Nano-curcumin prevents cardiac injury, oxidative stress and inflammation, and modulates tlr4/nf-κb and mapk signaling in copper sulfate-intoxicated rats

Sarawi, Wedad S, Alhusaini, Ahlam M, Fadda, Laila M, Alomar, Hatun A, Albaker, Awatif B, Aljrboa, Amjad S, Alotaibi, Areej M, Hasan, Iman H and Mahmoud, Ayman M ORCID: https://orcid.org/0000-0003-0279-6500 (2021) Nano-curcumin prevents cardiac injury, oxidative stress and inflammation, and modulates tlr4/nf-κb and mapk signaling in copper sulfate-intoxicated rats. Antioxidants, 10 (9). 1414. ISSN 2076-3921

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Abstract

Copper (Cu) is essential for a plethora of biological processes; however, its high redox reactivity renders it potentially toxic. This study investigated the protective effect of curcumin (CUR) and nano-CUR (N-CUR) against Cu cardiotoxicity, emphasizing the role of oxidative stress, TLR4/NF-κB and mitogen-activated protein kinase (MAPK) signaling and cell death in rats. Rats received 100 mg/kg copper sulfate (CuSO4), a pesticide used for repelling pests, and were concurrently treated with CUR or N-CUR for 7 days. Cu caused cardiac injury manifested by elevated serum cardiac troponin I (cTnI), creatine kinase (CK)-MB, and lactate dehydrogenase (LDH), as well as histopathological alterations. Cardiac malondialdehyde (MDA), NF-κB p65, TNF-α, and IL-6 were increased, and reduced glutathione (GSH), superoxide dismutase (SOD) and catalase were decreased in Cu-treated rats. CUR and N-CUR prevented cardiac tissue injury, decreased serum cTnI, CK-MB, and LDH, and cardiac MDA, NF-κB p65, TNF-α, and IL-6, and enhanced cellular antioxidants. CUR and N-CUR downregulated TLR4 and AP-1, and decreased the phosphorylation levels of p38 MAPK, JNK, and ERK1/2. In addition, CUR and N-CUR increased cardiac Bcl-2 and BAG-1, decreased Bax and caspase-3, and prevented DNA fragmentation. In conclusion, N-CUR prevents Cu cardiotoxicity by attenuating oxidative injury, inflammatory response, and apoptosis, and modulating TLR4/NF-κB and MAPK signaling. The cardioprotective effect of N-CUR was more potent than the native form.