Sneha Bibyan, Ankita Dwivedi, Deepali Jat
Among the multifaceted etiological factors implicated in neurodegeneration, exposure to environmental toxicants represents a significant contributor. Diethyl phthalate (DEP), long regarded as relatively safe, has been increasingly identified in recent studies as a potent inducer of neurodegenerative processes. DEP is a low-molecular-weight phthalic acid ester that is found in various plastic products, cosmetics, and perfumes, and can be ingested, inhaled, or absorbed through dermal contact. It was found that DEP can easily be metabolised into monoethyl phthalate, which possesses equivalent or higher neurotoxic effects in the zebrafish. To mitigate the effects of DEP on the brain, genistein was administered. The compound is a naturally occurring isoflavone phytoestrogen, extracted primarily from soybeans and other beans. Genistein is known as a pleiotropic agent acting as an estrogen receptor agonist and a protein tyrosine kinase inhibitor. Genistein displays a biphasic response (hormetic) pattern, with low doses exerting protective and antioxidant effects against toxicant-induced injury, whereas high doses induce paradoxical effects that may diminish or reverse these protective actions. This study aims to elucidate the toxicological effects of DEP, evaluate the therapeutic potential of genistein to attenuate DEP-induced toxicity, and investigate the paradoxical effects observed at higher genistein doses.