Abstract
This study aimed to explore protective efficacy of Athelia rolfsii exopolysaccharides (AEPS) to mice kidney against lead-exposed injury with a focus on the role of nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway. Lead accumulation in the kidney induces oxidative stress which causes low antioxidant activity, abnormal pathological changes, and apoptosis. Here, the changes in lead levels in the kidney and whole blood proved that AEPS inhibited lead accumulation. It might be related to AEPS enhancing glutathione (GSH) levels and glutathione-s-transferase (GST) activities, as well as the protein abundances of multidrug resistance-associated protein 1 (MRP1) and multidrug resistance-associated protein 2 (MRP2). Moreover, AEPS increased antioxidant activity by upregulating superoxide dismutase (SOD), catalase (CAT) activities, downregulating malondialdehyde (MDA) levels. It also restored kidney function by decreasing blood urea nitrogen (BUN) and creatinine (CRE) levels in the serum. Histopathologic analysis showed that AEPS alleviated the kidney injury induced by lead, too. AEPS also showed anti-apoptosis effect by downregulating caspase-3 and bax expression and upregulating bcl-2 expression. Importantly, AEPS activated Nrf2 signaling pathway by promoting nuclear translocation of Nrf2. However, all-trans-retinoic acid (ATRA), an Nrf2 inhibitor, reversed the effects on AEPS to activation of Nrf2, enhancement of antioxidant, alleviation of kidney injury, restoration of kidney function, prevention of apoptotic, and facilitation of lead exclusion. In brief, AEPS showed kidney protective effect and facilitated lead-expulsion in an Nrf2-dependent manner.
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