메뉴 건너뛰기




Volumn 8, Issue 2, 2012, Pages 115-121

The effect of lacidipine on indomethacin induced ulcers in Rats

Author keywords

Indomethacin; Lacidipine; Oxidant and antioxidant parameters; Rat; Ulcer

Indexed keywords

FAMOTIDINE; GLUTATHIONE; GLUTATHIONE PEROXIDASE; INDOMETACIN; LACIDIPINE; MALONALDEHYDE; MYELOPEROXIDASE; PROSTAGLANDIN; SUPEROXIDE DISMUTASE;

EID: 84858013354     PISSN: 18117775     EISSN: 18125700     Source Type: Journal    
DOI: 10.3923/ijp.2012.115.121     Document Type: Article
Times cited : (9)

References (42)
  • 1
    • 0020619638 scopus 로고
    • Effect of verapamil on gastric secretion in man
    • Aadland, E. and A. Berstad, 1983. Effect of verapamil on gastric secretion in man. Scand. J. Gastr., 18: 969-971.
    • (1983) Scand. J. Gastr , vol.18 , pp. 969-971
    • Aadland, E.1    Berstad, A.2
  • 2
    • 80055091801 scopus 로고    scopus 로고
    • Antiulcer effects of alpha lipoic acid on gastric acid secretion and mucosal defense factors in rats
    • Abd El-Kader, M.A., M.M. Ah, N.M. El-Sammad and M.A. El-Shaer, 2011. Antiulcer effects of alpha lipoic acid on gastric acid secretion and mucosal defense factors in rats. Asian J. Biochem., 6: 426-438.
    • (2011) Asian J. Biochem , vol.6 , pp. 426-438
    • Abd-El-Kader, M.A.1    Ah, M.M.2    El-Sammad, N.M.3    El-Shaer, M.A.4
  • 3
    • 84858028074 scopus 로고    scopus 로고
    • Comparison of the effects of low protein diet versus chemical neurotoxins on brain weight, brain lipid peroxidation and antioxidant status of rats
    • Adebayo, O.L., B.O. Adegbesan and G.A. Adenuga, 2009. Comparison of the effects of low protein diet versus chemical neurotoxins on brain weight, brain lipid peroxidation and antioxidant status of rats. Asian J. Biol. Sci.,2: 7-13.
    • (2009) Asian J. Biol. Sci , vol.2 , pp. 7-13
    • Adebayo, O.L.1    Adegbesan, B.O.2    Adenuga, G.A.3
  • 4
    • 0026742483 scopus 로고
    • Indomethacin-induced leukocyte adhesion in mesenteric venules: Role of lipoxygenase products
    • Asako, H., P. Kubes, J. Wallace, T. Gaginella, R.E. Wolf and D.N. Granger, 1992. Indomethacin-induced leukocyte adhesion in mesenteric venules: Role of lipoxygenase products. Am. J. Physiol., 262: 903-908.
    • (1992) Am. J. Physiol , vol.262 , pp. 903-908
    • Asako, H.1    Kubes, P.2    Wallace, J.3    Gaginella, T.4    Wolf, R.E.5    Granger, D.N.6
  • 5
    • 0029966043 scopus 로고    scopus 로고
    • Intracellular neutrophil myeloperoxidase is reduced in unstable angina and acute myocardial infarction but its reduction is not related to ischemia
    • Biasucci, L.M., G. D'Onofrio, G. Liuzzo, G. Zini and C. Monaco et al., 1996. Intracellular neutrophil myeloperoxidase is reduced in unstable angina and acute myocardial infarction but its reduction is not related to ischemia. J. Am. Coll. Cardiol., 27: 611-616.
    • (1996) J. Am. Coll. Cardiol , vol.27 , pp. 611-616
    • Biasucci, L.M.1    D'onofrio, G.2    Liuzzo, G.3    Zini, G.4    Monaco, C.5
  • 6
    • 67649726840 scopus 로고    scopus 로고
    • Antiulcer activity of fluvoxamine in rats and its effect on oxidant and antioxidant parameters in stomach tissue
    • Dursun, H., M. Bilici, F. Albayrak, C. Ozturk, M.B. Saglam, H.H. Alp and H. Suleyman, 2009. Antiulcer activity of fluvoxamine in rats and its effect on oxidant and antioxidant parameters in stomach tissue. BMC Gastroenterol, 9: 36-36.
