Gandouling Mitigates CuSO4-Induced Heart Injury in Rats.

Abstract

Simple SummaryWilson’s disease (WD) is a rare autosomal recessive inherited disorder of copper (Cu) metabolism, which is one of the few neurogenetic diseases with a cure. Cu deposition in the heart tissue is a mechanism of cardiac involvement. Importantly, Gandouling (GDL) effectively promotes the excretion of intracellular Cu. Therefore, the purpose of this study was to evaluate the protective effects of GDL on heart injuries and the underlying mechanisms in a copper sulfate (CuSO4)-induced animal model. The results showed that the protective effect of GDL on the heart was superior to that of penicillamine.We assessed the protective effects of Gandouling (GDL) on copper sulfate (CuSO4)-induced heart injuries in Sprague–Dawley rats, which were randomly divided into the control, CuSO4, GDL + CuSO4 and penicillamine + CuSO4 groups. The rats received intragastric GDL (400 mg/kg body weight) once per day for 42 consecutive days after 56 days of CuSO4 exposure, and penicillamine was used as a positive control. The levels of plasma inflammatory cytokines (IMA, hFABP, cTn-I and BNP) were determined using the enzyme-linked immunosorbent assay. The histopathological symptoms were evaluated using hematoxylin and eosin staining and transmission electron microscopy. To determine the underlying mechanism, Western blotting was conducted for the detection of the heme oxygenase 1 (HO-1) expression. The results revealed that GDL supplementation alleviated the histopathological symptoms of the rat heart tissue, promoted Cu excretion to attenuate impairment, and significantly decreased inflammatory cytokine levels in the plasma (p < 0.01). In addition, GDL increased the HO-1 expression in the rat hepatic tissue. The protective effect of GDL on the heart was superior to that of penicillamine. Overall, these findings indicate that GDL alleviates hepatic heart injury after a Cu overaccumulation challenge, and GDL supplements can be beneficial for patients with Wilson’s disease.