Pro-inflammatory and pro-fibrotic pathways induced by high-fat diet in mice kidney are attenuated by dietary administration of (−)-epicatechin

FISCHERMAN L; LITTERIO MC; OCHOA F; CREMONINI E; ZOTTA E; MASETELLE ESPOSITO M; OTEIZA PI; FRAGA CG; GALLEANO M

Parma

Conferencia; 3rd International Conference on Food Bioactives and Health; 2022

3rd International Conference on Food Bioactives and Health

(−)-Epicatechin (EC) is a flavonoid highly present in the human diet, whichintake seems to provide beneficial effects on health. The development ofchronic kidney disease is frequently associated with weight increase,hypertension and/or insulin-resistance and diabetes. The aim of this work wasto evaluate the protective effect on kidney damage of EC administeredsimultaneously with a high fat (HF) diet. C57BL/6J male mice were divided in 4 groups: control-10% fat (C),control + 20 mg EC/kg body weight (CE), HF diet (60% fat), and HF diet + EC(HFE) for 14 w. At the end of the treatments, animals were euthanized, andblood and kidneys were excised. Kidney slices were prepared for histology and immunohistochemistry(IHC), and tissue fragments were isolated and used for biochemicaldeterminations, and western blot, PCR, and EMSA studies. Animals receiving HFDshowed at 14 w, higher values of body weight, fasting glycemia, triglyceridemia,and total cholesterolemia than C and CE; the simultaneous administration of ECwas associated with a decrease in fasting glycemia and triglyceridemia. Interms of kidney function, serum creatinine levels were 1.7± 0.2, 2.1 ± 0.2, 2.5 ± 0.1* and 1.3 ± 0.2** mg/dL for C, CE, HF and HFErespectively (*different than C and CE, **different than HF, p˂0.05), suggestingan impairment in renal function induced by HF that was partially ameliorated byEC. Kidney fibrosis evaluated histologically, using Masson trichrome staining,showed an increase in collagen staining in the HF group, which was lower in theHFE. These results were in parallel with the levels of TGFβ1 by IHC in kidney: 1.0± 0.3,0.9 ± 0.2, 17.4 ± 1.5* and4.9 ± 0.9** units for C, CE, HF and HFErespectively (*different than C and CE, **different than HF, p˂0.05). Regarding inflammatory markers, IL-6 detection by IHC wassignificantly higher in HF group than in the other groups (2.9±0.6; 3.2± 0.9;51± 4*; 2.1± 0.5 units, for C, CE, HF and HFE, respectively, *p˂0.05).Among the pro-inflammatory pathways studied, NFκ-B did not appear to beinvolved in the process, but AP-1 and NLRP3 inflammasome activation was higher in HF,  and mitigated in the HFE group. In summary,dietary EC can protect kidneys from HFD-induced damage by attenuatingpro-fibrotic and pro-inflammatory pathways in mice. This could be extrapolatedto a role for EC in renal health preservation, particularly in subjects sufferingof the dysmetabolism associated with the consumption of high fat diets.