    • (2009) BMC Gastroenterol , vol.9 , pp. 36
    • Dursun, H.1    Bilici, M.2    Albayrak, F.3    Ozturk, C.4    Saglam, M.B.5    Alp, H.H.6    Suleyman, H.7
  • 7
    • 0023265015 scopus 로고
    • Calcium channel blockers protect against efhanol and indomethacin-induced gastric lesions in rats
    • Ghanayem, B.I., H.B. Matthews and R.R. Maronpot, 1987. Calcium channel blockers protect against efhanol and indomethacin-induced gastric lesions in rats. Gastroenterology, 92: 106-111.
    • (1987) Gastroenterology , vol.92 , pp. 106-111
    • Ghanayem, B.I.1    Matthews, H.B.2    Maronpot, R.R.3
  • 8
    • 76449122383 scopus 로고    scopus 로고
    • Pro-ulcer effects of resveratrol in mice with indomethacin-induced gastric ulcers are reversed by L-arginine
    • Guha, P., A. Dey, A. Chatterjee, S. Chattopadhyay and S.K. Bandyopadhyay, 2010. Pro-ulcer effects of resveratrol in mice with indomethacin-induced gastric ulcers are reversed by L-arginine. Br. J. Pharmacol., 159: 726-734.
    • (2010) Br. J. Pharmacol , vol.159 , pp. 726-734
    • Guha, P.1    Dey, A.2    Chatterjee, A.3    Chattopadhyay, S.4    Bandyopadhyay, S.K.5
  • 9
    • 0038641236 scopus 로고    scopus 로고
    • Endothelial dysfunction, hypertension and atherosclerosis. A review of the effects of lacidipine
    • Haller, H., F. Cosenfmo and T.F. Luscher, 2002. Endothelial dysfunction, hypertension and atherosclerosis. A review of the effects of lacidipine. Drugs RD, 3: 311-323.
    • (2002) Drugs RD , vol.3 , pp. 311-323
    • Haller, H.1    Cosenfmo, F.2    Luscher, T.F.3
  • 10
    • 0032455171 scopus 로고    scopus 로고
    • Role of antioxidants in gastric mucosal damage induced by indomethacin in rats
    • Hassan, A., E. Martin and P. Puig-Parellada, 1998. Role of antioxidants in gastric mucosal damage induced by indomethacin in rats. Meth. Find Exp. Clin. Pharmacol., 20: 849-854.
    • (1998) Meth. Find Exp. Clin. Pharmacol , vol.20 , pp. 849-854
    • Hassan, A.1    Martin, E.2    Puig-Parellada, P.3
  • 11
    • 0021951017 scopus 로고
    • Role of oxygen-derived free radicals in hemorrhagic shock-induced gastric lesions in the rat
    • Itoh, M. and P.H. Guth, 1985. Role of oxygen-derived free radicals in hemorrhagic shock-induced gastric lesions in the rat. Gastroenterology, 88: 1162-1167.
    • (1985) Gastroenterology , vol.88 , pp. 1162-1167
    • Itoh, M.1    Guth, P.H.2
  • 12
    • 65649108024 scopus 로고    scopus 로고
    • The effects of methanol extract oihobaria pulmonaria, a lichen species, on indometacin-induced gastric mucosal damage, oxidative stress and neutrophil infiltration
    • Karakus, B., F. Odabasoglu, A. Cakir, Z. Halici, Y. Bayir, M. Halici, A. Asian and H. Suleyman, 2009. The effects of methanol extract oihobaria pulmonaria, a lichen species, on indometacin-induced gastric mucosal damage, oxidative stress and neutrophil infiltration. Phytother. Res., 23: 635-639.
    • (2009) Phytother. Res , vol.23 , pp. 635-639
    • Karakus, B.1    Odabasoglu, F.2    Cakir, A.3    Halici, Z.4    Bayir, Y.5    Halici, M.6    Asian, A.7    Suleyman, H.8
  • 13
    • 0030035210 scopus 로고    scopus 로고
    • Sulphydryl blocker induced gastric damage is ameliorated by scavenging of free radicals
    • Karmeli, F., E. Okon and D. Rachmilewitz, 1996. Sulphydryl blocker induced gastric damage is ameliorated by scavenging of free radicals. Gut, 38: 826-831.
