What question did this study set out to answer?

This study aims to uncover the hepatic effects of co-exposure to aflatoxin B1 and patulin in mice and HepG2 cells.

April 25, 2026Open Access

Co-Exposure to Aflatoxin B1 and Patulin Induces Hepatic Injury in Mice and HepG2 Cells by Activating Oxidative Stress and Apoptosis

Key Points

This study aims to uncover the hepatic effects of co-exposure to aflatoxin B1 and patulin in mice and HepG2 cells.
C57BL/6 mice and HepG2 cells were assigned to control, aflatoxin B1, patulin, and co-exposure groups.
Hepatic injury was assessed via liver enzyme activity, histopathological alterations, and oxidative stress markers.
Low-cytotoxic concentrations of patulin and NOAELs of aflatoxin B1 were utilized for exposure assessment.
Co-exposure elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) significantly compared to control (p<0.01).
Elevated levels of reactive oxygen species (ROS) and malondialdehyde (MDA) indicative of increased oxidative stress were observed.
Apoptotic response was confirmed by increased Bax, reduced Bcl-2, and activated caspase-3, indicating induced cell death.

Abstract

Aflatoxin B1 (AFB1) and patulin (PAT) are prevalent foodborne mycotoxins with hepatotoxic potential, but the hepatic effects of combined exposure remain largely unclear. This study investigated the hepatotoxic consequences of co-exposure to AFB1 and PAT using no-observed adverse effect levels (NOAELs) in C57BL/6 mice and low-cytotoxic concentrations in HepG2 cells selected by viability screening. Mice and cells were assigned to four groups: control, AFB1, PAT and AFB1 + PAT. Exposure to either toxin individually did not cause evident liver injury, whereas co-exposure significantly elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, reduced liver index, and induced clear histopathological alterations. Co-exposure markedly aggravated oxidative stress, characterized by increased reactive oxygen species (ROS) and malondialdehyde (MDA) and decreased superoxide dismutase (SOD). In parallel, the levels of interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) were elevated, together with the early fibrosis-related markers alpha-smooth muscle actin (α-SMA) and vimentin. The apoptotic response was characterized by increased Bcl-2-associated X protein (Bax) and reduced B-cell lymphoma-2 (Bcl-2), together with cysteine-dependent aspartate-specific protease-3 (caspase-3) activation. These findings indicate that co-exposure to AFB1 and PAT elicits hepatotoxicity through amplified oxidative stress, inflammation, and caspase-dependent apoptosis, supporting the need to further consider mycotoxin co-exposure in toxicological evaluation.

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