RESUMO
BACKGROUND: A spontaneous mutant rat with a hairless phenotype and an intact thymus was discovered in a long-standing Sprague Dawley-National Institute of Nutrition (SD/NIN) rat colony at a national animal resource facility. OBJECTIVE: We conducted extensive phenotypic and biochemical analyses on this mutant strain to determine its suitability as a preclinical model for immunocompetent testing in noncommunicable disease research. MATERIALS AND METHODS: We subjected the mutant rats to strict and frequent phenotypic and genetic surveillance to accomplish this objective. The animals were assessed for food intake, body weight, blood cell profile, clinical chemistry, adipose tissue deposition, and bone mineral density (BMD) using total electrical body conductance (TOBEC) and dual-energy X-ray absorptiometry (DXA) analysis. RESULTS: Initially, only two hairless mutant rats, a male and a female, were born from a single dam in the SD/NIN rat strain. However, the results indicate that the mutant colony propagated from these unique pups displayed distinct phenotypic features and exhibited differences in feeding behavior, weight gain, and clinical biochemistry. The food conversion rate was significantly higher in nude females (2.8-fold) while 26% lower in nude males. Both sexes of nude rats had significantly higher triglycerides and lower glucose levels in females. However, glucose levels did not change in male nude rats. Furthermore, nude female and male rats had significantly lower fat (TOBEC) and bone mineral content (DXA). Nonetheless, BMD was only slightly lower (7%-8%) compared to the heterozygous groups. CONCLUSIONS: These findings indicate that the spontaneous mutant rat has the potential to serve as an immunopotent and modulatory testing system in pharmacokinetics/pharmacodynamics and toxicology, which can be further explored for therapeutic drug discovery.
Assuntos
Doenças não Transmissíveis , Ratos , Masculino , Feminino , Animais , Ratos Sprague-Dawley , Ratos Nus , Densidade Óssea , GlucoseRESUMO
Diabetic retinopathy (DR) is one of the major causes of blindness all over the world. According to the previous studies, impaired glucose tolerance (IGT) has been linked to retinal dysfunction/vascular damage. Decreased retinal function is an initial event of early DR. Although the biochemical and molecular events are not fully understood, glial activation, angiogenesis and oxidative stress are some of the pathways associated with early retinal abnormalities. Since IGT is associated with development of retinal dysfunction/vascular damage; as a preventive strategy, we have studied beneficial effect of Cinnamon as a hypoglycaemic agent on long-term IGT induced retinal abnormalities using neonatal streptozotocin (nSTZ) rat model. Control, IGT rats were maintained on AIN-93M diet alone and another set of IGT rats were maintained on AIN-93M diet with 3% Cinnamon for 8 months. At the end of the study, untreated IGT rats developed retinal functional abnormalities as assessed by electroretinogram (ERG) and the retinal structure did not alter as assessed by H&E staining. Further, increase in expressions of GFAP, VEGF and decreased expression of rhodopsin in untreated IGT rat retinas. 4-HNE, a marker of oxidative stress was also elevated in IGT state. Supplementation of Cinnamon to IGT rats had lowered fasting and postprandial glucose levels and also prevented retinal functional abnormalities. Further, Cinnamon protected photoreceptor cell damage, suppressed glial activation, angiogenesis and oxidative stress as there was an improved rhodopsin expression, inhibited elevated expressions of GFAP, VEGF and 4-HNE respectively. In conclusion, Cinnamon attenuated IGT induced retinal abnormalities probably through its hypoglycemic property.