    • (1996) Gut , vol.38 , pp. 826-831
    • Karmeli, F.1    Okon, E.2    Rachmilewitz, D.3
  • 15
    • 80052778137 scopus 로고    scopus 로고
    • The role of a-2 adrenergic receptors in the anti-ulcerative activity of famotidine and omeprazole in rats and its relationship with oxidant-antioxidant parameters
    • Kisaoglu, A., B. Ozogul, N. Cetyn, B. Suleyman, S. Atamanalp, F. Akcay and H. Suleyman, 2011. The role of a-2 adrenergic receptors in the anti-ulcerative activity of famotidine and omeprazole in rats and its relationship with oxidant-antioxidant parameters. Int. J. Pharmacol., 7: 682-689.
    • (2011) Int. J. Pharmacol , vol.7 , pp. 682-689
    • Kisaoglu, A.1    Ozogul, B.2    Cetyn, N.3    Suleyman, B.4    Atamanalp, S.5    Akcay, F.6    Suleyman, H.7
  • 16
    • 0017067418 scopus 로고
    • Glutathione peroxidase activity in selenium-deficient rat liver
    • Lawrence, R.A. and R.F. Burk, 1976. Glutathione peroxidase activity in selenium-deficient rat liver. Biochem. Res. Commun, 71: 952-958.
    • (1976) Biochem. Res. Commun , vol.71 , pp. 952-958
    • Lawrence, R.A.1    Burk, R.F.2
  • 17
    • 78649366895 scopus 로고    scopus 로고
    • A systematic review on oxidant/antioxidant imbalance in aluminum toxicity
    • Mohammadirad, A. and M. Abdollahi, 2011. A systematic review on oxidant/antioxidant imbalance in aluminum toxicity. Int. J. Pharmacol., 7: 12-21.
    • (2011) Int. J. Pharmacol , vol.7 , pp. 12-21
    • Mohammadirad, A.1    Abdollahi, M.2
  • 18
    • 0027373821 scopus 로고
    • Role of oxygen radicals in indomethacin-induced gastric mucosal microvascular injury in rats
    • Naito, Y., T. Yoshikawa, T. Kaneko, S. Iinuma and S. Nishimura et al, 1993. Role of oxygen radicals in indomethacin-induced gastric mucosal microvascular injury in rats. J. Clin. Gastroenterol., 17: S99-S103.
    • (1993) J. Clin. Gastroenterol , vol.17
    • Naito, Y.1    Yoshikawa, T.2    Kaneko, T.3    Iinuma, S.4    Nishimura, S.5
  • 19
    • 0023833487 scopus 로고
    • Protection by the calcium antagonist Wy-47,037 against stress ulceration in the rat
    • Nielsen, S.T. and T.S. Sulkowski, 1988. Protection by the calcium antagonist Wy-47,037 against stress ulceration in the rat. Pharmacol. Biochem. Behav., 29: 129-132.
    • (1988) Pharmacol. Biochem. Behav , vol.29 , pp. 129-132
    • Nielsen, S.T.1    Sulkowski, T.S.2
  • 20
    • 48849105515 scopus 로고    scopus 로고
    • Beneficial effects of vegetable oils corn, olive and sunflower oils and alphatocopherol on anti-inflammatory and gastrointestinal profiles of indomethacin in rats
    • Odabasoglu, F., Z. Halici, A. Cakir, M. Halici and H. Aygun et al, 2008. Beneficial effects of vegetable oils corn, olive and sunflower oils and alphatocopherol on anti-inflammatory and gastrointestinal profiles of indomethacin in rats. Eur. J. Pharmacol., 591: 300-306.
    • (2008) Eur. J. Pharmacol , vol.591 , pp. 300-306
    • Odabasoglu, F.1    Halici, Z.2    Cakir, A.3    Halici, M.4    Aygun, H.5
  • 21
    • 84856061154 scopus 로고    scopus 로고
    • The salutary role of Allium cepa extract on the liver histology, liver oxidative status and liver marker enzymes of rabbits submitted to alcohol-induced toxicity
    • Ogunlade, B., L.C. Saalu, O.S. Ogunmodede, G.G. Akunna, O.A. Adeeyo and G.O. Ajayi, 2012. The salutary role of Allium cepa extract on the liver histology, liver oxidative status and liver marker enzymes of rabbits submitted to alcohol-induced toxicity. Am. J. Biochem. Mol. Biol, 2: 67-81.
