|Year : 2008 | Volume
| Issue : 5 | Page : 209-214
Antiulcer activity of cod liver oil in rats
Salaj Khare1, Mohammed Asad1, Sunil S Dhamanigi1, V Satya Prasad2
1 Krupanidhi College of Pharmacy, Bangalore, India
2 MNR Medical College, Andhra Pradesh, India
|Date of Submission||31-Mar-2008|
|Date of Decision||26-Jul-2008|
|Date of Acceptance||14-Oct-2008|
Krupanidhi College of Pharmacy, Bangalore
Objective: Cod liver oil is used widely as a dietary supplement. The present study was carried out to evaluate the effect of cod liver oil (0.5 g/kg, p.o. and 1 g/kg, p.o.) on gastric and duodenal ulcers.
Materials and Methods: The study was carried out on different gastric ulcer models such as acetic acid induced chronic gastric ulcers, pylorus ligation, indomethacin induced ulcers, stress induced ulcers and ethanol induced ulcers. The duodenal ulcers were induced using cysteamine hydrochloride (HCl). Ranitidine (50 mg/kg p.o.) and misoprostol (100 µg/kg, p.o.) were used as standard drugs.
Results: Both doses of cod liver oil showed gastric ulcer healing effect in acetic acid induced chronic gastric ulcers, produced gastric antisecretory effect in pylorus-ligated rats and also showed gastric cytoprotective effect in ethanol-induced and indomethacin-induced ulcer. Cod liver oil also produced a significant reduction in the development of stress induced gastric ulcers and cysteamine induced duodenal ulcer. The high dose of cod liver oil (1 g/kg, p.o.) was more effective compared to the low dose (0.5 g/kg, p.o.).
Conclusion: Cod liver oil increases healing of gastric ulcers and prevents the development of experimentally induced gastric and duodenal ulcers in rats.
Keywords: Cod liver oil, duodenal ulcer, gastric cytoprotection, gastric secretion, gastric ulcer
|How to cite this article:|
Khare S, Asad M, Dhamanigi SS, Prasad V S. Antiulcer activity of cod liver oil in rats. Indian J Pharmacol 2008;40:209-14
| » Introduction|| |
Cod liver oil (CLO) is a dietary supplement that consists of polyunsaturated fatty acids (PUFA), which includes C 20 fatty acids (17%), palmitoleic acid (7%) and C 22 fatty acids (11%), vitamin A not less than 850 USP units/g and vitamin D not less than 85 USP units/g. , Cod liver oil is widely used in the treatment of rickets and osteomalacia as a dietary supplement.
The development and progression of gastric ulcer, to some extent, depends on the type of the food consumed by the patient. Studies have been carried out to specifically evaluate the effect of fish oils on the development of gastric ulcer. It has been reported that a diet rich in fish oils reduces arachidonic acid levels in the gastric mucosa and increases stress induced gastric erosions.  On the contrary, it is reported that fish oils rich in polyunsaturated fatty acids (PUFA) reduce the development of dexamethasone induced gastric damage.  Similarly, vitamin E present abundantly in fish oils is reported to reduce the development of indomethacin induced gastric damage. 
Cod liver oil is obtained from the liver of the cod fish and is different from fish oil. The main difference is that CLO is rich in vitamin A and vitamin D, as compared to fish oil and both these vitamins have therapeutic effects. , Earlier studies carried out with CLO indicate that CLO inhibits the development of indomethacin induced gastric ulcers in rats.  However, other studies suggest that CLO may inhibit the formation of arachidonic acid and may thus decrease the production of cytoprotective prostaglandins leading to the development of gastric ulcers, especially under conditions of stress.  The exact effect of CLO administration on the healing or development of gastric ulcer is not known. Since CLO is widely used as a dietary supplement, the present study was undertaken to evaluate its effect on the development and healing of gastric and duodenal ulcers in rats.
| » Materials and Methods|| |
Male albino Wistar rats weighing between 200 and 250 gm were used. The experimental protocol was approved by the Institutional Animal Ethics Committee. The animals were maintained under standard conditions in an animal house approved by the Committee for the Purpose of Control and Supervision on Experiments on Animals (CPCSEA).
