Mitigating potential ofGinkgo bilobaextract and melatonin against hepatic and nephrotoxicity induced by Bisphenol A in male rats

Abstract

Bisphenol A is one of the anthropogenic chemicals produced worldwide, currently released into the environment and causes endocrine-disruption. The largest environmental compartments of BPA are abiotic associated with water and suspended solids that becomes an integrated part of the food chain. The present study aimed to examine the possible protective role of Ginkgo biloba extract (GBE), melatonin and their combination against BPA-induced liver and kidney toxicity of male rats. Fifty rats were divided into five equal groups: control, BPA, BPA plus GBE, BPA plus melatonin and BPA plus GBE plus melatonin. The elevated activities of plasma ALT and AST in addition to increased levels of urea and creatinine concomitant with the decreased total plasma protein could reflect the injurious effect of BPA. Liver and kidney levels of TBARS were significantly increased, while GSH, SOD and GPX were decreased in BPA-treated rats. Also, CAT and GST activities were significantly disrupted in the liver and kidney of rats treated with BPA. Moreover, BPA significantly increased the proinflammatory cytokine TNF-a in the liver and kidney tissues. The histopathological analysis confirmed these results. All the previous alterations in the liver and kidney could be ameliorated when BPA-treated rats were co-administrated either with GBE, melatonin or their combination. These natural substances could exhibit protective effects against BPAinduced hepato-and nephrotoxicity owing to their antioxidative and anti-inflammatory potentials.

Bisphenol A co-exposure effects: a key factor in understanding BPA’s complex mechanism and health outcomes

“…In vivo melatonin co-exposure with BPA also reduced BPA-induced hepatotoxicity and nephrotoxicity in male rats. Similar effects were also observed with GBE co-exposure in male rats (Wahby et al 2017). GBE is one of the most widely used herbal supplements in Chinese traditional medicine having immunomodulation, antioxidant, anti-inflammatory and anti-tumor activities (Yan et al 2015).…”

“…Naturally occurring compounds or dietary supplements are known to be beneficial in overcoming the deleterious effects of estrogenic EDCs such as BPA on different endpoints such as oxidative stress biomarkers, sex hormone levels, organ morphology, DNA damage and epigenetic modification. These changes may alter the adult phenotype or impact offspring, and even contribute to organ toxicity and carcinogenesis (Dolinoy et al 2007;Wu HJ et al 2013;Wahby et al 2017;Saadeldin et al 2018). However, there can be deleterious effects with some dietary supplements, including increased aneuploidy, endocrine dysfunction, and wide spread changes in epigenetic modifications and gene expression changes (Branco and Lemos 2014;Ribeiro-Varandas et al 2014;Leung et al 2017;Sèdes et al 2018).…”

“…Renal toxicity was also reduced during co-exposure of GBE or melatonin with BPA though a reduction in urea and creatinine levels and a reduction in renal TBARs. Increasing GSH levels and activities of SOD, glutathione Stransferase (GST) and catalase (CAT) were also observed for both GBE and melatonin (Wahby et al 2017).…”

“…Melatonin is an important endogenous hormone that regulates circadian rhythm; and studies have shown that BPA co-exposure with melatonin significantly reduces BPA-induced cell proliferation and BPA-induced oxidative stress (Wu HJ et al 2013;Wahby et al 2017;Wang T et al 2018). Breast cancer cell lines co-exposed with BPA and melatonin showed inhibition of BPA-elevated levels of steroid receptor activators and estrogen response element (ERE) activity and downregulation of phosphorylated extracellular-regulated kinase (ERK) and serine/threonine-specific protein kinase (AKT) (Wang T et al 2018).…”

Can Antioxidants Reduce the Toxicity of Bisphenol?

“…Protective effects against BPA-induced hepato- and nephrotoxicity were observed when the BPA-treated rats were concurrently administered G. biloba extract, melatonin, or a combination thereof. Both the G. biloba extract and melatonin increased the level of GSH and the activity of SOD, GST, and CAT [ 132 , 135 ].…”