Involvement of lipid peroxidation in free fatty acid-induced isolated rat pancreatic acinar cell injury.
It was reported that free fatty acids degraded from triglycerides by lipase may play a major role in acute necrotizing or hyperlipidemia-induced pancreatitis. We hypothesized that this injury may be related to the peroxidation of cell membrane phospholipids and tested this hypothesis using isolated pancreatic acini. Pancreatic acini were prepared from male Sprague-Dawley rats by collagenase digestion. Linoleic acid was added (0.1-1.0 mM) to the acinar cell suspension to induce cell injury. Acinar cell damage was measured by lactate dehydrogenase release and by trypan blue exclusion. Phosphatidylcholine hydroperoxide and alpha-tocopherol in the acinar cells were measured. Protective effects of alpha-tocopherol (0.5, 5.0 mM) against this type of cell injury were also evaluated. When isolated acinar cells were treated with linoleic acid, a significant decrease in viability was observed in a time- and dose-dependent manner. In addition, the levels of phosphatidylcholine hydroperoxide after treatment of 0.5 mM of linoleic acid were increased and levels of alpha-tocopherol were decreased significantly. alpha-Tocopherol significantly ameliorated both cellular injury (p < 0.01) and increases in phosphatidylcholine hydroperoxide (p < 0.01). These data suggest that lipid peroxidation of the cellular membrane is an important component of the pancreatic cell injury mediated by free fatty acids.
Morita
Y
Y
First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
Yoshikawa
T
T
Takeda
S
S
Matsuyama
K
K
Takahashi
S
S
Yoshida
N
N
Clemens
M G
MG
Kondo
M
M
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019787:Linoleic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008163:Luminescent Measurements; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010195:Pancreatitis / Q000209:etiology; D010713:Phosphatidylcholines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000378:metabolism / Q000494:pharmacology
D010713:Phosphatidylcholines; C057590:phosphatidylcholine hydroperoxide; D014810:Vitamin E; D019787:Linoleic Acid; D007770:L-Lactate Dehydrogenase