    • (2012) Am. J. Biochem. Mol. Biol , vol.2 , pp. 67-81
    • Ogunlade, B.1    Saalu, L.C.2    Ogunmodede, O.S.3    Akunna, G.G.4    Adeeyo, O.A.5    Ajayi, G.O.6
  • 22
    • 0018384650 scopus 로고
    • Assay for lipid peroxides in animal tissues by fhiobarbituric acid reaction
    • Ohkawa, H., N. Ohishi and K. Yagi, 1979. Assay for lipid peroxides in animal tissues by fhiobarbituric acid reaction. Anal. Biochem., 95: 351-358.
    • (1979) Anal. Biochem , vol.95 , pp. 351-358
    • Ohkawa, H.1    Ohishi, N.2    Yagi, K.3
  • 23
    • 33745757376 scopus 로고    scopus 로고
    • Potentiation of gastric ulceration by experimental lead exposure in rats
    • Olaleye, S.B., Y. Raji, S.A. Onasanwo, P. Erigbali and S.O. Oyesola et al, 2006. Potentiation of gastric ulceration by experimental lead exposure in rats. J. Biol. Sci., 6: 480-484.
    • (2006) J. Biol. Sci , vol.6 , pp. 480-484
    • Olaleye, S.B.1    Raji, Y.2    Onasanwo, S.A.3    Erigbali, P.4    Oyesola, S.O.5
  • 24
    • 70349337303 scopus 로고    scopus 로고
    • Effect of methanohc extract of Pongamia pinnata Linn, seed on gastroduodenal ulceration and mucosal offensive and defensive factors in rats
    • Prabha, T., M. Dorababu, S. Goel, P.K. Agarwal, A. Singh, V.K. Joshi and R.K. Goel, 2009. Effect of methanohc extract of Pongamia pinnata Linn, seed on gastroduodenal ulceration and mucosal offensive and defensive factors in rats. Indian J. Exp Biol, 47: 649-659.
    • (2009) Indian J. Exp Biol , vol.47 , pp. 649-659
    • Prabha, T.1    Dorababu, M.2    Goel, S.3    Agarwal, P.K.4    Singh, A.5    Joshi, V.K.6    Goel, R.K.7
  • 25
    • 33646174737 scopus 로고    scopus 로고
    • Protective effects of Polygonum viviparum L. root and its extracts against lipid-peroxidation induced by indomethacin in Rats
    • Rifat-uz-Zaman, M.S. Akhtar and M.S. Khan, 2005. Protective effects of Polygonum viviparum L. root and its extracts against lipid-peroxidation induced by indomethacin in Rats. Int. J. Pharmacol., 1: 324-328.
    • (2005) Int. J. Pharmacol , vol.1 , pp. 324-328
    • Rifat-uz-Zaman1    Akhtar, M.S.2    Khan, M.S.3
  • 26
    • 84858041868 scopus 로고    scopus 로고
    • Therapeutic efficacy of Indian ayurvedic herbal formulation triphala on lipid peroxidation, antioxidant status and inflammatory mediator TNF- a in adjuvant-induced arthritic mice
    • Sabina, E.P. and M. Rasool, 2007. Therapeutic efficacy of Indian ayurvedic herbal formulation triphala on lipid peroxidation, antioxidant status and inflammatory mediator TNF- a in adjuvant-induced arthritic mice. Int. J. Biol. Chem., 1: 149-155.
    • (2007) Int. J. Biol. Chem , vol.1 , pp. 149-155
    • Sabina, E.P.1    Rasool, M.2
  • 27
    • 0028120948 scopus 로고
    • Scavenging free radicals to prevent stress induced gastric mucosal injury
    • Salim, A.S., 1994. Scavenging free radicals to prevent stress induced gastric mucosal injury. J. Surg. Res., 56: 45-52.
