PROTECTIVE EFFECT OF THE CELLULAR ANTIOXIDANT SYSTEM ON THE FUNCTIONALITY OF THE IMMUNE SYSTEM IN A MURINE MODEL OF HYPERTHYROIDISM

MACRI DELBONO, R; COSTILLA M.; KLECHA A.; ROMEO H.; CREMASCHI G.; BARREIRO ARCOS M.L.

Buenos Aires

Workshop; Frontiers in Bioscience 3; 2018

Conicet IBIOBA-MPSP

<!-- /* Font Definitions */@font-face{font-family:Arial;panose-1:2 11 6 4 2 2 2 2 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536859905 -1073711037 9 0 511 0;}@font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;}@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-520092929 1073786111 9 0 415 0;} /* Style Definitions */p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin-top:0cm;margin-right:0cm;margin-bottom:8.0pt;margin-left:0cm;line-height:107%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:Calibri;mso-fareast-font-family:Calibri;mso-bidi-font-family:"Times New Roman";mso-ansi-language:EN-US;mso-fareast-language:EN-US;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-size:10.0pt;mso-ansi-font-size:10.0pt;mso-bidi-font-size:10.0pt;font-family:Calibri;mso-ascii-font-family:Calibri;mso-fareast-font-family:Calibri;mso-hansi-font-family:Calibri;}@page WordSection1{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.WordSection1{page:WordSection1;}-->BACKGROUND: Hyperthyroidism is characterized by excessive secretion oftriiodothyronine and thyroxine by the thyroid gland. Thyroid hormones (THs) exert actions on growth, metabolism and cellulardifferentiation. OBJECTIVE: To studythe effects of hyperthyroidism on oxidative parameters in murine lymphocyticcells, analyzing their effects on lymphocyte functionality. METHODS: BALB/cmice were treated with T4 (12 mg/l) indrinking water for 30 days or with placebo. Serum hormone levels werequantified by RIA. Reactive oxygen species(ROS) and apoptosis were evaluated by flow cytometry using DCFH-DA andAnnexin-V/PI. The expression of antioxidant enzymes and iNOS were analyzed byqPCR and western blot. Enzymatic activity was quantified by spectrophotometry. Nitrite production and lipoperoxidation levels were evaluatedby the Griess technique and by the TBARs method. RESULTS: Hyperthyroid animalsshowed a greater increase in body weight, compatible with higher feed intake,exhibited irritability and anxiety and had dry and brittle hair. Lymphocytesfrom lymph node (LN) and spleen (S) of hyperthyroid animals showed increased levels of ROS (29.1±2.6% in LNand 26.2±2.1% in S, p<0.005) that was correlated with the increase in theactivity and expression of Catalase and Glutathione Peroxidase-1. Hyperthyroidanimals showed higher iNOS protein expression (37.2±3.0%, p<0.01) and nitrite production(23.1±2.0%, p<0.005).Lymphocytes of the hyperthyroid animals showed higher levels of lipoperoxidation,however, we did not find fragmented nuclei or compaction of their DNA and thelevels of apoptosis were like the controls. Thelymphoid organs showed hyperplasia with an increase in the number of lymphoidcells and a greater proliferative response. CONCLUSIONS: Hyperthyroidism increased cellular metabolism, the production of ROSand NO, involved in the formation of peroxynitrites. The increase in theexpression of antioxidant enzymes protects lymphoid cells from oxidative damageand apoptosis. The increase of NO in controlled amounts could be contributingto a greater immune response