EXPERIMENTAL RESEARCH
The role of L-carnitine in acetyl salicylic acid-induced acute gastric mucosal injury in rats
 
More details
Hide details
 
Submission date: 2016-12-16
 
 
Final revision date: 2017-02-06
 
 
Acceptance date: 2017-02-07
 
 
Publication date: 2017-03-06
 
 
Arch Med Sci Civil Dis 2017;2(1):1-10
 
KEYWORDS
TOPICS
Other
 
ABSTRACT
Introduction: The aim of this study was to determine the protective effects of L-carnitine on acetyl salicylic acid (ASA)-induced acute gastric mucosal injury through oxidant/antioxidant parameters and histopathological alterations in rat gastric tissues.
Material and methods: Forty-two rats were randomly assigned to six groups: The control group received 1 mg/kg distilled water, while the other groups were pretreated with L-carnitine 50 mg/kg/day (LC), pantoprazole 40 mg/kg/day (PPI), ASA + LC (50 mg/kg/day), and ASA + PPI (40 mg/kg/day), for 21 days, respectively. On day 23, gastric mucosal injury was induced by a single intragastric administration of 600 mg/kg aspirin in ASA, ASA + LC, and ASA + PPI groups. The animals were killed 60 min after the administration of aspirin. The stomach of each animal was removed. Gastric mucosal injury was scored histopathologically (ulcer score). Tissue catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities, and malondialdehyde (MDA) and nitric oxide (NO) levels were also measured.
Results: The ulcer score increased significantly in the ASA group, but this increase was not significantly inhibited by the administration of L-carnitine (2.71 ±1.0 vs. 2.57 ±0.5, p = 0.965). The CAT and GSH-Px activities were significantly reduced, whereas MDA and NO levels were significantly increased in the ASA group. Pretreatment with L-carnitine did not alter CAT or GSH-Px activities, but reduced MDA and NO levels insignificantly (p = 0.204 and p = 0.277, respectively).
Conclusions: Long-term administration of L-carnitine did not improve the oxidative and histological parameters of acute gastric mucosal injury induced by ASA.
REFERENCES (73)
1.
Sostres C, Gargallo CJ, Arroyo MT, Lanas A. Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Pract Res Clin Gastroenterol 2010; 24: 121-32.
 
2.
Pohle T, Brzozowski T, Becker JC, et al. Role of reactive oxygen metabolites in aspirin-induced gastric damage in humans: gastroprotection by vitamin C. Aliment Pharmacol Ther 2001; 15: 677-87.
 
3.
Hiraishi H, Shimada T, Ivey KJ, Terano A. Role of antioxidant defenses against ethanol-induced damage in cultured rat gastric epithelial cells. J Pharmacol Exp Ther 1999; 289: 103-9.
 
4.
Zimmerman BJ, Grisham MB, Granger DN. Role of oxidants in ischemia/reperfusion-induced granulocyte infiltration. Am J Physiol Gastrointest Liver Physiol 1990; 258: 185-90.
 
5.
Matthews GM, Butler RN. Cellular mucosal defense during Helicobacter pylori infection: a review of the role of glutathione and the oxidative pentose pathway. Helicobacter 2005; 10: 298-306.
 
6.
Das D, Bandyopadhyay D, Bhattacharjee M, Banerjee RK. Hydroxyl radical is the major causative factor in stress-induced gastric ulceration. Free Radic Biol Med 1997; 23: 8-18.
 
7.
Grisham MB, Granger DN. Neutrophil-mediated mucosal injury: role of reactive oxygen metabolites. Dig Dis Sci 1988; 33: 6-15.
 
8.
Ligumsky M, Klar A, Siguencia J, Arnon R, Gati I, Kohen R. Changes in reducing power profile of gastric juice in patients with active duodenal ulcer. Biomed Pharmacother 2005; 59: 345-50.
 
9.
Rebouche CJ, Paulson DJ. Carnitine metabolism and function in humans. Annu Rev Nutr 1986; 6: 41-66.
 
10.
Roe CR, Millington DS, Maltby DA, Bohan TP, Hoppel CL. L-Carnitine enhances excretion of propionyl coenzyme A as propionylcarnitine in propionic academia. J Clin Invest 1984; 73: 1785-8.
 
11.
Gulewitsch W, Krimberg R. Zur Kenntnis der Extraktivstoffe der Muskeln. II. Mitteilung. Uber das Carnitin. Hoppe-Seyler’s Z Physiol Chem 1905; 45: 326-30.
 