Drugs and chemicals
Acetic acid (E-Merck, Mumbai, India), cysteamine hydrochloride (Hi-media, Mumbai, India), ethanol (Bengal Chemicals, Kolkatta, India), indomethacin (Sigma, St. Louis, MO, USA), ketamine hydrochloride (Troika Parentrals, Gujarat, India) and CLO (Universal Medicare Pvt. Ltd., Mumbai, India).
Determination of purity of CLO
The monographic analysis of CLO was carried out using procedures mentioned in the British Pharmacopoeia,  the United States Pharmacopoeia  and the Indian Pharmacopoeia.
| » Gastric Ulcers|| |
Acetic acid-induced chronic gastric ulcer
The method described by Okabe et al. (1970)  was followed. The animals were fasted for 24 h prior to the experiment. Under light ether anaesthesia, ulcers were induced by applying glacial acetic acid (0.05 ml) over the anterior serosal surface of the stomach for 60 seconds. The animals were treated with ranitidine (50 mg/kg, p.o.),  low dose of CLO (0.5 g/kg p.o.)  or high dose of CLO (1 g/kg p.o.),  once daily, for 10 days after the induction of ulcer, while the control group received only the vehicle. The rats were sacrificed on the 10 th day, the stomachs removed and cut open along the greater curvature.
The ulcer index was determined using the formula: 
Ulcer index = 10/X
Where X = Total mucosal area/Total ulcerated area.
Based on their intensity, the ulcers were given scores as follows:
0 = no ulcer, 1 = superficial mucosal erosion, 2 = deep ulcer or transmural necrosis, 3 = perforated or penetrated ulcer.
Pylorus ligation induced ulcers
The ligation of pyloric end of the stomach was performed on animals fasted for 36 h, under ether anaesthesia. , The two doses of CLO or ranitidine was administered intraduodenally, immediately after pylorus ligation. The animals were sacrificed six hours after pylorus ligation, through an overdose of ether anaesthesia. The stomachs were isolated and the content collected and centrifuged. The volume of the gastric juice was measured and this was used for the estimation of free acidity,  total acidity  pepsin content  and total proteins.  The ulcer index and gastric mucous content was determined. 
Healing of indomethacin induced gastric ulcers
The gastric ulcers were induced by administering indomethacin (5 mg/kg. p.o.) for five days.  The animals were then treated either with misoprostol (100 µg/kg, p.o),  low dose of CLO (0.5 g/kg p.o.) or high dose of CLO (1 g/kg p.o.), once daily for another five days, after the induction of ulcer, while the control group received only vehicle. The rats were sacrificed on the fifth day and the ulcer index was determined. The glandular portion of the stomach was taken and used for estimation of mucin content,  total proteins,  antioxidant factor's super oxide dismutase activity  and catalase activity.
Ethanol induced ulcers
All the animals were fasted for 36 h before the administration of ethanol. The standard drug (misoprostol 100 µg/kg, p.o.) or CLO was administered one hour before ethanol administration. Ethanol (90%) was administered to all the animals at a dose of 1 ml/200gm and after one hour, all the animals were sacrificed and ulcer index was determined as mentioned above. 
Cold restraint stress induced ulcers
The ulcer was induced by subjecting the animals to cold restraint stress. Ranitidine or CLO was administered 30 min prior to subjecting the animals to stress. The animals were placed in a restraint cage and the cage was placed at a temperature of 2°C for 3 h. The animals were sacrificed after three hours and the ulcer index was determined. ,
| » Duodenal Ulcers|| |
Cysteamine induced duodenal ulcers
Duodenal ulcer was induced by administering cysteamine hydrochloride (400 mg/kg, p.o.) twice, at an interval of four hours. Ranitidine or CLO was administered 30 min prior to each dose of cysteamine hydrochloride. After 24 h, all the animals were sacrificed and the duodena were excised carefully and cut open along the antimesentric side. The duodenal ulcer area, ulcer score and ulcer index were determined. 
Based on their intensity, the ulcers were given scores as follows:
0 = no ulcer, 1 = superficial mucosal erosion, 2 = deep ulcer or transmural necrosis,
3 = perforated or penetrated ulcer.
