Author + information
The present study aimed to define whether sulforaphane (SFN) protects from type 2 diabetic cardiomyopathy (DCM) either via Nrf2, MT or both. Our previous studies have shown that SFN protected from DCM in both T1DM and T2DM mouse models along with up-regulating both Nrf2 and metallothionein (MT).
8 weeks of Nrf2-knockout (KO), MT-KO, and their wild-types (WT, C57BL/6J or 129S1) mice were induced T2DM by feeding a high-fat diet (HFD) for 3 months followed by a small dose of streptozotocin (STZ). Age-matched control mice were fed a normal diet (ND) for the same period. Both T2DM and control mice were treated with or without SFN at 0.5 mg/kg five days a week for 4 months along with continual feeding with either HFD or ND, respectively.
SFN prevented diabetes-increased cardiac oxidative damage, inflammation, fibrosis, and hypertrophy along with stimulating Nrf2 and MT expressions in the WT mice. Both diabetic Nrf2-KO and MT-KO mice exhibited greater cardiac damage than their diabetic WT mice, and SFN did not protect in Nrf2-KO mice, and only partially protected in MT-KO mice, from diabetes-induced cardiac damage. SFN cannot induce MT expression in Nrf2-KO mice, but can stimulate Nrf2 function in MT-KO mice.
The present study demonstrates for the first time that Nrf2 plays the pivotal role in SFN cardiac protection from T2DM. SFN-induced MT expression is Nrf2-dependent and also is a key player in Nrf2-mediated cardiac protection induced by SFN from T2DM.