Nitric oxide (NO) and caspase-8 in liver streptozotocin-induced diabetic rats

INGARAMO PI; RONCO M.T; FRANCÉS D; GALLEANO M,; MONTI, J.A; CEBALLOS MP; CARRILLO M.C; CARNOVALE CE

Chile

Congreso; VI Meeting of SFRBM-South American Group.; 2009

Society for Free Radical Research Biology and Medicine

&amp;amp;lt;!-- /* Font Definitions */ @font-face {font-family:Tahoma; panose-1:2 11 6 4 3 5 4 4 2 4; mso-font-charset:0; mso-generic-font-family:swiss; mso-font-pitch:variable; mso-font-signature:1627421319 -2147483648 8 0 66047 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:Tahoma; mso-fareast-font-family:"Times New Roman"; mso-bidi-font-family:"Times New Roman"; mso-ansi-language:EN-US;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --&amp;amp;gt; Abstract con borde <!-- /* Font Definitions */ @font-face {font-family:SymbolMT; panose-1:0 0 0 0 0 0 0 0 0 0; mso-font-charset:0; mso-generic-font-family:auto; mso-font-format:other; mso-font-pitch:auto; mso-font-signature:3 0 0 0 1 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:NL; mso-fareast-language:NL;} @page Section1 {size:595.3pt 841.9pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:35.4pt; mso-footer-margin:35.4pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Free radical production is involved in the pathogenesis of Diabetes mellitus. Aim: To study the regulation of NO production by inducible nitric oxide shynthase enzyme (NOS2) in liver of diabetic rat and the role of NO in caspase 8–induced apoptosis. Methodology: Adult male Wistar rats were randomized in 3 groups: (C) control (citrate buffer, pH=4.5), (D) diabetic (streptozotocin (SZ), 60 mg / kg of body weight (bw) ip), (D+I) diabetic with insulin (15 days post-SZ, 30 UI/kg bw, sc, three times a day during 15 days). Rats of three groups were treated with 100 mg/kg bw of aminoguanidine (AG) a day for 10 days. 30 days post-injection of SZ, rats of all groups were autopsied. Results: Glycemia (enzymatic method, g/l): C: 1.17±0.01; D:4.67±0.42*; D+I:0.85±0.01†. Bw (g): C:439±8; D:297±9*; D+I:421±13†. NO in blood (Electronic Paramagnetic Resonance (EPR), arbitrary unit (AU)): C: undetectable; D:22026±2571*; D+I: undetectable†. NO in liver total homogenate (EPR, AU). C: 49305±21384; D:199877±67838*; D+I: 37238±6460†; D+AG: 51493 ±34127†; D+I+AG: 45150±27183†. Western blot, as percentage of C: NOS2 in cytosol: D: 439.7±56.5*; D+I:238.0±66.0†, D+AG:265.3±55.4†; D+I+AG: 126.0±8.6†. Caspase-8 activity (colorimetric method, AU): C:3.8±1.8 D:57.8±2.7*; D+I:2.3±0.9†; D+AG:4.5±3.8†. *p<0.05 vs C. †p<0.05 vs D. C and C+AG showed no differences. Conclusion: Results show that hyperglycemia induces an increase in liver NOS2 with the consequent increase in NO production which activates caspase-8.We suggest that NO is an important mediator in liver diseases like diabetes due to its participation in up-regulation of caspase-8.