    • (1994) J. Surg. Res , vol.56 , pp. 45-52
    • Salim, A.S.1
  • 28
    • 0014428865 scopus 로고
    • Estimation of total, protein-bound and nonprotein sulfhydryl groups in tissue with Ellman's reagent
    • Sedlak, J. and R.H. Lindsay, 1968. Estimation of total, protein-bound and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal. Biochem., 25: 192-205.
    • (1968) Anal. Biochem , vol.25 , pp. 192-205
    • Sedlak, J.1    Lindsay, R.H.2
  • 29
    • 0035080516 scopus 로고    scopus 로고
    • Protective effect of famotidine, omeprazole and melatonin against acetylsalicylic acid-induced gastric damage in rats
    • Sener-Muratoglu, G., K. Paskaloglu, S. Arbak, C. Hurdag and G. Ayanoglu-Dulger, 2001. Protective effect of famotidine, omeprazole and melatonin against acetylsalicylic acid-induced gastric damage in rats. Dig. Dis. Sci.,46: 318-330.
    • (2001) Dig. Dis. Sci , vol.46 , pp. 318-330
    • Sener-Muratoglu, G.1    Paskaloglu, K.2    Arbak, S.3    Hurdag, C.4    Ayanoglu-Dulger, G.5
  • 30
    • 0020525162 scopus 로고
    • Calcium channel antagonists verapamil and gallopamil are powerful inhibitors of acid secretion in isolated and enriched guinea pig parietal cells
    • Sewing, K.F. and H. Hannemann, 1983. Calcium channel antagonists verapamil and gallopamil are powerful inhibitors of acid secretion in isolated and enriched guinea pig parietal cells. Pharmacology, 27: 9-14.
    • (1983) Pharmacology , vol.27 , pp. 9-14
    • Sewing, K.F.1    Hannemann, H.2
  • 31
    • 67349164054 scopus 로고    scopus 로고
    • Comparative study on the gastroprotective potential of some antidepressants in indomethacin-induced ulcer in rats
    • Suleyman, H., E. Cadirci, A. Albayrak, B. Polat and Z. Halicie, et al., 2009. Comparative study on the gastroprotective potential of some antidepressants in indomethacin-induced ulcer in rats. Chem. Biol. Interact, 180: 318-324.
    • (2009) Chem. Biol. Interact , vol.180 , pp. 318-324
    • Suleyman, H.1    Cadirci, E.2    Albayrak, A.3    Polat, B.4    Halicie, Z.5
  • 32
    • 77956184396 scopus 로고    scopus 로고
    • Different mechanisms in formation and prevention of indomethacin-induced gastric ulcers
    • Suleyman, H., A. Albayrak, M. Bilici, E. Cadirci and Z. Halici, 2010. Different mechanisms in formation and prevention of indomethacin-induced gastric ulcers. Inflammation, 33: 224-234.
    • (2010) Inflammation , vol.33 , pp. 224-234
    • Suleyman, H.1    Albayrak, A.2    Bilici, M.3    Cadirci, E.4    Halici, Z.5
  • 33
    • 0023952554 scopus 로고
    • A simple method for clinical assay of superoxide dismutase
    • Sun, Y., L. W. Oberley and Y. Li, 1988. A simple method for clinical assay of superoxide dismutase. Clin. Chem., 34: 497-500.
    • (1988) Clin. Chem , vol.34 , pp. 497-500
    • Sun, Y.1    Oberley, L.W.2    Li, Y.3
  • 34
    • 0022006479 scopus 로고
    • Early vascular injury and increased vascular permeability in gastric mucosal injury caused by ethanol in the rat
    • Szabo, S., J.S. Trier, A. Brown and J. Schnoor, 1985. Early vascular injury and increased vascular permeability in gastric mucosal injury caused by ethanol in the rat. Gastroenterology, 88: 228-236.
    • (1985) Gastroenterology , vol.88 , pp. 228-236
    • Szabo, S.1    Trier, J.S.2    Brown, A.3    Schnoor, J.4
  • 35
    • 0029921770 scopus 로고    scopus 로고
    • Diethyldithiocarbamate, a superoxide dismutase inhibitor, reduces indomethacin-induced gastric lesions in rats
    • Takeuchi, K., K. Takehara and T. Ohuchi, 1996. Diethyldithiocarbamate, a superoxide dismutase inhibitor, reduces indomethacin-induced gastric lesions in rats. Digestion, 57: 201-209.
