NTI-ULCEROGENIC EFFECT OF GENISTEIN AGAINST INDOMETHACIN-INDUCED GASTRIC ULCER IN RATS

Authors

  • IHAB T ABDEL-RAHEEM Department of Pharmacology and Toxicology, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt;
  • GHAZI A BAMAGOUS
  • Gamal A Omran

Abstract

ABSTRACT
Objectives: Free radicals generation, inflammation, and nitric oxide (NO) modulation are involved in indomethacin (IND)-induced gastric ulcers.
Most of the drugs used for the treatment of gastric ulcer have various side effects. Genistein (GEN), the natural isoflavones isolated from soya bean
has an antioxidant, anti-inflammatory, and NO modulating activity. These properties could make GEN a promising and safe, natural candidate against
IND-induced peptic ulcers.
Methods: Rats were divided into four groups. Control group; GEN group (10 mg/kg, p.o.); IND group (48 mg/kg, orally); and GEN+IND group (GEN
administered 1 week before IND injection). 6 hrs after IND administration, all rats were sacrificed. Gastric juice acidity and gastric injury were
evaluated directly. The levels of tumor necrosis factor alpha (TNF-α), myeloperoxidase (MPO), and NO were determined in gastric tissues. Moreover,
glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) activity were determined in mucosal tissues.
Results: Several mechanisms are involved in IND-induced ulcers as evidenced from the increase in TNF-α, MPO, and reduction in NO levels. In addition,
free radicals also participate in the pathogenesis as evidenced from the increase in MDA levels and reduction in GSH levels and SOD activity. On the
other hand, pre-administration of GEN markedly attenuated IND-induced ulcers without affecting gastric acidity, through a reduction of the elevated
TNF-α and MPO levels. Moreover, GEN significantly restored the declined NO level and ameliorated the unbalanced oxidative stress parameters.
Conclusion: GEN markedly protects against IND-induced ulcers as revealed from biochemical data and amelioration of IND-induced lesions.
Therefore, GEN may be a promising candidate for protection against IND-induced gastropathy.
Keywords: Genistein, Ulcers, Indomethacin, Nitric oxide, Myeloperoxidase, Tumor necrosis factor alpha.

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Author Biography

IHAB T ABDEL-RAHEEM, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt;

Department of Pharmacology and Toxicology

References

REFERENCES

Yuan Y, Padol IT, Hunt RH. Peptic ulcer disease today. Nat Clin Pract

Gastroenterol Hepatol 2006;3(2):80-9.

Araújo MB, Borini P, Guimarães RC. Etiopathogenesis of peptic ulcer:

Back to the past? Arq Gastroenterol 2014;51(2):155-61.

Lima ZP, Severi JA, Pellizzon CH, Brito AR, Solis PN, Cáceres A, et al.

Can the aqueous decoction of mango flowers be used as an antiulcer

agent? J Ethnopharmacol 2006;106(1):29-37.

Belaiche J, Burette A, De Vos M, Louis E, Huybrechts M, Deltenre M;

Belgian Study Group of NSAID-GI Complications. Observational

survey of NSAID-related upper gastro-intestinal adverse events in

Belgium. Acta Gastroenterol Belg 2002;65(2):65-73.

Dhiyaaldeen SM, Amin ZA, Darvish PH, Mustafa IF, Jamil MM,

Rouhollahi E, et al. Protective effects of (1-(4-hydroxy-phenyl)-3m-tolyl-propenone

chalcone

in

indomethacin-induced gastric

erosive

damage

in rats. BMC Vet

Res 2014;10(6):961.

Abbas AM, Sakr HF. Effect of selenium and grape seed extract on

indomethacin-induced gastric ulcers in rats. J Physiol Biochem

;69(3):527-37.

Mitra RS, Shimizu Y, Nickoloff BJ. Histamine and cis-urocanic

acid augment tumor necrosis factor-alpha mediated induction of

keratinocyte intercellular adhesion molecule-1 expression. J Cell

Physiol 1993;156(2):348-57.

