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 (NC), 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-ROSU). 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 NC, NP, and AD, but reduced in NP–AD-ROSU 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 NC, NP and AD, but reduced in NP–AD-ROSU 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 NC, NP and AD, but higher in NP–AD-ROSU 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 NC, NP and AD, but reduced in NP–AD-ROSU 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 NC, NP and NP–AD-ROSU (all p < 0.04). In conclusion, NP exposure worsened aggravated AD-induced CKD that could be ameliorated with rosuvastatin treatment.