The ulcer index was calculated using the following equation: 
The statistical significance was assessed using one-way analysis of variance (anova) followed by Bonferrroni's comparison test. For comparing nonparametric ulcer scores, anova followed by non-parametric Dunn post test was used. The values are expressed as mean ± SEM and P <0.05 was considered significant.
| » Results|| |
Determination of purity of CLO
The monographic analysis of CLO revealed the following results:
Saponification value - 185.13
Acid value - 1.12
Refractive index - 1.475
The assay of vitamin A was carried out as per the United States Pharmacopoeia and the vitamin A content was 2133 IU /ml.
The assay of vitamin D was carried out using the HPLC method mentioned in the Indian Pharmacopoeia and the CLO sample was found to contain 114 IU/ml of vitamin D.
All the values are within the limits prescribed by the pharmacopoeia.
Acetic acid-induced chronic gastric ulcer
The CLO produced a significant reduction in the ulcer index and the ulcer score. Both the high dose (1 g/kg, p.o.) and the low dose of CLO (0.5 g/kg, p.o.) were effective in reducing the ulcer index and the ulcer score, when compared to control. The high dose of CLO was significantly more effective than the low dose in reducing the ulcer index. Ranitidine was most effective in reducing both ulcer score and ulcer index [Table 1].
Pylorus ligation induced gastric ulcers
Both doses of CLO produced a significant reduction in the ulcer index, free acidity, total acidity and pepsin content, when compared to control. The effects observed were dose dependent, with high dose of CLO (1 g/kg, p.o.) showing more effect, as compared to the low dose (0.5 g/kg, p.o.). The mucin content and total protein were significantly increased by both doses of CLO in a dose dependent manner, when compared to control. Ranitidine also showed similar effects, but was more effective compared to both doses of CLO [Table 2].
Healing of indomethacin induced gastric ulcers
The healing of indomethacin induced gastric ulcers was significantly increased by both doses of CLO, as indicated by a reduction in the ulcer index. Both the doses of CLO also produced a significant increase in mucin content, superoxide dismutase and catalase activity, with the high dose showing more activity, as compared to the low dose. The standard drug misoprostol reduced the ulcer index and increased gastric mucus secretion, but did not affect the protein content or enzyme activity [Table 3].
Ethanol induced and cold restraint stress induced ulcers
Both the doses of CLO showed a significant reduction in the ulcer index, when compared to control. Misoprostol and ranitidine showed more reduction in the ulcer index than CLO, in ethanol induced and cold restraint stress induced ulcer models respectively [Table 4] and [Table 5]
Cysteamine induced duodenal ulcers
Both the doses of CLO produced significant reduction in the ulcer index, the ulcer area and the ulcer score, when compared to control. The high dose ( P <0.001) of CLO showed more significant effect in ulcer area and ulcer score than the low dose. Ranitidine completely prevented the development of duodenal ulcers. The ulcer was developed in the anti-mesenteric side of the duodenum [Table 6].
| » Discussion|| |
The present study investigated the effect of CLO on the gastric and duodenal ulcers. Cod liver oil showed effect on the healing of gastric ulcers induced by acetic acid and prevented the development of gastric ulcers induced by different methods and cysteamine induced duodenal ulcer.
Application of glacial acetic acid (0.05ml) on the serosal surface of the stomach produced deep penetrating gastric ulcer that resembles human peptic ulcer disease. Since the healing process of this ulcer closely resembles that of human peptic ulcers, this model is quite useful for studying the effect of drugs on the healing of peptic ulcers.  CLO was effective in augmenting the gastric ulcer healing in this model. To evaluate the mechanism by which CLO increased gastric ulcer healing, further studies were carried out using other models of gastric ulcers.
Pylorus ligation induced ulcer is one of the most widely used methods for studying the effect of drugs on gastric secretion. Agents that decrease gastric acid secretion and/or increase mucus secretion are effective in preventing the ulcers induced by this method. The ligation of the pyloric end of the stomach causes accumulation of gastric acid in the stomach, leading to the development of ulcers in the stomach. The original Shay rat model involves fasting of rats for 72 h, followed by ligation of the pyloric end of the stomach for 19 h.  In the present study, the modification of Shay rat model described by Kulkarni  was followed, which involves fasting of the animals for 36 h and pyloric ligation only for six hours. Ranitidine and CLO significantly decreased the secretion of gastric aggressive factors, free acidity, total acidity and pepsin content, and increased the mucus secretion, which is cytoprotective.
Ethanol induced gastric ulcer and indomethacin induced gastric ulcers were employed to study the cytoprotective effect of CLO. Ethanol induces gastric lesion, due to its corrosive effect. It rapidly penetrates the gastric mucosa, causing cell and plasma membrane damage, leading to increased membrane permeability to sodium and water. It also produces massive intracellular accumulation of calcium, which represents a major step in the pathogenesis of gastric mucosal injury. This leads to cell death and exfoliation in the surface epithelium. , Both the doses of CLO were effective in preventing development of ethanol induced gastric ulcers, indicating that CLO possesses gastric cytoprotective effect.
Indomethacin produces erosions and ulcers in the stomach due to the inhibition of prostaglandin synthesis.  The gastric cytoprotective agents are effective in preventing ulcers induced by indomethacin. Like ethanol induced gastric ulcers, CLO was effective in reducing ulcer index and in increasing the mucus content. Further, CLO produced an increased activity of antioxidant enzymes, suggesting that its effect on ulcer may partly be due to its antioxidant action.
The pathophysiology of stress-induced ulcers is complex; the ulcers are produced due to the release of histamine, leading to an increase in acid secretion and a reduction in mucus production. [35, Stress also causes an increase in gastrointestinal motility, which causes folds in the gastrointestinal tract The folds in the stomach are more susceptible to damage, when they come in contact with acid. The stress also brings the central nervous system into play. Agents that decrease G.I. motility, gastric secretion or those having central actions are helpful in reducing ulcers due to stress. Ranitidine and CLO were effective in reducing ulcers induced by stress. The reduction in stress induced gastric ulcers may probably be due to the reduction in gastric secretion, as there are no reports to indicate the effect of CLO on gastric motility or the central nervous system.
Cysteamine induced duodenal ulcer in rat resembles that of duodenal ulcer in humans, histopathologically and pathophysiologically. Cysteamine hydrochloride inhibits the alkaline mucus secretion from the Brunner's glands in the proximal duodenum and stimulates the rate of gastric acid secretion. Gastric emptying is also delayed and serum gastrin concentration is increased. 
Cod liver oil was effective in reducing the ulcer area and the ulcer score. The effect of fish oil on the development of gastric and duodenal ulcers has been studied extensively. Fish oil is reported to reduce gastric secretion and also prevent the development of indomethacin induced gastric ulcers. , Fish oil is also used as dietary supplements for ulcerative colitis.
As mentioned earlier, CLO inhibits the development of indomethacin induced gastric ulcers in rats.  However, other studies suggest that CLO may inhibit the formation of arachidonic acid and may thus decrease the production of cytoprotective prostaglandnins, leading to the development of gastric ulcers, especially under conditions of stress. 
Although earlier reports on the effect of CLO on gastric ulcers are confusing, studies carried out using different constituents of fish oils such as omega-3-fatty acid and polyunsaturated fatty acids reveal that they possess antiulcer and antioxidant effect. Omega 3 triglycerides are also known to inhibit ulcer formation in pylorus ligated rats  and increase healing of gastric ulcers in rats.  Omega-3-fatty acid also possesses antioxidant effect.  Fish oil, rich in omega-3-fatty acid, is reported to inhibit offensive mucosal factors and oxidative stress and to augment defensive mucosal factors.  Further, fish oil reduced development of cold plus restraint ulcers in rats. 
Polyunsaturated fatty acids (PUFA) are reported to reduce the development of dexamethasone induced and indomethacin induced gastric ulcers healing. , Moreover, decrease in intake of polyunsaturated fatty acid was shown to be associated with increased incidence of duodenal ulcers in humans. 
The exact constituents and the mechanism by which CLO reduced gastric and duodenal ulcer formation and increased gastric ulcer cannot be explained by the present data. However, it is speculated that the polyunsaturated fatty acid and the omega-3-fatty acids present abundantly in the CLO may be responsible for this effect. Furthermore, the antioxidant effect of CLO may also be responsible for its anti-ulcer action. 