Appleyard CB, McCafferty DM, Tigley AW, Swain MG, Wallace JL.

Tumor necrosis factor mediation of NSAID-induced gastric damage:

Role of leukocyte adherence. Am J Physiol 1996;270:G42-8.

Handa O, Majima A, Onozawa Y, Horie H, Uehara Y, Fukui A, et al.

The role of mitochondria-derived reactive oxygen species in the

pathogenesis of non-steroidal anti-inflammatory drug-induced small

intestinal injury. Free Radic Res 2014;48(9):1095-9.

Slomiany BL, Slomiany A. Role of endothelin-converting enzyme-1 in

the suppression of constitutive nitric oxide synthase in rat gastric mucosal

injury by indomethacin. Scand J Gastroenterol 2000;35(2):1131-6.

Vitale DC, Piazza C, Melilli B, Drago F, Salomone S. Isoflavones:

Estrogenic activity, biological effect and bioavailability. Eur J Drug

Metab Pharmacokinet 2013;38(30):15-25.

Saleh DO, Abdel Jaleel GA, El-Awdan SA, Oraby F, Badawi M.

Thioacetamide-induced liver injury: Protective role of genistein. Can J

Physiol Pharmacol 2014;92(11):965-73.

Xiang Q, Lin G, Fu X, Wang S, Wang T. The role of peroxisome

proliferator-activated receptor-gamma and estrogen receptors in

genistein-induced regulation of vascular tone in female rat aortas.

Pharmacology 2010;86(2):117-24.

Squadrito F, Altavilla D, Morabito N, Crisafulli A, D’Anna R,

Corrado F, et al. The effect of the phytoestrogen genistein on plasma

Asian J Pharm Clin Res, Vol 9, Issue 2, 2016, 58-63

Abdel-Raheem et al.

nitric oxide concentrations, endothelin-1 levels and endothelium

dependent vasodilation in postmenopausal women. Atherosclerosis

;163(2):339-47.

D’Anna R, Baviera G, Corrado F, Cancellieri F, Crisafulli A,

Squadrito F. The effect of the phytoestrogen genistein and hormone

replacement therapy on homocysteine and C-reactive protein level in

postmenopausal women. Acta Obstet Gynecol Scand 2005;84(5):474-7.

Gong DK, Liu BH, Tan XH. Genistein prevents cadmium-induced

neurotoxic effects through its antioxidant mechanisms. Drug Res

(Stuttg) 2015;65(2):65-9.

Zhang X, Tajima K, Kageyama K, Kyoi T. Irsogladine maleate

suppresses indomethacin-induced elevation of proinflammatory

cytokines and gastric injury in rats. World J Gastroenterol

;14(30):4784-90.

Rajashekhara N, Ashok BK, Sharma PP, Ravishankar B. The evaluation

of anti-ulcerogenic effect of rhizome starch of two source plants of

Tugaksheeree (Curcuma angustifolia Roxb. and Maranta arundinacea

Linn.) on pyloric ligated rats. Ayu 2014;35(2):191-7.

Al Asmari AK, Al Omani S, Elfaki I, Tariq M, Al Malki A, Al Asmary S.

Gastric antisecretory and antiulcer activity of bovine hemoglobin.

World J Gastroenterol 2013;19(2):3291-9.

Bancroft J, Stevens A. In: Stevens A, editors. Theory and Practice of

Histological Techniques. New York: Churchill Livingstone; 1982.

p. 188-90.

Park JM, Han YM, Kangwan N, Lee SY, Jung MK, Kim EH, et al.

S-allyl cysteine alleviates nonsteroidal anti-inflammatory drug-induced

gastric mucosal damages by increasing cyclooxygenase-2 inhibition,

heme oxygenase-1 induction, and histone deacetylation inhibition.

J Gastroenterol Hepatol 2014;29 Suppl 4:80-92.

Sabiu S, Garuba T, Sunmonu TO, Sulyman AO, Ismail NO.

Indomethacin-induced gastric ulceration in rats: Ameliorative roles of

Spondias mombin and Ficus exasperata. Pharm Biol 2015;27:1-7.

