Protective effect of copper II ‐albumin complex against aflatoxin B1 ‐ induced hepatocellular toxicity: The impact of Nrf2, PPAR ‐γ, and NF‐kB in these protective effects

Abstract

Copper II-Albumin complex (Cu-II-Albumin complex) is a novel therapeutic target that has been used as anti-inflammatory, antioxidant, and anti-gastrointestinal toxicity. In this study, 40 rats were divided into four groups, normal control (NC), aflatoxicosed group (AF) that received Aflatoxin B1 (AFB1) (50 μg/kg of the AFB1 daily for 3 weeks), AFB1-Cu-II-Albumin prophylactic group (AF/CUC-P) that subjected to intermittent treatment between AFB1 and Cu-II-Albumin complex (0.05 g/kg Cu-II-Albumin complex) day after day for 3 weeks and AFB1-Cu-II-albumin treatment group (AF/CUC-T) that received AFB1 for 3 weeks and Cu-II-albumin complex for another 3 weeks.The hepatocellular protective effect of the Cu-II-albumin complex was assessed by evaluating the liver functions markers, hepatic histopathology, reactive oxygen species (ROS) levels (Nitric Oxide (NO) and malondialdehyde (MDA)), apoptotic genes (caspase-3 and tumor necrosis factor receptor 1 [TNF-R1]) expressions, and serological and molecular biomarkers of hepatocellular carcinoma (histamine and Glucose-Regulated Protein 78 [GRP78], respectively). Our finding showed that Cu-II-Albumin Complex administration had restored liver function, oxidative stress levels, enhanced liver tissue recovery, and reduced the expression of the apoptotic genes of the aflatoxicosed rats. In conclusion, the current study results demonstrated the protective effect of Cu-II-albumin complex against AFB1-induced hepatocellular toxicity. Practical applicationsThe protective effect of Cu-II-Albumin Complex against AFB1-induced hepatocellular toxicity by assessing oxidative stress, liver biomarkers, inflammation, and histological changes of liver tissues. The protective mechanism of the Cu-II-albumin complex was also investigated. More clinical studies are required to evaluate the potential of using the Cu-II-albumin complex as a therapeutic agent against hepatocellular toxicity.

Resveratrol regulates inflammation and improves oxidative stress via Nrf2 signaling pathway: Therapeutic and biotechnological prospects

“…Real‐time quantitative PCR detected mRNA transcripts of Nrf2 pathway (Nrf2, Keap1, NQO1, HO‐1, SOD2 and HSP70). MAC‐T cells' apoptosis and ROS production were both reduced, as was the level of mitochondrial membrane potential (MMP), suggesting that resveratrol can counteract the cytotoxicity generated by aflatoxin B1 in MAC‐T cells (Abo‐Hiemad et al, 2022; Cui et al, 2022; Iqbal et al, 2015; Zhou et al, 2019).…”

Gentiopicroside ameliorates CCl4-induced liver injury in mice by regulating the PPAR-γ/Nrf2 and NF-κB/IκB signaling pathways

“… 19 , 20 PPAR-γ binds to a specific binding site, namely a peroxisome proliferative response element, to promote Nrf2 gene expression, and it possesses antioxidant properties. 21 Nrf2 can regulate the oxidative defense system, and it is primarily involved in the synthesis of reducing factors and the promotion of superoxide decomposition. 21 Anti-oxidative strategies targeting the PPAR-γ/Nrf2 pathway have produced promising results in alleviating liver injury.…”

“… 21 Nrf2 can regulate the oxidative defense system, and it is primarily involved in the synthesis of reducing factors and the promotion of superoxide decomposition. 21 Anti-oxidative strategies targeting the PPAR-γ/Nrf2 pathway have produced promising results in alleviating liver injury. 7 , 8 , 23 In this study, PPAR-γ and Nrf2 expression in the livers of CCl 4 -treated mice was significantly decreased.…”

Copper(II) Complexes with Carnosine Conjugates of Hyaluronic Acids at Different Dipeptide Loading Percentages Behave as Multiple SOD Mimics and Stimulate Nrf2 Translocation and Antioxidant Response in In Vitro Inflammatory Model

“…Furthermore, many reports have highlighted the ability of both Car [ 86 , 87 , 88 ] and Hy [ 89 , 90 , 91 ] to tune Nrf2 in different pathological conditions. Furthermore, several findings have shown a bidirectional interaction between copper and Nrf2 [ 92 , 93 ], the different effects of which have been attributed to copper concentration, cell type, disease pattern, and exposure to drugs or natural compounds [ 94 , 95 , 96 , 97 , 98 , 99 , 100 ]. Thus, we extended our work to ascertain the ability of HyCar to interact with the submicromolar copper present in the culture media and stimulate Nrf2 activity in human fetal osteoblastic cell line (hFOB) treated with the H 2 O 2 -conditioned medium of macrophages [ 101 , 102 ].…”