12.
Tomita M, Sendju Y. Uber die Oxyaminoverbindungen, welche die Biuretreaktion ziegen. III. Spaltung der m-amino-b-oxybuttersaure in die optisch-aktiven Komponenten. Hoppe-Seyler’s Z Physiol Chem 1927; 169: 263-77.
 
13.
Rebouche CJ, Seim H. Carnitine metabolism and its regulation in microorganisms and mammals. Ann Rev Nutr 1998; 18: 39-61.
 
14.
Savica V, Calvani M, Benatti P, et al. Carnitine system in uremic patients: molecular and clinical aspects. Semin Nephrol 2004; 24: 464-8.
 
15.
Evans A. Dialysis-related carnitine disorder and levocarnitine pharmacology. Am J Kidney Dis 2003; 41: 13-26.
 
16.
Famularo G, Matricardi F, Nucera E, Santini G, De Simone C. Carnitine deficiency: primary and secondary syndromes. In: Carnitine Today. De Simone C, Famularo G (eds). Landes Bioscience, Austin, TX 1997; 119-61.
 
17.
Pepine CJ. The therapeutic potential of carnitine in cardiovascular disorders. Clin Ther 1991; 13: 2-21.
 
18.
Goa KL, Brogden RN. L-Carnitine. A preliminary review of its pharmacokinetics, and its therapeutic use in ischaemic cardiac disease and primary and secondary carnitine deficiencies in relationship to its role in fatty acid metabolism. Drugs 1987; 34: 1-24.
 
19.
Ahmad S. L-Carnitine in dialysis patients. Semin Dial 2001; 14: 209-17.
 
20.
Arockia Rani PJ, Panneerselvam C. Carnitine as a free radical scavenger in aging. Exp Gerontol 2001; 36: 1713-26.
 
21.
Izgut-Uysal VN, Agac A, Derin N. Effect of carnitine on stress-induced lipid peroxidation in rat gastric mucosa. J Gastroenterol 2001; 36: 231-6.
 
22.
Luo X, Reichetzer B, Trines J, Benson LN, Lehotay DC. L-carnitine attenuates doxorubicin-induced lipid peroxidation in rats. Free Radic Biol Med 1999; 26: 1158-65.
 
23.
Packer L, Valenza M, Serbinova E, Starke-Reed P, Frost K, Kagan V. Free radical scavenging is involved in the protective effect of L-propionyl-carnitine against ischemia-reperfusion injury of the heart. Arch Biochem Biophys 1991; 288: 533-7.
 
24.
Sener G, Paskaloglu K, Satiroglu H, Alican I, Kaçmaz A, Sakarcan A. L-carnitine ameliorates oxidative damage due to chronic renal failure in rats. J Cardiovasc Pharmacol 2004; 43: 698-705.
 
25.
Dokmeci D, Akpolat M, Aydogdu N, Doganay L, Turan FN. L-carnitine inhibits ethanol-induced gastric mucosal injury in rats. Pharmacol Rep 2005; 57: 481-8.
 
26.
Erkin B, Dokmeci D, Altaner S, Turan FN. Gastroprotective effect of L-carnitine on indomethacin-induced gastric mucosal injury in rats: a preliminary study. Folia Med (Plovdiv) 2006; 48: 86-9.
 
27.
Melchiorri D, Sewerynek E, Reiter RJ, Ortiz GG, Poeggeler B, Nisticò G. Suppressive effect of melatonin administration on ethanol-induced gastroduodenal injury in rats in vivo. Br J Pharmacol 1997; 121: 264-70.
 
28.
Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988; 34: 497-500.
 
29.
Aebi H. Catalase. In: Methods of Enzymatic Analysis. Bergmeyer HU (ed.). Academic Press, New York and London 1974; 673-7.
 
30.
Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967; 70: 158-69.
 
31.
Draper HH, Hadley M. Malondialdehyde determination as index of lipid peroxidation. Meth Enzymol 1990; 186: 421-31.
 
32.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265-75.
 
33.
Cortas NK, Wakid NW. Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. Clin Chem 1990; 36: 1440-3.
 
34.
Alvarez A, Pomar F, Sevilla, Montero MJ. Gastric antisecretory and antiulcer activities of an ethanolic extract of Bidens pilosa L. var. radiata Schult. Bip J Ethnopharmacol 1999; 67: 333-40.
 
