Repercussões imunológicas e bioquímicas do tratamento de prednisona em ratos Wistar em modelo de obesidade transgeracional

Abstract

Prednisone (PRED), is a drug belonging to the corticosteroid group, play as an immunosuppressive and anti-inflammatory drug. However, its use requires caution and may trigger several adverse effects, especially in obese patients. Knowing this, the objective of this study was to evaluate the interaction between obesity and immunochemical and biochemical markers in Wistar rats treated with prednisone in a transgenerational obesity model. Obesity was induced by subcutaneous administration of Monosodium Glutamate (MSG - 4g/Kg) in female rats (generation F0) on the 2nd, 4th, 6th, 8th and 10th days of life, while in other females (F0-CONT) was administered saline (2% NaCl) following the same protocol. After 90 days, the rats were classified as obese according to the Lee Index >0.300 and then mated to obtain the F1 generation. Male offspring without MSG administration were classified as part of the control group (NOb/SAL), while obese male offspring were separated into two groups: non-obese (NOb/MSG) and obese (Ob/MSG), all n=12, following the Lee Index score. After 90 days of life, rats were exposed to oral prednisone treatment (1.25 mg/kg/day) for 21 days, where the Tolerance Test Glucose (TOTG) was performed on the 1st and 20th days of treatment and body weight measured weekly. On the last day, the relative liver weight, renal mass and blood samples for the leukogram, immunoglobulins and biochemical measurements were verified. As a result, weight gain was observed in rats when treated with prednisone (NOB/SAL in 16.8%, NOb/MSG in 11.2% and Ob/MSG in 9.2%). In addition, there was an increase in leukocyte levels among the three groups prior to treatment, especially lymphocyte elevation (NOb/MSG 6.1 ± 1.3 and Ob/MSG 9.1 ± 2.4) after treatment, a reduction in leukocyte parameters (NOB/SAL 4.1 ± 1.3; NOb/MSG 2.8 ± 1.4 and Ob/MSG 2.6 ± 0.7) was observed, as well as a fall in immunoglobulin G in the Ob/MSG group. There were no differences in relative organ weights, however there was a reduction in triglycerides in the Ob/MSG group (76.9 ± 18.1) compared to NOb/MSG. The activity rates of the enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) showed that the descendant groups of obese mothers increased their values, where ALT (NOb/MSG 64.5 ± 10.8 and Ob/MSG 42.4 ± 7.4) and AST (NOb/MSG 296 ± 50.1 and Ob/MSG 174.6 ± 57.5). Thus, the changes found show obesity as a proinflammatory disease with neutropenia and lymphocytosis. In addition, the use of prednisone in transgenerational obesity evidenced the occurrence of glucose intolerance, hepatotoxicity, IgG drop and weight gain and immunosuppressive effect, suggesting caution in its use under these conditions.