Çimen KARASU, Gülnur TAKE, Deniz ERDOĞAN, Gülten KARABAY

Deneysel diabette probukol uygulanmasının endokrin pankreas dokusuna etkisinin ultrastrüktürel olarak incelenmesi

Bu çalışmada Streptozotosin ile oluşturulan diyabet modellerinde önemli bir antioksidan olan probukolün B hücreleri üzerine koruyucu etkisinin elektron mikroskop düzeyinde incelenmesi amaçlanmıştır. Çalışmada 200 – 250 gr ağırlığında, 7 – 8 haftalık toplam 24 adet erkek sıçan kullanılmış ve 3 grup oluşturulmuştur. 1. grup kontrol (n=8) (sodyum sitrat, i.p., tek doz), 2. grup kronik (8 hafta) diyabet (n=8) (50mg/kg, i.p. tek doz STZ), 3. grup ise diyabet (8 hafta) + probucol tedavisi (300mg/kg/gün, 3 hafta) uygulanan grup (n=8) olarak ayrılmıştır. Süre bitiminde alınan pankreas dokuları LEO 906E Transmission Elektron Mikroskopta değerlendirilmiştir. Yapılan elektron mikroskobik incelemelerde diyabetik grup kontrol grubu ile karşılaştırıldığında, granül sayısının az olduğu, mitokondrion ve Golgi kompleksinde dejeneratif değişikliklerin varlığı gözlenmiştir. Diyabeti izleyen probukol tedavisi sonucunda ise granül sayısının normale yakın olduğu; ancak, organel dejenerasyonunun kısmen de olsa bulunduğu belirlenmiştir. Sonuç olarak, diyabetin B hücrelerinde oluşturduğu dejeneratif değişikliklerin probukol ile azaldığı; ancak, tamamen yok olmadığı belirlenmiştir.

The ultrastructural analysis of the effects of probucol on endocrin pancreas tissue in experimantaly induced diabetes mellitus

The aim of the present study is to investigate the protective effect of probucol, which is an antioxidant agent on beta cells in STZ induced diabetes mellitus model. In this study, 24, 7-8- week -old male rats, weighing 200-250 g were used, and the animals were divided into three groups. The control group received a single dose of sodium citrate (ip, n = 8), the 8 weeks chronic diabetes mellitus group received of a single dose 50 mg/kg STZ (ip, n = 8), the diabetes mellitus group received 300 mg/kg/day probucol for 3 weeks (n = 8). Electron microscopic examination revealed degenerative changes of mitochondria and Golgi complexes in diabetes mellitus group when compared with control group and beta cell granules were relatively decreased. When the samples from the diabetes mellitus group treated with probucol were evaluated, beta cell granule numbers were nearly normal, degeneration in organelle structure was reduced, but still present. As a conclusion probucol decreases the degenerative effects of diabetes mellitus on beta cells, but does not treat them all.

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1. Hand AR, Weiss RE: Effects of streptozotocin-induced diabetes on the rat parotid gland. Lab Invest 1984; 51: 429-40.
2. Burkart V, Kolb H: Protection of islet cells from inflammatory cell death in vitro. Clin Exp Immunol 1993; 93: 273-8.
3. Anderson LC: Effects of alloxan diabetes and insulin in vivo on the rat parotid gland. Am J Physiol 1983; 245: 431-7.
4. De K, Roy K, Saha A: Evaluation of alpha-tocopherol, probucol and ascorbic acid as suppressor of digoxin induced lipid peroxidation. Acta Pol Pharm 2001; 58: 391-400.
5. Heineke EW, Johnson MB, Dilbergen JE: Antioxidant MDL29,311 prevents diabetes in nonobese diabetic and multiple low-dose STZ-injected mice. Diabetes 1993; 42: 1721-30.
6. Kinoshita M: Anti-hyperlipidemic agents. Nippon Rinsho 2002; 60: 974-86.
7. Korchin VI, Lankin VZ, Iarkova RD: Antioxidant probucol prevents development of alloxan diabetes and decrease of antioxidant enzyme activity in rat tissues. Biull Eksp Biol Med 1992; 114: 279-82.
8. Cahrill GF, Jr McDevitt HO: Insulin-dependent diabetes mellitus: The initial lesion. N Engl J Med 1981; 304: 1454-64.
9. Peschke E, Ebelt H, Bromme HJ: “Classical” and “New” diabetogens-comparision of their effects on isolated rat pancreatic islets in vitro. Cell Mol Life Sci 2000; 57: 158-64.
10. Aughsteen AA: An ultrastructural study on the effect of streptozotocin on the islets of Langerhans in mice. J Elect Micros 2000; 49: 681-90.
11. Guz Y, Nasır I, Teitelman G: Regeneration of pancreatic beta cells in an experimental model of diabetes. Endocrinol 2001; 142: 4956-68.
12. Gorogawa S, Kajimoto Y, Umayahara Y: Probucol preserves pancreatic beta-cell function through reduction of oxidative stress in type 2 diabetes. Diabetes Res Clin Pract 2002; 57: 1- 10.
13. Yoshino G, Matsushida M, Maeda E: Effect of probucol on recovery from streptozotocin diabetes in rats. Horm Metab Res 1992; 24: 306-9.
14. Matsushita M, Yoshino G, Iwai M: Protective effect of probucol on alloxan diabetes in rats. Diabetes Res Clin Pract 1989; 7: 313-6.