Protective effects of penehyclidine hydrochloride on septic mice and its mechanism.
Anticholinergics can have protective effects against septic shock. Penehyclidine hydrochloride (PHC) is a novel anticholinergic agent exhibiting few cardiovascular side effects. This work explored the protective effects of PHC on septic mice and its mechanism. Mice were randomly divided into four groups: sham control, cecal ligation and puncture (CLP), CLP/0.3 mg/kg PHC, and CLP/0.45 mg/kg PHC, with 10 mice in each. One hour before surgery, PHC-treated mice received an intraperitoneal injection of PHC and an equal volume of saline in the other two groups. Blood plasma and tissue samples were collected at 12 h after surgery. Serum TNF-alpha, histopathology, superoxide dismutase (SOD), malondialdehyde (MDA), and expression of iNOS in lung and hepatic tissues were examined. Another 40 mice were randomly assigned to four equal groups to observe survival status during 96 h after operation. Treatment of 0.45 mg/kg PHC markedly decreased TNF-alpha, MDA content, and iNOS mRNA expression, and enhanced SOD activity (P < 0.05 and P < 0.01). Treatment of 0.45 mg/kg PHC might have a protective effect against sepsis. Its action mechanisms are probably involved in the inhibition of inflammatory factor production and suppression of iNOS mRNA expression and lipidperoxidation.
Zhan
Jia
J
Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
Wang
Yanlin
Y
Wang
Chengyao
C
Li
Jianguo
J
Zhang
Zongze
Z
Jia
Baohui
B
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008315:Malondialdehyde / Q000097:blood; D051379:Mice; D046529:Microscopy, Electron, Transmission; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011812:Quinuclidines / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D018805:Sepsis / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000097:blood; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D011812:Quinuclidines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C486140:penehyclidine; D008315:Malondialdehyde; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase