Protective effect of L-carnitine against ethanol-induced gastric damage: investigation of possible mechanisms of action

Abstract

The underlying mechanisms of L-carnitine’s (L-CAR) protective effect against ethanol (EtOH)-induced gastric mucosal damage were investigated in this study. The rats were randomly divided into four groups: control (CON), EtOH, EtOH + L-CAR50, and EtOH + LCAR100. Control group was given saline (5 mL/kg) twice at 1-hour interval. EtOH group was given 5 mL/kg saline 1-hour before absolute EtOH administration (5 mL/kg). EtOH + LCAR50 group received 50 mg/kg LCAR 1-hour before absolute EtOH administration (5 mL/kg). EtOH + LCAR100 group received 100 mg/kg LCAR 1-hour before absolute EtOH administration (5 mL/kg). All the rats were euthanized 1 hour after the administration of EtOH. The gastric lesion area was grossly examined, and gastric lesions were histopathologically evaluated. Real-time PCR was used to examine the expression of cyclooxygenase 1 and 2 (COX-1 and COX-2), inducible- and endothelial- nitric oxide synthase (iNOS and eNOS), tumor necrosis factor alpha (TNF-α), heat shock protein 70 (HSP70), and trefoil factor 2 (TFF2) mRNA in the gastric mucosa. Histopathological examination revealed that L-CAR treatment reduced the severity and extent of gastric lesions caused by EtOH administration, such as shedding of the superficial epithelium, glandular gland necrosis, intralesional hemorrhage, submucosal edema, and neutrophil infiltration. L-CAR administration was found to significantly reduce the mRNA levels of COX-2, iNOS, eNOS, and TNF-α in the gastric mucosa compared to EtOH administration alone. It was determined that L-CAR administration further increased the gastric mucosal HSP70 mRNA expression than EtOH administration alone. L-CAR treatment increased TFF2 expression which was decreased after EtOH administration. Finally, L-CAR administration was thought to protect against EtOH-induced gastric mucosal damage by regulating the expression of gastric mucosal COX and NOS systems, reducing the inflammatory cytokine levels, inducing a cellular stress response, and stimulating the expression of factors associated with mucus secretion and gastric epithelium restitution.

Keywords

• cyclooxygenase
• ethanol
• heat shock protein
• L-carnitine
• nitric oxide synthetase
• trefoil peptides

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