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This study aims to scrutinize the efficacy of chitosan (CT) on cardio-lipotoxic responses elicited by a high-fat diet (HF).

Thirty-six male Wistar rats were distributed across six groups (n = 6): normal diet (ND), HF, ND-5%CT, HF-1%CT, HF-3%CT and HF-5%CT, for seven weeks. Blood and cardiac tissues were processed for biochemical, immunohistochemical and histopathological analyses.

Ingestion of HF induced hyperlipidaemia and lipid accumulation, leading to increased body and heart weight by 70.5% (p < 0.0001) and 124% (p = 0.0021), respectively, compared to ND-groups. Cardiac damage markers (creatine kinase, lactate dehydrogenase and malondialdehyde) were higher in the HF-group compared to control rats. Also, atherogenic and coronary risk indices were significantly elevated by 155% (p = 0.0044) and 174% (p = 0.0008), respectively, compared to control rats. Rats fed HF had significantly reduced cardiac antioxidants (superoxide dismutase, catalase and glutathione peroxidase) and elevated expression of NF-κB-p65 and p53 (p < 0.0001) in the cardiac tissues. Histology revealed lipid inclusions in the cardiac tissues of HF-groups. CT (1%–5%) prevented hyperlipidaemia, lipid accumulation, oxidative stress and cardiac damage in HF-fed rats, while greatly improving the histology of the cardiac tissues in HF-fed rats in a dose-dependent manner.

To the best of the authors’ knowledge, this is the first report of the effects of CT against cardio-lipotoxicity elicited by HF diet ingestion. The findings suggest that CT may present a safe therapeutic alternative for managing complications arising from cardio-lipotoxicity.