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Effect of endotoxin pretreatment on hepatic stellate cell response to ethanol and acetaldehyde
Author(s) -
Quiroz Silvia C,
Bucio Leticia,
Souza Verónica,
Hernández Elizabeth,
González Elvira,
GÓmezQuiroz Luis,
Kershenobich David,
VargasVorackova Florencia,
GutiérrezRuiz MA. Concepción
Publication year - 2001
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1046/j.1440-1746.2001.02619.x
Subject(s) - acetaldehyde , lipopolysaccharide , ethanol , lipid peroxidation , glutathione , hepatic stellate cell , endocrinology , medicine , tumor necrosis factor alpha , biochemistry , chemistry , oxidative stress , enzyme
Background and Aim: The role of endotoxin in alcohol‐induced liver damage is well recognized. How pre‐exposure to endotoxin might affect alcohol injury is not known. We herein studied the effect of endotoxin pretreatment on hepatic stellate cell (HSC) response to ethanol and acetaldehyde. Methods: Rat HSC (CFSC‐2G) were exposed to media supplemented with 1 μg/mL lipopolysaccharide (LPS). This was followed by a 24 h exposure to media containing LPS plus 50 mmol/L ethanol or 175 μmol/L acetaldehyde. Lipid peroxidation, collagen, and tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6 and transforming growth factor (TGF)‐β 1 secretion were determined at the end of both periods of exposure. Results: Lipopolysaccharide pretreatment did not modify lipid peroxidation induced by ethanol or acetaldehyde alone. Glutathione (GSH) content decreased to 4.2 ± 0.5 and 16.3 ± 0.8 nmol protein after exposure to ethanol or acetaldehyde alone, and decreased further with LPS pretreatment (2.4 ± 0.2 and 2.7 ± 0.3 nmol/mg protein, respectively). Oxidized GSH (GSSG) content increased in ethanol and acetaldehyde LPS‐pretreated cells only. Collagen secretion increased to 988 ± 82 and 1169 ± 91 μg/10 6 cells after exposure to acetaldehyde or LPS alone. Lipopolysaccharide pretreatment enhanced collagen secretion significantly in both ethanol‐ and acetaldehyde‐treated cells (969 ± 56 and 1360 ± 72 μg/10 6 cells, respectively). Interleukin‐6 production increased to 288 ± 48, 1195 ± 86 and 247 ± 35 pg/mL per 10 6 cells after ethanol, acetaldehyde and LPS exposure, and increased further with LPS pretreatment in ethanol‐exposed cells (680 ± 23 pg/mL 10 6 cells). Conclusion: Lipopolysaccharide pretreatment of HSC adds to the damage produced by ethanol and acetaldehyde by diminishing GSH content and increasing GSSG content, collagen and IL‐6 secretion.