Lipid Peroksidasyon Oluşumunun Engellenmesi Üzerine Verapamilin Etkisi

Bıı çalışma, karbontetrakloriir CCI4 uygulaması ile lipid peroksidasyon oluşumu ve hücre içi kalsiyum artışını bloke eden verapamil’in lipidperoksidasyonu önleme etkisi araştırılmak amacıyla planlandı. Bunun için toplam 24 adet albino cinsi rat kullanıldı. Ratlar üç gruba ayrıldı. Birinci gruba sadece verapamil 5 mg/kg, i.p. , ikinci gruba sadece CCI4 0.4 ml/kg, s.c. ve iıçüncii gruba ise verapamil uygulandıktan bir saat sonra CCI4 uygulandı. Bu uygulamalar iki gün süre ile tekrarlandı, iki giın sonra rotlardan eter anestezisi altında kan alınarak malondialdehit MDA , rediıkte glutatyon GSH , seruloplazmin ve vitamin C seviyeleri ölçüldü. Karbon tetrakloriir uygulanan ratlarda, malondialdehit miktarı diğer gruplara oranla yüksek bulundu. Gruplar arası karşılaştırma yapıldığında; CCl4 ile verapamil grupları ve CCI4 ile CCl4+verapamil grupları arasında belirgin bir farkın mevcut olduğu ve bunun istatistiki olarak anlamlı olduğu belirlendi P0.05 . Canlı organizmada antioksidan sistemin elemanları olarak bilinen GSH, seruloplazmin ve vitamin C değerleri açısından gruplar arasındaki farkların önemli olmadığı gözlendi P>0.05 . Malondialdehit miktarları göz önüne alındığında, bir kalsiyum kanal blokörii olan verapamilin, CCI4 ile oluşturulan lipid peroksidasyon oluşumunu engelleyebileceği tespit edildi

Anahtar Kelimeler:

Verapamil, Lipid peroksidasyon, Glutatyon, Seruloplazmin, Vitamin C, CCI4

The Effect of Verapamil on Preventioıı of Lipid Peroxidation Formation

The Effect of Verapamil on Preventioıı of Lipid Peroxidation Formation The purpose of this investigation was to fınd out yvhether CCI4 cause lipid peroxidation generation and verapamil ,calcium channel blocker, prevents lipid peroxidation generation. Twenty-four Wistar Albino rats were randomly divided inîo three groups. Following a week adaptation period, the rats in the first group were injected verapamil i.p. ,5 mg/kg , the secoııd group was treated by CCI4 and the third group were treated by verapamil one hour later following CCl4 treatment. Treatment s in ali groııps were repeated t w o consecııtive days. The end of the treatment ,the bloods with EDTA were collected from the hc:ırts under the ether anesthesia. The analyses of MDA, GSH, seruloplasmin and vitamin C were performed. MDA amounts were elevated in the rats treated with only CCI4 in comparison with the other groups. The amount of the MDA yvere statistically differed betvveen CCI4 and verapamil groups and between CCI4 and CCI4 + verapamil groups. Bul the difference were not statistically important between verapamil and CCI4 plus verapamil groups. At the same time, the levels of GSH ,seruloplasmin and vitamin C ,antioxidant system elements,\vere not different among the groups. The results demonstrate that the treatment of verapamil, a Ca2+ channel blocker, was effective in normalizing lipid peroxidation induced by CCI4

Keywords:

Verapamil, Lipid peroxidation, Glutathione, Ascorbic acid, Ceruloplasmin, CCl4,

PDF

___

Erwin JL, Naukam RJ, Rama Saitry BV: Effect of calcium channel blocking agents on calcium and centrilobuler necrosis in the liver of rats treated with hepatotoxic agents, Biochem. Pharmacol. 35 (4): 697-705 (1986).
Itoh S, Shinji G, Shuichi M, Yoshitaka Y: Effect of calcium antagonist diltiazem on liver content and necrosis of hepatocites in rats follovving treatment with CC14, Res. Commun. Chem. Pathol. and Pharmacol. 60 (1): 133-136 (1988).
Morini P, Casalino E, Sblano C, Landriscina C: The responce of rat liver lipid peroxidation, antioxidant enzyme activities and glutathione concentration to the thyroid hormone, Int. J. Biochem. 23 (10): 1025-1030 (1991).
Özdem SS, Şadan G: Serbest oksijen radikallerinin oluşumu ve klinik açıdan önemi, Akd. Ü. Tıp Fak. Derg. 11(1): 63-71 (1994).
Akkuş I: Serbest radikaller ve fızyopatolojik etkileri, Mimoza yayınları, Konya, 1-60, (1995).
Basago HS: Biochemical aspect of free radicals, Biochem. Celi. Biol. 68: 989-998 (1990).
Fu LX, Sjoren KG, Liang QM, Waagstein F, Hoebeke J, Hjalmarson A: Activity of receptors coupled to quanine nucleotide binding regulatory protein in dexorubicin induced cardiomyophaty, Cardivasc. Res. 25(2): 145-150 (1991).
Nayler WG: Basic mechanism involved in the pıotection of the ischaemic myocardium. The role of calcium antagonists, Drugs. 42 (2): 21-2 (1991).
Gupta M, Kale RK: Paradoxical influence of (Ca2+) on lipid peroxidation, Indian. J. Experiment, Biol. 34 (11): 1071-1076 (1996).
Chong X, Rahimtula AD: Alterations in ATP-dependent calcium uptake by rat renal cortex microsomes follovving ochratoxin A administration in vivo or addition in vitro, Biochem. Pharmacol. 44 (7): 1401-9 (1992).
Zhang YM, Zhao DH, Sheng BH: Protective effects of nicorandil on myocardial mitochondria function during ischaemia and reperfusion. Yao. Hsveh. Hsueh. Pao. 26 (2): 144-146. (1991). (Abstrakt).
Gubskii lul, Litvinova NV, Primak RG, Kurskaia N.M: Perekısnoa okislenia lipidov i transport Ca2+ v mikrosomakh pecheri krys pri intoksikatsii khlorofosom ideistvii atropina i verapamila. Ukr. Biokhim. ZH. 66 (1): 73-78 (1994).
Aruoma Ol, Smith C, Cechini R, Evans PS, Halli veli B: Free radical scavenging and inhibition of lipid peroxidation by beta-blockers and by agents that interfere with calcium metabolism.A physiologically-signifıcant process, Biochem. Pharmacol. 42 (4): 735-743 (1991).
Sakaguchi S, Yokota K: Role of Ca2+ on endotoxin-sensitivity by galactosamine challenge lipid peroxide formation and hepatotoxicitiy in zymosan-primed mice, Pharmacol. Toxicol. 77 (2): 81-86 (1995).
Beutler E, Duran O, Kelly BM: Improved method for determination of blood glutathione, J. Lab. & Clin. Med. 61: 882-888( 1963).
Omaye ST, Tumbul Savberlich HE: Selected methods for determination of ascorbic acid in animal cells, tissues, and fluids. Methods in Enzymology. Vol:2, p.7-8(1979).
Yenson, M.: Klinik Biyokimya, İstanbul (1986).
Krinsky NI: Membran antioxidant. Ann. NY. Acat. Sci. 551: 17-31 (1988).
Kayaalp O.: Rasyonel Tedavi Yönünden Tıbbi Farmakoloji. Altıncı Baskı. Cilt:2, Feryal, Matbacılık, Ankara (1992).
Rose S, Thompson KD, Sayeed MM: Ca(2+)-related hepatocellular alterations during intra-abdominal sepsis, Am. J. Physiol. 263(3 Pt 2): R553- R558 (1992).