35.
Scheiman JM. NSAIDs, eicosonoids, and the gastroenteric tract. Gastroenterol Clin North Am 1996; 25: 279-98.
 
36.
Bandyopadhyay U, Das D, Bandyopadhyay D, Bhattacharjee M, Banerjee RK. Role of reactive oxygen species in mercaptomethylimidazole-induced gastric acid secretion and stress-induced gastric ulceration. Curr Sci 1999; 76: 55-63.
 
37.
Pajdo R, Brzozowski T, Szlachcic A, et al. Lipoxins, the novel mediators of gastroprotection and gastric adaptation to ulcerogenic action of aspirin. Curr Pharm Des 2011; 17: 1541-51.
 
38.
Dong MH, Kaunitz JD. Gastroduodenal mucosal defence. Curr Opin Gastroenterol 2006; 22: 599-606.
 
39.
Jainu M, Devi CS. Effect of ambrex (an amber based formulation) on gastric mucosal damage: role of antioxidant enzymes and lipid profile. Indian J Physiol Pharmacol 2004; 48: 343-7.
 
40.
Dharmani P, Mishra PK, Maurya R, Singh Chauhan V, Palit G. Allophylus serratus: a plant with potential anti-ulcerogenic activity. J Ethnopharmacol 2005; 99: 361-6.
 
41.
Umamaheswari M, Asokkumar K, Rathidevi R, Sivashanmugam AT, Subhadradevi V, Ravi TK. Antiulcer and in vitro antioxidant activities of Jasminum grandiflorum L. J Ethnopharmacol 2007; 110: 464-70.
 
42.
Ronca G, Ronca F, Yu G, Zucchi R, Bertelli A. Protection of isolated perfused working rat heart from oxidative stress by exogenous L-propionyl carnitine. Drugs Exp Clin Res 1992; 18: 475-80.
 
43.
Di Giacomo C, Latteri F, Fichera C, et al. Effect of acetyl-L-carnitine on lipid peroxidation and xanthine oxidase activity in rat skeletal muscle. Neurochem Res 1993; 18: 1157-62.
 
44.
Arafa HM, Sayed-Ahmed MM. Protective role of carnitine esters against alcohol-induced gastric lesions in rats. Pharmacol Res 2003; 48: 285-90.
 
45.
Valoti M, Benocci A, Marazova K, Mantovani P. Effects of carnitine and its derivatives on gastric acid secretion in rats. Pharmacol Res 1996; 34: 219-24.
 
46.
Izgut-Uysal VN, Bülbül M, Tan R, et al. Effect of chronic stress and L-carnitine on rat stomach. J Physiol Sci 2007; 57: 187-92.
 
47.
Bandyopadhyay D, Biswas K, Bhattacharyya M, Reiter RJ, Banerjee RK. Involvement of reactive oxygen species in gastric ulceration: protection by melatonin. Indian J Exp Biol 2002; 40: 693-705.
 
48.
Khosla P, Karan RS, Bhargava VK. Effect of garlic oil on ethanol induced gastric ulcers in rats. Phytother Res 2004; 18: 87-91.
 
49.
Naito Y, Yoshikawa T, Matsuyama K, et al. Effects of oxygen radical scavengers on the quality of gastric ulcer healing in rats. J Clin Gastroenterol 1995; 21: 82-6.
 
50.
Oates PJ, Hakkinen JP. Studies on the mechanism of ethanol-induced gastric damage in the rat. Gastroenterology 1988; 94: 10-21.
 
51.
Robert A, Lancaster C, Davis JP, Field SO, Sinha AJ, Thornburgh BA. Cytoprotection by prostaglandin occurs in spite of penetration of absolute ethanol into the gastric mucosa. Gastroenterology 1985; 88: 328-33.
 
52.
Mizui T, Doteuchi M. Lipid peroxidation. A possible role in gastric damage induced by ethanol in rats. Life Sci 1986; 38: 2163-7.
 
53.
Akgun S, Tekeli A, Kurtkaya O, et al. Neuroprotective effects of FK-506, L-carnitine and azathioprine on spinal cord ischemia-reperfusion injury. Eur J Cardiothorac Surg 2004; 25: 105-10.
 
54.
Kocer I, Kulacoglu D, Altuntas I, Gundogdu C, Gullulu G. Protection of the retina from ischemia-reperfusion injury by L-carnitine in guinea pigs. Eur J Ophthalmol 2003; 13: 80-5.
 
55.
Loster H, Bohm U. L-carnitine reduces malondialdehyde concentrations in isolated rat hearts in dependence on perfusion conditions. Mol Cell Biochem 2001; 217: 83-90.
 
