Protective effect of 4-hydroxy-TEMPO, a low molecular weight superoxide dismutase mimic, on free radical toxicity in experimental pancreatitis |
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Authors: | Zbigniew ?ledziński Michal Wo?niak J?drzej Antosiewicz Emanuele Lezoche Massimo Familiari Enrico Bertoli Lucedio Greci Alessandro Brunelli Nino Mazera and Zdzis?aw Wajda |
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Institution: | (1) II Surgical Department, Medical University School of Gdańsk, Kieturakisa 1, Poland;(2) Academy of Physical Education, Gdańsk, Poland;(3) University of Ancona, Italy;(4) I.N.R.C.A. and Biancalana Mazera Foundation, Ancona, Italy |
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Abstract: | Summary Rats develop acute pancreatitis when infused iv for 3 h with cerulein (10 μg/kg/h). Autopsies of the pancreas seen by light
microscope show interstitial edema, acinar cells vacuolization, and leukocyte margination in pancreatic capillaries; under
electron microscope, severe damage concerning mitochondrial and zymogen granules structures are apparent. Particularly, swelling
of the mitochondria and disruption of mitochondrial cristae was observed as well as formation of large vacuoles arising from
zymogen granules and liposome fusion. A significant increase of lipid hydroperoxide level in the pancreatic tissue was observed.
The purpose of this study was to evaluate the effect of 4-hydroxy-TEMPO—a low-mol-wt superoxide dismutase mimic—in a rat cerulein
model of acute pancreatitis, with the expectation that free radical mediated hydroperoxide formation and tissue damage may
be reduced significantly. Twenty-one male Wistar rats were divided into three groups: Group 1 (n=5) served as a control and was infused iv for 3 h with physiologic saline; Group 2 (n=8) was infused iv for 3 h with cerulein 10 μg/kg/h; and Group 3 (n=8) infused iv both with cerulein and 4-hydroxy-TEMPO 22.6 mg/kg/h. Pancreatic tissue damage was quantified by measuring lipid
hydroperoxide (LOOH) level, the weight of the organ, and by light and electron microscopic examination. 4-hydroxy-TEMPO penetration
across cellular membrane barriers was quantified by ESR spectrometric measuremts of 4-hydroxy-TEMPO concentration in pancreatic
tissue samples and pancreatic juice as well. Administering 4-hydroxy-TEMPO to rats resulted in preventing both lipid hydroperoxide
formation and severe morphological damage. 4-hydroxy-TEMPO crossed cellular membrane barriers and was excreted to pancreatic
juice. Infusion of 4-hydroxy-TEMPO appears to prevent pancreatic injury caused by free radicals in experimental cerulein pancreatitis. |
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Keywords: | Experimental acute pancreatitis cerulein 4-hydroxy-TEMPO therapy free radicals lipid hydroperoxides |
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