The results of the present investigation suggest that consumption of CLO is beneficial for patients suffering from peptic ulcer disease. Cod liver oil may produce both gastric antisecretory and gastric cytoprotective effect, resulting in increased healing of gastric and duodenal ulcers. However, the effect of CLO on the growth of Helicobacter pylori , one of the main causes for the development of gastric and duodenal ulcer, is not known. Studies on the effect of CLO on the Helicobacter pylori infection have to be carried out to further support the beneficial effect of CLO in peptic ulcer patients.
| » Conclusion|| |
Cod liver oil has an antiulcer effect. It increased healing of acetic acid induced chronic gastric ulcers and prevented the development of gastric ulcers induced by pylorus ligation, ethanol, stress or indomethacin. Cod liver oil was also effective in preventing the development of cysteamine induced duodenal ulcers.
| » Acknowledgement|| |
The authors are thankful to Prof. Suresh Nagpal, Chairman, Krupanidhi Educational Trust (Bangalore, India), for funding the research work and Dr. Amit Kumar Das, Professor and Principal, Krupanidhi College of Pharmacy for his suggestions.
| » References|| |
|1.||Zamora A. Fatty acid composition of some common edible fats and oils. Available from: http://www.scientificpsychic.com. [last retrieved on 2005 Oct 16]. |
|2.||Wilton P. Cod-liver oil, vitamin D and the fight against rickets. CMAJ 1995;152:1516-7. [PUBMED] [FULLTEXT]|
|3.||Olafsson SO, Hallgrimsson J, Gudbjarnason S. Dietary cod liver oil decreases arachidonic acid in rat gastric mucosa and increases stress-induced gastric erosions. Lipids 2000;35:601-5. [PUBMED] |
|4.||Manjari V, Das UN. Effect of polyunsaturated fatty acids on dexamethasone-induced gastric mucosal damage. Prostagland Leukot Essent Fatty Acids 2000;62:85-96. |
|5.||Zaror-Behrens G, Mueller R, Greselin E, Behrens WA. Lack of vitamin E cytoprotective effects on indomethacin-induced gastric lesions. Res Commun Chem Pathol Pharmacol 1991;72:327-35. [PUBMED] |
|6.||Available from: http://www.mercola.com/forms/faq/carlsons.htm. [last retrieved on 2008 Aug 21]. |
|7.||Available from: http://en.wikipedia.org/wiki/Cod_liver_oil. [last retrieved on 2008 Aug 21]. |
|8.||Bernhard W, Postle AD, Linck M, Sewing KF. Rat gastric hydrophobic barrier: Modulation of phosphatidylcholine molecular species by dietary lipids. Lipids 1996;31:507-11. [PUBMED] |
|9.||British pharmacopoeia 1988;1:123. |
|10.||United States Pharmacopoeia 2006; p-571. |
|11.||Indian Pharmacopoeia 1996;2:A62-3. |
|12.||Okabe S, Pfeiffer CJ, Roth JL. Experimental production of duodenal and antral ulcers in rats. Fed Proc 1970;29:255. |
|13.||Asad M, Shewade DG, Koumaravelou K, Abraham BK, Vasu S, Ramaswamy S. Gastric anti-secretary anti-ulcer activity of oxytocin in rats and guinea pigs. Life Sci 2001;70:17-24. [PUBMED] |
|14.||el Tahir KE, Hamad EA, Ageel AM, Abu Nasif MA, Gadkarim EA. Effects of sesame and cod liver oils on prostacyclin synthesis by the rat thoracic aorta. Arch Int Pharmacodyn Ther 1988;292:182-8. [PUBMED] |
|15.||Ganguly AK. A method for quantitative assement of experimentally produced ulcers in stomach of rats. Experientia 1969;25:1124. |
|16.||Shay H, Komarov SA, Fele SS, Meranze D, Gruenstein H, Siplet H. A simple method for uniform production of gastric ulceration in rat. Gastroenterology 1945;5:43-61. |
|17.||Kulkarni SK. Hand book of experimental pharmacology. 3rd ed. New Delhi: Vallabh Prakashan; 1999. p. 148-50. |