Choi YJ, Kim N, Lee JY, Nam RH, Chang H, Seo JH, et al. Protective

effects of garlic extract, PMK-S005, against nonsteroidal antiinflammatory

drugs-induced

acute

gastric

damage

in

rats. Dig

Dis Sci

;59(12):2927-34.

Moustafa YM, Khoder DM, El-Awady EE, Zaitone SA. Sildenafil citrate

protects against gastric mucosal damage induced by indomethacin in

rats. Eur Rev Med Pharmacol Sci 2013;17(2):179-88.

Albayrak A, Alp HH, Suleyman H. Investigation of antiulcer

and antioxidant activity of moclobemide in rats. Eurasian J Med

;47(1):32-40.

Gomathy G, Venkatesan D, Palani S. Gastroprotective potentials of

the ethanolic extract of Mukia maderaspatana against indomethacininduced

gastric ulcer in rats. Nat Prod Res 2015;29(22):2107-11.

Kaplan KA, Odabasoglu F, Halici Z, Halici M, Cadirci E, Atalay F,

et al. Alpha-lipoic acid protects against indomethacin-induced gastric

oxidative toxicity by modulating antioxidant system. J Food Sci

;77(11):H224-30.

Saha S, Sadhukhan P, Sil PC. Genistein: A Phytoestrogen with

multifaceted therapeutic properties. Mini Rev Med Chem 2014.

Behloul N, Wu G. Genistein: A promising therapeutic agent for obesity

and diabetes treatment. Eur J Pharmacol 2013;698(1-3):31-8.

Jeong JW, Lee HH, Han MH, Kim GY, Kim WJ, Choi YH. Antiinflammatory

effects

of genistein via

suppression

of the toll-like

receptor

-mediated

signaling

pathway

in

lipopolysaccharide-stimulated

BV2

microglia.

Chem Biol Interact 2014;212:30-9.

Ganai AA, Khan AA, Malik ZA, Farooqi H. Genistein modulates

the expression of NF-?B and MAPK (p-38 and ERK1/2), thereby

attenuating d-Galactosamine induced fulminant hepatic failure in

Wistar rats. Toxicol Appl Pharmacol 2015;283(2):139-46.

Mullane KM, Kraemer R, Smith B. Myeloperoxidase activity as

a quantitative assessment of neutrophil infiltration into ischemic

myocardium. J Pharmacol Methods 1985;14:157-67.

Seibel J, Molzberger AF, Hertrampf T, Laudenbach-Leschowski U,

Diel P. Oral treatment with genistein reduces the expression of molecular

and biochemical markers of inflammation in a rat model of chronic

TNBS-induced colitis. Eur J Nutr 2009;48(4):213-20.

Wang R, Tu J, Zhang Q, Zhang X, Zhu Y, Ma W, et al. Genistein

attenuates ischemic oxidative damage and behavioral deficits via

eNOS/Nrf2/HO-1 signaling. Hippocampus 2013;23(7):634-47.

Javanbakht MH, Sadria R, Djalali M, Derakhshanian H,

Hosseinzadeh P, Zarei M, et al. Soy protein and genistein improves

renal antioxidant status in experimental nephrotic syndrome. Nefrologia

;34(4):483-90.

Ibrahim WH, Habib HM, Chow CK, Bruckner GG. Isoflavone-rich soy

isolate reduces lipid peroxidation in mouse liver. Int J Vitam Nutr Res

;78(4-5):217-22.

Published

01-03-2016

How to Cite

ABDEL-RAHEEM, I. T. ., G. A. . BAMAGOUS, and G. A. Omran. “NTI-ULCEROGENIC EFFECT OF GENISTEIN AGAINST INDOMETHACIN-INDUCED GASTRIC ULCER IN RATS”. Asian Journal of Pharmaceutical and Clinical Research, vol. 9, no. 2, Mar. 2016, pp. 58-63, https://mail.innovareacademics.in/journals/index.php/ajpcr/article/view/9048.

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