56.
Kawasaki N, Lee JD, Shimizu H, Ueda T. Long-term L-carnitine treatment prolongs the survival in rats with adriamycin-induced heart failure. J Card Fail 1996; 2: 293-9.
 
57.
Sayed-Ahmed MM, Salman TM, Gaballah HE, Abou El-Naga SA, Nicolai R, Calvani M. Propionyl-L-carnitine as protector against adriamycin-induced cardiomyopathy. Pharmacol Res 2001; 43: 513-20.
 
58.
Sayed-Ahmed MM, Shaarawy S, Shouman SA, Osman AM. Reversal of doxorubicin-induced cardiac metabolic damage by L-carnitine. Pharmacol Res 1999; 39: 289-95.
 
59.
Pauly DF, Pepine CJ. The role of carnitine in myocardial dysfunction. Am J Kidney Dis 2003; 41: 35-43.
 
60.
Singh RB, Niaz MA, Agarwal P, Beegum R, Rastogi SS, Sachan DS. A randomized, double-blind, placebo controlled trial of L-carnitine in suspected acute myocardial infarction. Postgrad Med J 1996; 72: 45-50.
 
61.
Auguste L, Sterman HR, Stein TA, Bailey B, Wise L. Effect of verapamil on the gastric mucosal level of PGE2 during stress. J Surg Res 1990; 49: 34-6.
 
62.
Victor BE, Schmidt KL, Smith GS, Reed RL, Thompson DA, Miller TA. Prostaglandin-induced gastric mucosal protection against stress injury. Absence of a relationship to tissue glutathione levels. Ann Surg 1989; 209: 289-96.
 
63.
Takezono Y, Joh T, Oshima T, et al. Role of prostaglandins in maintaining gastric mucus-cell permeability against acid exposure. J Lab Clin Med 2004; 143: 52-8.
 
64.
Garrelds IM, Elliott GR, Zijlstra FJ, Bonta IL. Effects of short and long term feeding of l-carnitine and congeners on the production of eicosanoids from rat peritoneal leucocytes. Br J Nutr 1994; 72: 785-93.
 
65.
Derin N, Agac A, Bayram Z, Asar M, Izgut-Uysal VN. Effects of L-carnitine on neutrophil-mediated ischemia-reperfusion injury in rat stomach. Cell Biochem Funct 2006; 24: 437-42.
 
66.
Naito Y, Yoshikawa T, Yoshida N, Kondo M. Role of oxygen radical and lipid peroxidation in indomethacin-induced gastric mucosal injury. Dig Dis Sci 1998; 43: 30-4.
 
67.
Sonne S, Shekhawat PS, Matern D, Ganapathy V, Ignatowicz L. Carnitine deficiency in OCTN2-/- newborn mice leads to a severe gut and immune phenotype with widespread atrophy, apoptosis and a pro-inflammatory response. PLoS One 2012; 7: e47729.
 
68.
De Preter V, Geboes KP, Bulteel V, et al. Kinetics of butyrate metabolism in the normal colon and in ulcerative colitis: the effects of substrate concentration and carnitine on the beta-oxidation pathway. Aliment Pharmacol Ther 2011; 34: 526-32.
 
69.
Scioli MG, Stasi MA, Passeri D, et al. Propionyl-L-carnitine is efficacious in ulcerative colitis through its action on the immune function and microvasculature. Clin Transl Gastroenterol 2014; 5: e55.
 
70.
Akpolat M, Gulle K, Topcu-Tarladacalisir Y, et al. Protection by L-carnitine against radiation-induced ileal mucosal injury in the rat: pattern of oxidative stress, apoptosis and cytokines. Int J Radiat Biol 2013; 89: 732-40.
 
71.
Tas S, Ozkan OF, Cikman O, Kiraz A, Akgun Y, Karaayvaz M. L-carnitine has a protective effect on the colonic mucosa during abdominopelvic radiotherapy in rats. Acta Cir Bras 2016; 31: 615-20.
 
72.
Matsuda K, Yuasa H, Watanabe J. Physiological mechanism-based analysis of dose-dependent gastrointestinal absorption of L-carnitine in rats. Biopharm Drug Dispos 1998; 19: 465-72.
 
73.
Matsuda K, Yuasa H, Watanabe J. Fractional absorption of L-carnitine after oral administration in rats: evaluation of absorption site and dose dependency. Biol Pharm Bull 1998; 21: 752-5.
 
ISSN:2451-0637
Journals System - logo
Scroll to top