|18.||Hawk PB, Oser BL, Summerson HW. Practical physiological chemistry. 12th ed. London: Churchill; 1947. p. 347. |
|19.||Debnath PK, Gode KO, Govinda DD, Sanyal AK. Effect of propranolol on gastric secretion in rats. Br J Pharmacol 1974;51:213-6. |
|20.||Lowry CH, Roseborough NI, Farr AL, Randall RJ. Protein measurement with folin phenol reagent. J Biol Chem 1951;193:265-75. |
|21.||Corne SJ, Morrissey SM, Woods RJ. A method for the quantitative estimation of gastric barrier mucus. J Physiol 1974;242:116-7. |
|22.||Brzozowski T, Konturek SJ, Kwiecien S, Pajdo R, Brzozowski I, Hahn EG, et al. Involvement of endogenous cholecystokinin and somatostatin in gastro protection induced by intra duodenal fat. J Clin Gastroenterol 1998;27:125-37. |
|23.||Majumdar B, Chaudhri SG, Ray A, Bandyopadhyay SK. Effect of ethanol extract of piper betle linn leaf on healing of NSAID-induced experimental ulcer-A novel role of free radical scavenging action. Indian J Exp Biol 2003;41:311-5. |
|24.||Elstner EF, Heupel A. Inhibition of nitrite formation from hydroxyl ammonium chloride: A simple assay for super oxide dismutase. Anal Biochem 1976;70:616-20. [PUBMED] |
|25.||Eva ML. Mechanism of pH dependent hydrogen per oxide cytotoxicity invitro. Arch Biochem Biophy 1988;365:362-72. |
|26.||Lacy ER, Hund P 3rd, Tietge J. Effects of misoprostol, cimetidine and ethanol on rat gastric plasma volume and morphology. J Clin Gastroenterol 1990;12:S158-69. [PUBMED] |
|27.||Parmar NS, Desai JK. A review of the current methodology for the evaluation of gastric and duodenal anti ulcer agents. Indian J Pharmacol 1993;25:120-35. |
|28.||Vincent GP, Galvin GB, Rutkowski JL, Pare W. Body orientation, food deprivation and potentiation of restraint induced gastric lesions. Gastroenterol Clin Biol 1977;1:539-43. |
|29.||Szabo S. Animal model for human disease: Duodenal ulcer disease. Am J Pathol 1978;73:273-6. |
|30.||Desai JK, Goyal RK, Parmar NS. Characterization of dopamine receptor subtypes involved in experimentally induced gastric and duodenal ulcers in rats. J Pharm Pharmacol 1999;51:187-92. [PUBMED] [FULLTEXT]|
|31.||Okabe S, Roth JL, Pfeiffer CJ. Differential healing periods of the acetic acid ulcer model in rats and cats. Experientia 1971;27:146-8. [PUBMED] |
|32.||Soll AH. Pathogenesis of peptic ulcers and implication for therapy. N Engl J Med 1990;322:909-16. [PUBMED] |
|33.||Surendra S. Evaluation of gastric anti-ulcer activity of fixed oil of tulsi and possible mechanism. Indian J Exp Biol 1999;36:253-7. |
|34.||Vedavyasa S. Gastric mucosal cellular changes induced by indomethacin in male albino rats. Indian J Exp Biol 1999;37:365-9. |
|35.||Peters MN, Richardson CT. Stressful life events, acid hyper secretion and ulcer disease. Gastroenterology 1983;84:114-9. [PUBMED] |
|36.||Brodie DA, Hanson HM. A study of the factors involved in the production of gastric ulcers by the restraint technique. Gastroenterology 1960;38:353-60. [PUBMED] |
|37.||Güzel C, Ulak G, Sermet A, Ciηek R, Ulak M. Effect of fish oil on indometacin-induced gastric lesions in rats. Arzneimittelforschung 1995;45:1172-3. |
|38.||Riber C, Wojdemann M, Bisgaard T, Ingels H, Rehfeld JF, Olsen O. Fish oil reduces gastric acid secretion. Scand J Gastroenterol 1999;34:845-8. |
|39.||Stenson WF, Cort D, Rodgers J, Burakoff R, DeSchryver-Kecskemeti K, Gramlich TL, et al. Dietary supplementation with fish oil in ulcerative colitis. Ann Intern Med 1992;11:609-14. |
