The Toxic Effects of Aflatoxin B1 and Aflatoxin M1 on Kidney through Regulating L-Proline and Downstream Apoptosis

Abstract

The toxic effects and potential mechanisms of aflatoxin B1 (AFB1), aflatoxin M1 (AFM1), and AFB1+AFM1 in the kidney were studied and compared in HEK 293 cells model and CD-1 mice model. The 35-day subacute toxicity mice model was constructed, biochemical indicators and kidney pathological staining were detected, kidney metabonomics detection was performed, and the metabolites were analyzed, and then the related toxicity mechanism was validated. Results showed that AFB1 (0.5 mg/kg), AFM1 (3.5 mg/kg), and AFB1 (0.5 mg/kg)+AFM1 (3.5 mg/kg) activated oxidative stress and caused renal damage. The relative concentration of the metabolite L-proline was found to be lower in aflatoxins treatment groups when compared with the control ( P < 0.05). Moreover, with the treatment of aflatoxins, proline dehydrogenase (PRODH) and proapoptotic factors (Bax, Caspase-3) were upregulated, while the inhibitor of apoptosis Bcl-2 was downregulated, at both the mRNA and the protein levels, comparing with the control ( P < 0.05). In addition, the combined effect of AFB1 and AFM1 was validated, for the toxicity of the combination was stronger than the other two groups. In conclusion, AFB1 and AFM1 caused kidney toxicity by activating oxidative stress through altering expression of PRODH and L-proline levels, which then induced downstream apoptosis.