Effects of short-term exposure to low doses of bisphenol A on cellular senescence in the adult rat kidney

Abstract

Bisphenol A (BPA) is one of the primary chemicals produced by volume worldwide. Extensive literature has raised many concerns about its possible involvement in the pathogenesis of kidney diseases, but its contribution has not been extensively studied. During cellular senescence, the interference of lipofuscin with cellular functions promotes further senescence, causing cellular malfunction. Insulin-like growth factor-1 (IGF-1) plays an important protective role in the setting of kidney injury. The goal of the present work was to evaluate the effects of short-term treatment with low doses of BPA on cellular senescence in adult rat kidneys. Male Wistar rats were injected with vehicle (CONTROL group) or 50 or 500 μg/kg/day of BPA for 1 week (BPA50 and BPA500 groups, respectively). The kidneys were fixed in 4% buffered formaldehyde and embedded in paraffin. Immunohistochemical analyses were performed, and an immunoreactive score (IRS) was calculated. Lipofuscin autofluorescence was used for the study of cellular senescence. The renal cortex showed diffuse autofluorescent lipofuscin signal in the proximal convoluted tubules (PCTs) of males in the BPA50-treated (weak intensity) and BPA500-treated (strong intensity) groups, but not in CONTROL males. Labeling of cortical PCTs with anti-IGF-1 antibodies showed an IRS of 0 in the CONTROL group, but IRSs of 4 and 6 in the BPA50- and BPA500-treated groups, respectively. The present results suggest that low, “safe” doses of BPA induce renal injury, as measured by histological signs of renal changes, increased cellular senescence, and activation of cellular repair systems in PCTs.

Ratlarda BPA ile Oluşturulan Böbrek Hasarında Ellajik Asit Uygulamasının DNA Hasarı ve Bazı Böbrek Fonksiyon Parametreleri Üzerine Etkisi

“…Bir başka deyişle BPA, kısa süreli ve düşük dozda ya da uzun süreli yüksek dozda olması fark etmeksizin DNA hasarına yol açmaktadır. BPA'ın subkutanöz olarak 50 ve 500 μg/kg/gün dozunda ratlara bir hafta süreyle uygulandığı bir başka çalışmada (40) BPA kullanımının böbrek hasarı biyo-belirteci olarak kabul edildiğini ifade eden bu çalışmada, subkutanöz olarak kullanıldığı durumda bile BPA'nın böbreklerde filtrasyon oranının düşmesine neden olduğu belirtilmiştir. Bu çalışmada BPA'nın sadece oral değil, farklı bir uygulama şekliyle de (subkutanöz) benzer böbrek hasarı oluşturduğu tespit edilmiştir.…”

In focus in HCB

“…Clearly, there remains tremendous ongoing public interest in purchasing BPA-free plasticware since its potential toxic properties were first highlighted in the late 1970s (Vogel 2009). In this light, Nunez et al (2023) have now published a manuscript detailing the effects of short-term exposure to BPA on rat kidney. The kidney is amongst the many organs previously shown to be negatively affected by BPA exposure (Gonzalez-Parra et al 2013), likely due to reabsorption of filtered components occurring in the proximal tubule cells.…”

“…In their current study, Nunez et al (2023) have focused especially on aspects of cellular senescence (the state of cell cycle arrest), which combined with the presence of lipofuscin accumulation can result in cell death. They injected adult rats with two different doses of BPA (low and high) each day for 1 week, followed by processing kidney samples for qualitative and quantitative microscopy analyses.…”