    • (1996) Digestion , vol.57 , pp. 201-209
    • Takeuchi, K.1    Takehara, K.2    Ohuchi, T.3
  • 36
    • 0025977064 scopus 로고
    • The biological significance of malondialdehyde determination in the assessment of tissue oxidative stress
    • Valenzuela, A., 1991. The biological significance of malondialdehyde determination in the assessment of tissue oxidative stress. Life Sci., 48: 301-309.
    • (1991) Life Sci , vol.48 , pp. 301-309
    • Valenzuela, A.1
  • 37
    • 77749251826 scopus 로고    scopus 로고
    • Anti-ulcer role of herbomineral siddha drug-thamira parpam on experimentally induced gastric mucosal damage in rats
    • Vasanthkumar, M., R.P. Parameswari, V. Vijaya Kumar and M.K. Sangeetha, et al. 2010. Anti-ulcer role of herbomineral siddha drug-thamira parpam on experimentally induced gastric mucosal damage in rats. Hum. Exp. Toxicol., 29: 161-173.
    • (2010) Hum. Exp. Toxicol , vol.29 , pp. 161-173
    • Vasanthkumar, M.1    Parameswari, R.P.2    Vijaya, K.V.3    Sangeetha, M.K.4
  • 38
    • 0028894060 scopus 로고
    • Nitric oxide-induced cytotoxicity: Involvement of cellular resistance to oxidative stress and the role of glutathione in protection
    • Walker, M.W., M.T. Kmter, R.J. Roberts and D.R. Spitz, 1995. Nitric oxide-induced cytotoxicity: involvement of cellular resistance to oxidative stress and the role of glutathione in protection. Pediatr. Res., 37: 41-49.
    • (1995) Pediatr. Res , vol.37 , pp. 41-49
    • Walker, M.W.1    Kmter, M.T.2    Roberts, R.J.3    Spitz, D.R.4
  • 39
    • 0025941759 scopus 로고
    • In vivo formation of oxidized DNA bases in tumor promoter-treated mouse skin
    • Wei, H. and K. Frenkel, 1991. In vivo formation of oxidized DNA bases in tumor promoter-treated mouse skin. Cancer Res., 51: 4443-4449.
    • (1991) Cancer Res , vol.51 , pp. 4443-4449
    • Wei, H.1    Frenkel, K.2
  • 40
    • 55449119185 scopus 로고    scopus 로고
    • Irsogladine maleate suppresses indomethacininduced elevation of proinflammatory cytokines and gastric injury in rats
    • Zhang, X., K. Tajima, K. Kageyama and T. Kyoi, 2008. Irsogladine maleate suppresses indomethacininduced elevation of proinflammatory cytokines and gastric injury in rats. World J. Gastroenterol., 14: 4784-4790.
    • (2008) World J. Gastroenterol , vol.14 , pp. 4784-4790
    • Zhang, X.1    Tajima, K.2    Kageyama, K.3    Kyoi, T.4
  • 41
    • 66549122012 scopus 로고    scopus 로고
    • Protective effects of DIDS against ethanolinduced gastric mucosal injury in rats
    • Zhao, W., F. Zhu, W. Shen, A. Fu and L. Zheng et al., 2009. Protective effects of DIDS against ethanolinduced gastric mucosal injury in rats. Acta Biochim. Biophys. Sin (Shanghai), 41: 301-308.
    • (2009) Acta Biochim. Biophys. Sin (Shanghai) , vol.41 , pp. 301-308
    • Zhao, W.1    Zhu, F.2    Shen, W.3    Fu, A.4    Zheng, L.5
  • 42
    • 77953828884 scopus 로고    scopus 로고
    • Gastric acid is the key modulator in the pathogenesis of non-steroidal anti-inflammatory drug-induced ulceration in rats
    • Zinkievich, J.M., S. George, S. Jha, J. Nandi and R. A. Levine, 2010. Gastric acid is the key modulator in the pathogenesis of non-steroidal anti-inflammatory drug-induced ulceration in rats. Clin. Exp. Pharmacol. Physiol, 37: 654-661.
    • (2010) Clin. Exp. Pharmacol. Physiol , vol.37 , pp. 654-661
    • Zinkievich, J.M.1    George, S.2    Jha, S.3    Nandi, J.4    Levine, R.A.5


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.