Effects of chondroitin sulfate on alteration of actin cytoskeleton in rats with acute necrotizing pancreatitis.
BACKGROUND
In experimental acute pancreatitis, a large amount of reactive oxygen species are produced, and in turn cytoskeletal changes may be induced in pancreatic tissue. These changes contribute to an imbalance of digestive enzyme segregation, transport, exocytosis and activation, resulting in cell injury. In this study, we assessed the effects of chondroitin sulfate (CS) on attenuation of oxidative damage and protection of F-actin in rats with acute necrotizing pancreatitis (ANP).


METHODS
Ninety male Wistar rats were divided randomly into three groups. Group A was infused with 5% sodium taurocholate; group B was treated with CS; and group C served as control. Rats from the three groups were killed at 1, 3 or 8 hours. The levels were measured of malonyl dialdehyde (MDA), total superoxide dismutase (SOD), glutathione synthetase (GSH), serum amylase (SAM) and adenosine triphosphate (ATP). F-actin immunostained with rhodamine-phalloidin was analyzed using a confocal laser scanning system and the content of F-actin protein was determined.


RESULTS
The levels of SAM increased in groups A and B, whereas the levels of GSH, SOD and ATP in group A decreased markedly during pancreatitis, and MDA increased significantly. The levels of GSH, SOD and ATP in group B were higher than those in group A, but the level of MDA was lower than in group A. At the same time, ANP resulted in early disruption of the cytoskeleton with dramatic changes and a loss of F-actin. Administration of CS moderated the damage to the actin cytoskeleton.


CONCLUSIONS
Retrograde infusion of sodium taurocholate via the pancreatic duct may produce pancreatic necrosis and a marked increase in serum amylase activity, induce a severe depletion of ATP level, prime lipid peroxidation, and damage F-actin. Treatment with CS can ameliorate pancreatic cell conditions, limit cell membrane peroxidation, protect F-actin, and attenuate pancreatitis.
He
Zhong-Ye
ZY
Department of General Surgery, First Affiliated Hospital, China Medical University, Shenyang 110001, China.
Guo
Ren-Xuan
RX
D000199:Actins / Q000187:drug effects / Q000378:metabolism*; D000681:Amylases / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000627:therapeutic use*; D003124:Colorimetry; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018613:Microscopy, Confocal; D019283:Pancreatitis, Acute Necrotizing / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
D000199:Actins; D000975:Antioxidants; D008315:Malondialdehyde; D002809:Chondroitin Sulfates; D000681:Amylases