|40.||Al-Meshal MA, Lutfi KM, Tariq M. Cod liver oil inhibits indomethacin induced gastropathy without affecting its bioavailability and pharmacological activity. Life Sci 1991;48:1401-9. [PUBMED] |
|41.||Al-Harbi MM, Islam MW, al-Shabanah OA, al-Gharably NM. Effect of acute administration of fish oil (omega-3 marine triglyceride) on gastric ulceration and secretion induced by various ulcerogenic and necrotizing agents in rats. Food Chem Toxicol 1995;33:553-8. [PUBMED] [FULLTEXT]|
|42.||Takada H, Takahashi M, Takada H, Kuwayama H, Souma R. Omega.3 polyunsaturated fatty acid and ulcer healing. Dokkyo J Med Sci 2004;31:17-223. |
|43.||Hasan E, Ersin F, Salih O, Sadik S, Birsen O, Omer A, et al. Effect of fish oil supplementation on plasma oxidant/antioxidant status in rats. Prostagland Leukot Essent Fatty Acids 2004;71:149-52. |
|44.||Bhattacharya A, Ghosal S, Bhattacharya SK. Effect of fish oil on offensive and defensive factors in gastric ulceration in rats. Food Chem Toxicol 1995;33:553-8. |
|45.||Ulak G, Ciηek R, Sermet A, Guzel C, Ulak M, Denli O. Protective effect of fish oil against stress-induced gastric injury in rats. Arzneimittelforschung 1995;45:1174-5. |
|46.||Shimizu T, Suzuki M, Lee T, Igarashi J, Kaneko K, Yamashiro Y. Effects of n-3 polyunsaturated fatty acids on indomethacin-induced changes in eicosanoid production and blood flow in the gastric mucosa of rats. Prostagland Leukot Essent Fatty Acids 2003;69:33-7. |
|47.||Grant HW, Palmer KR, Riermesma RR, Oliver MF. Duodenal ulcer is associated with low dietary linoleic acid intake. Gut 1990;31:997-8. [PUBMED] [FULLTEXT]|
|48.||Hünkar T, Aktan F, Ceylan A, Karasu C; Antioxidants in Diabetes-Induced Complications (ADIC) Study Group. Effects of cod liver oil on tissue antioxidant pathways in normal and streptozotocin-diabetic rats. Cell Biochem Funct 2002;20:297-302. |
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
|This article has been cited by|
||Hepatoprotective effects of cod liver oil against sodium nitrite toxicity in rats
| ||Mohamed F. Salama,Ahmed Abbas,Mohamed M. Darweish,Amany A. El-Hawwary,Mohammed M. H. Al-Gayyar |
| ||Pharmaceutical Biology. 2013; 51(11): 1435 |
||Prostaglandin Analogous and Antioxidant Activity Mediated Gastroprotective Action of Tabernaemontana divaricata (L.) R. Br. Flower Methanolic Extract against Chemically Induced Gastric Ulcers in Rats
| ||Mohammed Safwan Ali Khan,Abdul Manan Mat Jais,Adiba Afreen |
| ||BioMed Research International. 2013; 2013: 1 |
||Methanol Extract ofBauhinia purpureaLeaf Possesses Anti-Ulcer Activity
| ||Z.A. Zakaria,E.E. Abdul Hisam,M. Norhafizah,M.S. Rofiee,F. Othman,A.H. Hasiah,M. Vasudevan |
| ||Medical Principles and Practice. 2012; 21(5): 476 |
||Investigation of gastro protective activity of Xanthium strumarium L. by modulation of cellular and biochemical marker
| ||Amit D. Kandhare,V. Shiva Kumar,Mohammad Adil,Anuchandra R. Rajmane,Pinaki Ghosh,Subhash L. Bodhankar |
| ||Oriental Pharmacy and Experimental Medicine. 2012; 12(4): 287 |
||In vivo antiulcer activity of the aqueous extract of Bauhinia purpurea leaf
| ||Z.A. Zakaria, E.E. Abdul Hisam, M.S. Rofiee, M. Norhafizah, M.N. Somchit, L.K. Teh, M.Z. Salleh |
| ||Journal of Ethnopharmacology. 2011; 137(2): 1047 |
||Antiulcerogenic activity of Lantana camara leaves on gastric and duodenal ulcers in experimental rats
| ||R. Sathish, Bhushan Vyawahare, K. Natarajan |
| ||Journal of Ethnopharmacology. 2011; 134(1): 195 |