPCS and plasma thromboxane B2/prostaglandin E2 ratio. These findings suggest that E3330 has multiple actions, such as inhibition of thromboxane, leukotriene and tumor necrosis factor generation, which contribute to its protective effect in alcoholic liver injury.
Department of Pathology, New England Deaconess Hospital, Boston, Massachusetts.
A A
AA
Nanji
S M
SM
Sadrzadeh
U
U
Khettry
P
P
Thomas
T
T
Yamanaka
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology*; D015232:Dinoprostone / Q000097:blood; D007975:Leukotriene B4 / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013929:Thromboxane B2 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016227:Benzoquinones; D011422:Propionates; D014409:Tumor Necrosis Factor-alpha; C075569:E 3330; D007975:Leukotriene B4; D013929:Thromboxane B2; D015232:Dinoprostone