Inhibiting of Nrf2 Pathway is Involved in Uranium-Induced Rat Acute Nephrotoxicity

Objective  To assess the relationship between Nrf2 pathway injury and uranium-induced acute nephrotoxicity in rats and related potential mechanism.

Method  Adult male SD rats were randomly divided into four groups with six rats each and intraperitoneally injected with a single dose of uranyl acetate at 2.5, 5, or 10 mg/kg or physiological saline (control group). The 24 h urine samples were collected. After two days, dissected kidneys were tested for kidney function related biochemical parameters and oxidative stress indicators. Pathological changes in kidney samples were observed after HE staining. The protein expressions of nuclear factor E2-related factor (Nrf2), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC) in kidney tissue samples were detected by Western blot.

Result  The uranium exposure induced acute nephrotoxicity in rats with decreasing levels of urea nitrogen and creatinine in urine and increasing levels of urea nitrogen and creatinine in serum, indicating damaged renal tissue structure. The uranium exposure also induced an increasing level of malondialdehyde and a decreasing level of reduced glutathione, and suppressed activities of superoxide dismutase and catalase. The low-dose uranium exposure increased the nuclear Nrf2 level and decreased the cytosolic Nrf2 level. However, in the rats exposed to middle or high dose of uranium, a significant decrease was observed in the Nrf2 protein expression and nuclear translocation, as well as the protein expression of Nrf2-targeting HO-1 and GCLC genes.

Conclusion  Uranium exposure in rats induces oxidative stress injury which may cause acute nephrotoxicity. Nrf2 pathway damage could be involved in uranium-induced acute nephrotoxicity in rats.