Effects of thalidomide and pentoxyphylline over local and remote organ injury after intestinal ischemia/reperfusion.
OBJECTIVE
We investigated the effects of thalidomide alone or in combination with pentoxyphylline upon intestinal ischemia/reperfusion (I/R) injury in the rat.


METHODS
Twenty male Wistar rats were randomized into 5 groups: sham-operated (SHAM), control (CTL), thalidomide (400 mg/kg) treatment (THAL), pentoxyphylline (50 mg/kg) treatment and a combination group (THAL + POX). I/R was induced by clamping the superior mesenteric artery for 45 minutes, followed by 120 minutes of reperfusion. We measured serum concentrations of aspartate-aminotransferase (AST), lactate dehydrogenase (LDH), tumor necrosis factor (TNF)-alpha as well as lipid peroxidation and antioxidant status. Intestinal samples were morphologically analyzed, and dry to wet (W/D) ratios calculated in intestinal, lung and liver samples, as a measurement of tissue edema.


RESULTS
Serum concentrations of AST, LDH, and TNF-alpha were increased after I/R in the CTL compared with the SHAM group (P < .05). Lipid peroxidation was also increased, and antioxidant capacity in serum, decreased (P < .05). The W/D ratio was elevated in all tissue samples as well (P < .05). Both thalidomide and pentoxyphylline effectively reduced AST, LDH, TNF-alpha, and lipid peroxidation levels, as well as attenuated tissue edema and intestinal injury induced by I/R (P < .05). Combination treatment showed only modest additive effects on lung W/D ratio and TNF-alpha levels.


CONCLUSIONS
Both drugs protected the intestine, lungs, and liver against intestinal I/R injury, probably by inhibition of TNF-alpha and lipid peroxidation. However, combination treatment showed small, additive effects.
Cámara-Lemarroy
C R
CR
Departamento de Fisiología, School of Medicine, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México. crcamara83@hotmail.com
Guzmán-de la Garza
F J
FJ
Alarcón-Galván
G
G
Cordero-Pérez
P
P
Muñoz-Espinosa
L E
LE
Fernández-Garza
N E
NE
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply* / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D008168:Lung / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D008297:Male; D010431:Pentoxifylline / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000097:blood* / Q000473:pathology / Q000517:prevention & control*; D013792:Thalidomide / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D010431:Pentoxifylline