RESUMO
BACKGROUND: Chronic kidney disease and inflammation promote loss of Klotho expression. Given the well-established anti-inflammatory effects of omega-3 fatty acids, we aimed to investigate the effect of fish oil supplementation in a model of CKD. METHODS: Male C57BL/6 mice received supplementation with an adenine-enriched diet (AD, n = 5) or standard diet (CTL, n = 5) for 10 days. Two other experimental groups were kept under the adenine diet for 10 days. Following adenine withdrawal on the 11th day, the animals returned to a standard diet supplemented with fish oil (Post AD-Fish oil, n = 9) or not (Post AD-CTL, n = 9) for an additional period of 7 days. RESULTS: Adenine mice exhibited significantly higher mean serum urea, creatinine, and renal expression of the pro-inflammatory markers Interleukin-6 (IL-6), C-X-C motif chemokine 10 (CXCL10), and Interleukin-1ß (IL-1ß), in addition to prominent renal fibrosis and reduced renal Klotho gene expression compared to the control. Post AD-Fish oil animals demonstrated a significant reduction of IL-6, C-X-C motif chemokine 9 (CXCL9), and IL-1ß compared to Post AD-CTL animals. However, serum creatinine, renal fibrosis, and Klotho were not significantly different in the fish oil-treated group. Furthermore, renal histomorphological changes such as tubular dilatation and interstitial infiltration persisted despite treatment. CONCLUSIONS: Fish oil supplementation reduced renal pro-inflammatory markers but was not able to restore renal function nor Klotho expression in an adenine-induced CKD model.
Assuntos
Adenina , Suplementos Nutricionais , Óleos de Peixe/administração & dosagem , Mediadores da Inflamação/metabolismo , Rim/metabolismo , Proteínas de Membrana/metabolismo , Nefrite/dietoterapia , Insuficiência Renal Crônica/dietoterapia , Ração Animal , Animais , Biomarcadores/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Fibrose , Rim/patologia , Rim/fisiopatologia , Proteínas Klotho , Masculino , Camundongos Endogâmicos C57BL , Nefrite/induzido quimicamente , Nefrite/metabolismo , Nefrite/fisiopatologia , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/fisiopatologiaAssuntos
Apoio Nutricional , Distúrbios Nutricionais , Anemias Nutricionais , Doenças Ósseas Metabólicas , Obesidade , Imagem Corporal , Anorexia Nervosa , Bulimia , Hipertensão/dietoterapia , Diabetes Mellitus/dietoterapia , Insuficiência Renal/dietoterapia , Nefrite/dietoterapia , Gastropatias/dietoterapia , Interações Medicamentosas , Comportamento AlimentarRESUMO
Three experimental protocols were carried out with the aim of evaluating the role of protein restriction on the progression of the established adriamycin-induced nephropathy, and whether the protective effect of the diet persists after the diet is discontinued. The effect of a low protein diet (LPD) was studied for 6 weeks in protocol 1, 16 weeks in protocol 2 and for 28 weeks in protocol 3. In protocol 3, one group (LL) received LPD and another (NN) was given a normal protein diet (NPD). A third group (LN) received LPD for 16 weeks and then NPD for 12 weeks and a fourth group (NL) was fed NPD for 16 weeks and then LPD for 12 weeks. In protocol 1 the tubulo-interstitial index (TILI) of rats on LPD (Md = 2, P25 = 0.0; P75 = 3.5) after six weeks, was smaller than that of the animals on NPD (Md = 6.0; P25 = 3.0; P75 = 8.0; p < 0.05). In protocol 2, the group taking LPD presented an area of interstitial fibrosis (IF) (Md = 0.5%, P25 0.2%; P75 = 1.9%) smaller than that of the NPD group (Md = 6.8%; P25 = 5.2%; P75 = 7.1%; p < 0.05). No significant difference in the area of glomerulosclerosis (GSA) was observed between the animals on LPD (Md = 0.0%; P25 = 0.0%, P75 = 0.0%) and NPD (Md = 0.37%; P25 = 02%, P75 = 1.25%; p > 0.05). In protocol 3, the group LL showed GSA (Md = 1.3%; P25 0.6%, P75 = 2.5%) and IF (Md = 3.6%; P25 = 1.6%; P75 = 5.9%) smaller that those of LN (GSA Md = 10.1%; P25 = 6.6%; P75 = 14.8%; IF: Md = 17.3%; P25 = 14.1%; P75 = 24.5%), NL (GSA: Md = 9.1%; P25 = 5.8%; P75 = 11.7%; IF: Md = 25.0%; P25 = 20.4%; P75 = 30%), and NN (GSA: Md = 6.75%; P25 = 4.9%; P75 = 11.7%; IF: Md = 20.9%; P25 = 16.2%; P75 = 32.4%). In conclusion, in order to be effective, LPD must be introduced early and maintained for a long period of tune.