Caffeic acid phenethyl ester reduces mortality and sepsis-induced lung injury in rats.
OBJECTIVE
Sepsis and ensuing multiorgan failure continue to be the major causes of mortality in intensive care units. Nuclear factor (NF)-kappaB activation is supposed to be one of the targets in the treatment of sepsis. We studied the effectiveness of caffeic phenethyl ester (CAPE), a known NF-kappaB inhibitor, in cecal ligation and puncture (CLP)-induced sepsis and lung injury.


METHODS
Randomized, controlled animal study.


METHODS
Research laboratory of an academic institution.


METHODS
Female Sprague-Dawley rats.


METHODS
CLP was performed in all rats except the rats in control and sham+CAPE groups. CAPE was administered to rats at the time of operation in sham+CAPE and CAPE+sepsis 0 groups. CAPE was administered to rats in the CAPE+sepsis12 group 12 hrs after CLP. Eight rats from each group were killed 24 hrs after CLP. Blood was taken for assessment of interleukin-1, interleukin-6, interleukin-10, and tumor necrosis factor-alpha; the right lung was removed for histopathologic examination and the left lung for biochemical examination. Apoptosis, inducible nitric oxide synthase, heat shock protein 70, malondialdehyde, catalase, superoxide dismutase, and glutathione peroxidase were studied. The rest of the rats were observed for mortality.


RESULTS
Mortality was significantly decreased in groups that received CAPE compared with the sepsis group. All cytokine levels were similar to control levels only in the CAPE+sepsis12 group. Apoptosis, inducible nitric oxide synthase, and heat shock protein 70 evaluation were significantly changed between all groups in the following order: control < sham+CAPE< CAPE+sepsis12 < CAPE+sepsis 0 < sepsis. Malondialdehyde and catalase were increased in the sepsis group.


CONCLUSIONS
CAPE reduced mortality in sepsis and improved histopathologic variables best when it was administered after the onset of sepsis.
Fidan
Huseyin
H
Department of Anesthesiology, Faculty of Medicine, Afyon Kocatepe University, Afyon, Turkey. drhfidan@yahoo.com
Sahin
Onder
O
Yavuz
Yucel
Y
Kilbas
Aynur
A
Cetinkaya
Zafer
Z
Ela
Yuksel
Y
Ozen
Oguz Aslan
OA
Altuntas
Irfan
I
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002109:Caffeic Acids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000187:drug effects; D005260:Female; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010626:Phenylethyl Alcohol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000473:pathology / Q000517:prevention & control*; D018805:Sepsis / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis
D002109:Caffeic Acids; D016207:Cytokines; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol