Chronic exposure to environmental contaminant nonylphenol exacerbates adenine-induced chronic renal insufficiency: Role of signaling pathways and therapeutic impact of rosuvastatin

Although chronic exposure to environmental contaminants is hazardous to health, the association between chronic kidney disease (CKD) and nonylphenol (NP), a common environmental compound, remains unclear. This study tested the hypothesis that chronic NP exposure aggravated adenine (AD)-induced CKD that could be mitigated with rosuvastatin treatment. Fifty Wistar rats were randomly (n = 10/each group) categorized into normal controls (N _C), NP only (2.0 mg/kg/day), AD only (0.25% AD in fodder), combined NP-AD, and NP-AD with rosuvastatin (20.0 mg/kg/day) (NP-AD-R _OSU). All animals received treatment for 24 weeks prior to being sacrificed. Results showed that ratio of urine protein to creatinine were increased in NP-AD group than in groups N _C, NP, and AD, but reduced in NP-AD-R _OSU group compared with NP-AD group (all p < 0.003). Protein expression of TGF-β and phosphorylated Smad3, indexes of tissue fibrosis, were increased in NP-AD group than in groups N _C, NP and AD, but reduced in NP-AD-R _OSU group compared with NP-AD group (all p < 0.001). BMP-2 and phosphorylated Smad1/5, two indicators of anti-fibrosis, were lower in NP-AD group than in groups N _C, NP and AD, but higher in NP-AD-R _OSU group compared with NP-AD group (all p < 0.001). Protein expressions of JNK and PKC-α in membranous compartment were higher in group NP-AD than in groups N _C, NP and AD, but reduced in NP-AD-R _OSU group compared with NP-AD group (all p < 0.001). More TGF-β + cells but less BMP-2+, CD31+, vWF + and GR + cells were noted in groups AD and NP-AD than in groups N _C, NP and NP-AD-R _OSU (all p < 0.04). In conclusion, NP exposure worsened aggravated AD-induced CKD that could be ameliorated with rosuvastatin treatment.