Lycopene attenuates AFB1-induced renal injury with the activation of the Nrf2 antioxidant signaling pathway in mice

Abstract

Oxidative stress is an important molecular mechanism for kidney injury in aflatoxin B₁ (AFB₁) nephrotoxicity. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master transcription factor for regulating the cellular oxidative stress response, which has been confirmed in animal models. Lycopene (LYC), a natural carotenoid, has received extensive attention due to its antioxidant effect with the activation of Nrf2. However, the role of LYC in protecting against AFB₁-induced renal injury is unknown. To evaluate the chemoprotective effect of LYC on AFB₁-induced renal injury, forty-eight male mice were randomly divided into 4 groups and treated with LYC (5 mg per kg of bodyweight) and/or AFB₁ (0.75 mg per kg of bodyweight) by intragastric administration for 30 days. AFB₁ and LYC were respectively dissolved in olive oil. We found that AFB₁ exposure significantly increased the serum concentrations of blood urea nitrogen (BUN) and serum creatinine (SCR), and caused damage to the renal structure. Notably, LYC potentially alleviated AFB₁-induced kidney lesions through attenuating AFB₁-induced oxidative stress. Renal nuclear factor-erythroid 2-related factor 2 (Nrf2) and its downstream target gene (CAT, NQO1, SOD1, GSS, GCLM and GCLC) translation and protein expression were ameliorated by pretreatment with LYC in AFB₁-exposed mice. These results suggested that LYC potentially alleviates AFB₁-induced renal injury. This effect may be attributed to the enhancement of renal antioxidant capacity with the activation of the Nrf2 antioxidant signaling pathway.