Gastroprotective Effect of L-Carnitine on Indomethacin
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- Category: Vol. 77, June 2009
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Gastroprotective Effect of L-Carnitine on Indomethacin-Induced Gastric Ulcer in Rats: The Involvement of Antioxidant Mechanisms and Nitric Oxide,ASHRAF K. BAHGAT
Abstract
This study investigated the gastroprotective effect of L-carnitine against indomethacin-induced gastric ulcer in rats and the possible mechanisms underlying this effect. Two sets of experiments were performed. In the first set male albino rats (170-210 g) were randomly allocated into a normal control group, ulcer control group (received a single dose of indomethacin 30 mg/kg po) and three ulcer groups pretreated with ranitidine (50 mg/kg po), which was used as a standard anti-ulcer agent, and L-carnitine in two dose levels (100, and 300 mg/kg po) respectively 1 h before ulcer induction. In the second set, male rats were randomly assigned into a normal control and ulcer control groups as in the first set, a third group received NG-nitro-L-arginine-methyl ester (L-NAME) 50 mg/kg ip 1/2 h before indomethacin administration. A fourth and a fifth group received L-carnitine (300 mg/kg po) 1 hour before ulcer induction with indomethacin. The fifth group received in addition L-NAME (50 mg/kg ip) 1/2 h before L-carnitine. The animals were killed 4 h after indomethacin administration and the mucosal tissue was used for gastric injury evaluation both macroscopically and bio-chemically. Indomethacin produced severe ulceration together with disturbed redox state manifested by elevated malondi-aldehyde (MDA) level and lowered reduced glutathione (GSH) content. There is also an increase in myeloperoxidase (MPO) activity, an index of neutrophil infiltration, together with decreased gastric mucosal nitric oxide (NO) content measured as nitrite. Both ranitidine and L-carnitine, signifi-cantly ameliorated the indomethacin-induced gastric lesions as manifested by a significant reduction in ulcer index, with the effect of L-carnitine being dose dependent. This gastro-protective effect was associated with a significant decrease in MDA, increase in GSH, reduction in MPO activity and restoration of gastric mucosal nitrite level to normal control values. Administration of L-NAME significantly exacerbated gastric lesions and reduced the gastroprotective effect of L-carnitine as well as the gastric mucosal nitrite concentration, without altering the effect of L-carnitine on MDA or GSH. These results suggest that L-carnitine has a dose-dependent gastroprotective effect against indomethacin induced ulcer which is comparable to the H2 antagonist ranitidine. This gastroprotective effect is probably due to several mechanisms that include antioxidant activity, inhibition of leukocyte infiltration in the gastric lesion, increasing the availability of NO in the gastric mucosa through reduction of reactive oxygen species (ROS) and increasing the enzymatic produc-
tion of NO from cNOS, probably due to a decreased oxidative uncoupling of the enzyme.