PINK1/Parkin-mediated mitophagy is activated to protect against AFB₁-induced kidney damage in mice

Aflatoxin B₁ (AFB₁) is a toxic food pollutant that has extensive deleterious impacts on the kidney. Oxidative stress represents the primary mechanism of AFB₁ nephrotoxicity and can also cause mitochondrial damage. Damaged mitochondria can trigger apoptosis leading to kidney injury. PINK1/Parkin-mediated mitophagy can alleviate mitochondrial injury to maintain cellular homeostasis, however, its role in AFB₁-induced kidney damage is unknown. To investigate the effect of PINK1/Parkin-mediated mitophagy on kidney impairment triggered by AFB₁, 40 male wild-type (WT) C57BL/6N mice were first assigned to 4 groups and orally exposed to AFB₁ at 0, 0.5, 0.75, and 1 mg/kg body weight (BW) for 28 days. The results revealed that AFB₁ induced kidney damage, oxidative stress, mitochondrial damage, apoptosis and activated PINK1/Parkin-mediated mitophagy with a dose-dependent effect. Then, 20 male WT C57BL/6N mice and 20 male Parkin knockout (Parkin^-/-) C57BL/6N mice were assigned to 4 groups and orally exposed to AFB₁ at 0, 1, 0, and 1 mg/kg BW for 28 days. The results revealed that Parkin^-/- suppressed mitophagy and exacerbated kidney damage, oxidative stress, mitochondrial damage, and apoptosis under AFB₁ exposure. The aforementioned evidences demonstrate that PINK1/Parkin-mediated mitophagy is activated by AFB₁ and protects against kidney damage in mice.