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.

Effect of Dietary Curcumin on Heptorenal Alfla-Toxicosis in Mice

“…The serum creatinine was significantly elevated in AFs group with nonsignificant alteration in relative kidney weight. These results concord with those of (Li et al, 2018). The oxidative stress produced by AFs could alter renal cells membrane leading to leakage of creatinine into the blood that was confirmed by renal tubules degeneration in histopathological sections.…”

“…There are sharp evidence prove that the metabolites of these toxins are excreted in human excreta and biological samples thus it makes it a necessry issue to carefully study these toxins (Jolly et al, 2006). The actual mechanism by which AFs exert their toxicity is still under investigation (Li et al, 2018).…”

Adverse Effects, Transformation and Channeling of Aflatoxins Into Food Raw Materials in Livestock

“…The kidneys are one of the target organs of aflatoxins, and their toxicity is activated by oxidative stress that alters the expression of proline dehydrogenase reducing the proline levels, which induces downstream apoptotic cell death. Moderate focal to diffuse necrosis in the renal tubules and increased renal tubular cells, which may be filled with bile pigments, hyaline, and lipid, with occlusions of their lumens with local edematous changes were reported in the kidneys of aflatoxin-exposed rats (Li et al, 2018). In poultry, the toxic effects exerted by AFB 1 on renal functions included reduced concentrations of calcium, inorganic phosphate, sodium, and potassium and increased levels of urea, creatinine and uric acid (Yilmaz et al, 2018).…”

Black tea and curcumin synergistically mitigate the hepatotoxicity and nephropathic changes induced by chronic exposure to aflatoxin‐B1 in Sprague–Dawley rats

“…Aflatoxin‐B1 (AFB1) is a potent genotoxic and hepatocarcinogenic factor belonging to aflatoxins’ family (Li, Xing, Zhang, Wang, & Zheng, 2018) through developing the AFB1‐8,9‐epoxide (AFBO) of carcinogenicity in liver (Mace et al., 1997). Aflatoxins are produced by Aspergillus flavus and Aspergillus parasiticus in several feedstuffs, that is, nuts, corn, and rice (Li et al., 2018).…”

“…Aflatoxin‐B1 (AFB1) is a potent genotoxic and hepatocarcinogenic factor belonging to aflatoxins’ family (Li, Xing, Zhang, Wang, & Zheng, 2018) through developing the AFB1‐8,9‐epoxide (AFBO) of carcinogenicity in liver (Mace et al., 1997). Aflatoxins are produced by Aspergillus flavus and Aspergillus parasiticus in several feedstuffs, that is, nuts, corn, and rice (Li et al., 2018). Liver is the primary target organ affected by AFB1 causing serious toxicity (Cui et al., 2017; Weng et al., 2017), but other organs are also affected by AFB1‐toxicities (Van Vleet, Watterson, Klein, & Coulombe, 2006), including kidney (Li et al., 2018; Polychronaki et al., 2008), lung (Dvorackova, Stora, & Ayraud, 1981; Kelly, Eaton, Guengerich, Coulombe Jr., 1997; Van Vleet et al., 2006), and alimentary tract (Abdel‐Wahhab, Ibrahim, El‐Nekeety, Hassan, & Mohamed, 2012).…”