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.

The present study was performed to investigate the hepatotoxicity of acetaminophen and the possible hepatoprotective effect of copper(I)-nicotinate in rats through biochemical light and electron microscopy studies. Two groups of rats (39 in total) were used: group I (15 rats) received acetaminophen by intraperitoneal injection in a dose of 1000 mg/kg. While group II (15 rats) received an oral dose of 800 μg/kg copper(I)-nicotinate dissolved in 0.5 mL of saline three times through 24 h and 1 h after the last dose, and 9 rats were kept as control. Blood and tissue samples for biochemical, light, and electron microscop y were collected after 4, 12, and 24 h. Biochemical results showed a significant elevation in ALT, AST, and nitric oxide levels in rats who received acetaminophen only. In contrast, the corresponding levels of treated rats with the copper complex showed a less significant elevation in ALT, AST, and nitric oxide. Light microscopic examination of liver tissue taken from intoxicated animals showed congestion of the vasculature with hydropic and fatty degeneration. Centrilobular necrosis of the hepatocytes with glycogen depletion was observed in the centrilobular areas. Ultrastructural examination showed fatty degeneration, mitochondrial swelling, severe irregular dilatation of RER and SER, loss of glycogen granules, and pyknosis of the nuclei. Examination of livers of animals that received copper complex before intoxication revealed only cup-shaped mitochondria, a mild degree of fatty degeneration, and glycogen depletion with no evidence of necrosis. This work provides evidence for the antioxidant properties of the copper(I)-nicotinate complex and illustrates the pathological changes induced by acetaminophen in liver tissue.

Aflatoxin-contaminated food poses a serious risk to both human and animal health. Copper (1)-nicotinate (Cu +-nicotinate) complex potentiated the prophylactic effect against chronic aflatoxicosis in the experimental animals through the synthesis of less toxic metabolites M1 and Q1 which are easily excreted in urine. To investigate the action of the safety Cu +-nicotinate complex on gene expression of Cytochrome 450 (CYP450) system, the liver tissue samples of orally administered rats for 3 weeks with aflatoxin B1 (AFB1; 30 µg/kg body weight), with and without association of the copper complex (400 µg/kg body weight) were assayed for their gene expression of CYP450 families including 1A2, 3A2 and 2C11 as well as histopathological examination of the hepatic tissue samples was performed. The obtained data denoted that the Cu +-nicotinate complex significantly reduced gene expression of CYP2C11 and CYP3A2 that enhancing the most toxic epoxide metabolite. On the contrary, this complex enhanced the expression of CYP1A2 that synthesize the less toxic metabolite M1 and Q1. The histopathological examination mostly confirmed such observation as the signs of aflatoxicosis were absent in Cu +-nicotinate-treated group. Consequently, it could be predicted that the Cu +-nicotinate complex may be medically used as an inhibitory food additive agent against exposure of aflatoxicosis in the intact animals since the complex contains the copper and nicotinic acid, the two daily required biochemical elements for sustaining live in healthy conditions.