Protective effect of p53 knockout on 4-nonylphenol-induced nephrotoxicity in medaka (Oryzias latipes)

In the past few decades, environmental pollutants have become common because of misused nonionic surfactants and detergents. Nonylphenol ethoxylates (NPs) are one of the most important contaminants of water. Therefore, the present study aimed to investigate the protective blocking effect of apoptosis (deficient P53 gene) on 4-nonylphenol (4-NP)-induced nephrotoxicity of medaka (Oryzias latipes). We divided 36 fish into six groups: two different control groups of wild type (Wt; Hd-rR) control and p53 (-/-) control, and four different treated with 4-nonylphenol (50 μg/L and 100 μg/L) for 15 days. Histology, immunochemistry, and TUNEL assays confirmed that 4-NP causes nephrotoxicity. Our results showed that 4-NP administration significantly disturbed the kidney structure and function and 4-NP-treated fish showed dilated glomerular vessels, had less glomerular cellular content, decreased expression of glomerular proteins, and an increased level of apoptosis compared with a Wt control group (P < 0.05). As p53 is an apoptotic inducer, some protection in p53-deficient medaka was found as nephrotoxic effects of 4-NP were minimized significantly. Our study demonstrated for the first time to our knowledge that 4-NP induces apoptosis, causing nephrotoxicity in medaka. We found that blocking apoptosis blocking was able to protect the kidney from the toxic effects of 4-NP.