Protective effects of a calcium channel blocker on apoptosis in thymus of neonatal STZ-diabetic rats


Daǧistanli F. K., Duman B., ÖZTÜRK SEZGİN M.

Acta Histochemica, cilt.107, sa.3, ss.207-214, 2005 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 107 Sayı: 3
  • Basım Tarihi: 2005
  • Doi Numarası: 10.1016/j.acthis.2005.03.005
  • Dergi Adı: Acta Histochemica
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.207-214
  • Anahtar Kelimeler: Apoptosis, Isradipine, Neonatal STZ diabetic rats, Thymus
  • Marmara Üniversitesi Adresli: Hayır

Özet

Streptozotocin (STZ) is known to induce insulin-dependent diabetes in experimental animals. In STZ-induced diabetes, atrophy of the thymus is caused by elevated intracellular calcium levels leading to apoptosis. Hyperglycemia is known to result in a decrease in numbers of T cells in the thymus and circulation. Intracellular calcium levels increase in diabetic animals after induction by STZ. Hyperglycemia inhibits Ca2+-ATPase and increases intracellular calcium levels. We have investigated apoptosis in thymus tissue of neonatal STZ (n-STZ)-diabetic rats and the effects of isradipine as a calcium channel blocker (CCB) on apoptosis. Five groups of newborn Wistar rats were used. On the second day after birth, 100 mg/kg STZ was given i.p. to the first two groups. The first group was n-STZ diabetic. To the second group, starting from the 12th week, 5 mg/kg/day isradipine (i.p) was given for 6 weeks. To the third group, the same dose of isradipine was given on the second day, followed by STZ treatment. The fourth group was non-diabetic and treated with 5 mg/kg/day isradipine for six weeks. The fifth group consisted of non-diabetic rats. To the sixth group, dexamethasone (5 mg/kg i.p.) was given to adult rats. For detection of apoptotic cells in paraffin-embedded thymus sections, the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay was used. The DNA ladder method was performed for analysis of DNA fragmentation. In the isradipine-treated non-diabetic group, typical apoptotic banding patterns were found, whereas thick bands between 123 and 246 bp length were found in the n-STZ- and n-STZ+isradipine-treated groups. More apoptotic cells were observed in the thymus of isradipine-treated, n-STZ-treated and n-STZ+isradipine-treated groups when compared with the non-diabetic control and isradipine+n-STZ-treated groups. In conclusion, we observed that long-term STZ diabetes results in apoptosis in the thymus. We also found that isradipine administered before STZ has protective effects against apoptosis, whereas isradipine alone induces apoptosis. © 2005 Elsevier GmbH. All rights reserved.