The protective effects of carbachol on visceral ischemia-induced lipid peroxidation injury in rats with sepsis

Abstract

To investigate the effect of carbachol (CAR) on visceral perfusion and lipid oxidation injury in rats with sepsis. Sixty-four Sprague-Dawley (SD) rats received cecal ligation and puncture (CLP) surgery, and they were divided randomly into two groups: septic model group (CLP group, n=32) and septic model with CAR-treatment group (CAR group, n=32). CAR (10 microg/kg, CAR group) or normal saline (CLP group) was immediately injected into penial vein. Sixteen animals in each group were used to observe the mortality rates 12 hours and 24 hours after CLP, and the remaining rats for measurement of variables of blood and tissue. At the 18 hours after CLP, the mean arterial pressure (MAP), the blood flow (BF) of liver, kidney and jejunum, the plasma levels of alanine aminotransferase (ALT) and creatinine (Cr) were measured. Animals were sacrificed after the aforementioned determinations, and specimens of liver, kidney and jejunum were harvested for evaluation of malondialdehyde (MDA), xanthine oxidase (XOD), and assessment of tissue water content (ratio of dry to wet weight) of those organs . The activity of diamine oxidase (DAO) in jejunal tissue was detected. The mortality rates of 12 hours and 24 hours of CAR group were 25.0% (4/16)and 50.0% (8/16) respectively, all significantly lower than those of CLP group [37.5% (6/16) and 75%(12/16), both P<0.05]. CAR treatment did not result in significant statistical difference in the levels of MAP compared with CLP group at 18 hours after CLP (P>0.05), but led to significant increases in BF of CAR group in liver, kidney and jejunum compared with those of CLP group (all P<0.05). The levels of XOD and MDA, as well as the tissue water content were significantly lower in CAR group than CLP group in kidney and jejunum (all P<0.05). The parameters of organ function were significantly different in CAR group compared with CLP group [ALT: (64.3+/- 8.3) U/L vs. (81.5+/-7.9) U/L, Cr: (96.4+/-7.0) micromol/L vs. (117.1+/-6.7) micromol/L, DAO: (0.20+/- 0.04) U/L vs. (0.12+/-0.03) U/L, all P<0.05]. The results indicate that CAR promotes visceral perfusion, inhibits lipid peroxidation production and alleviates visceral edema and dysfunction in rats with sepsis.