Arzu  YAY

OBJECTIVES /BACKGROUND:
Nonylphenol is an alkylphenol compound that has been widely used in the industry. It has endocrine-disrupting properties. The effect of alkylphenol compounds on development has been the subject of a limited number of studies. Herein, we aimed to examine curcumin's effect against nonylphenol toxicity on brain development.

MATERIAL and METHOD:
For this study, 30 pregnant female Wistar albino rats from the Animal Laboratory of Erciyes University, Faculty of Medicine, were used. The rats were randomly divided into the following 5 groups; the control group, corn oil group (150µl/kg/day), nonylphenol group (50µl/kg/day), curcumin group (100mg/kg/day) and curcumin+nonylphenol group (100mg/kg/day+50 µl/kg/day). After the sacrification, histological and immunohistochemical evaluations were made.

RESULT:
Histopathologically, vascular congestion, increased GFAP, and p-tau immunoreactivity intensity was found in the developing brain of the nonylphenol group. Moreover, co-treatment of nonylphenol administrated with curcumin showed slight pathological alterations with vascular congestion.

DISCUSSION:
Alkylphenol compounds are the member of a variety of synthetic environmental estrogen compounds and are widely present in the environment due to industrial discharge (1). Nonylphenol is a typical alkylphenol compound resulting from the industrial discharge and environmental estrogens, with a detrimental feature. Herein, the administration of nonylphenol resulted in severe toxic events in the offsprings of rats. Huma ns are e xposed t o nonylphenol from contaminated drinking water, food, breast milk, food containers, and personal care products (15). Notably, nonylphenol has been detected in various human samples, such as urine, breast milk, adipose tissue, and fetal cord blood (16). Gestation is a critical period of neurodevelopment, and any damage affecting CNS during this period may severely impair the cognitive function, intelligence, motor, and social function (17). The CNS is vulnerable to environmental pollutants, and the adverse effects of nonylphenol on the central nervous system have become a hotspot of research. Exposure to nonylphenol is hypothesized to impair the CNS and cause cognition, attention, and motor dysfunction (18). Priorly, a step-down avoidance test was examined in rats exposed to maternal nonylphenol, and learning and memory ability impairment was observed (19). Nonylphenol exposure of the fetuses may have been through transplacental absorption. The vulnerability of the brains to nonylphenol neurotoxicity is due to the immature blood-brain barrier. In line with the previous sentence, exposure to nonylphenol during the critical periods of brain development irreversibly harmed offspring rats in adolescence or adulthood (20). In various areas, natural plant products have been in use throughout the past (9). Curcumin is a polyphenolic phytochemical derived from Indian dietary fiber spices. It has been used in the treatment of various diseases due to its wide-ranging pharmacological activities for centuries (10). Strikingly, curcumin has been reported as non-toxic and safe for clinical applications in the conducted researches (21). Curcumin’s pivotal role in the regulation of cell differentiation has been the subject of many studies recently. Curcumin could strongly affect the proliferation and differentiation of the neural progenitor cells and the generation, synaptogenesis, and migration of effective nerves (22). Curcumin studies are increasing to explore curcumin’s various therapeutic features, including analgesic, antioxidant, anti-inflammatory, and antimicrobial activities (23). In this paper, we examined curcumin’s role as a potential exclusive prophylactic antioxidative agent in nonylphenol-induced neurotoxicity in the rat model. The animal model was established by maternal nonylphenol gavage during pregnancy. Histopathologically, there were no morphological changes in the brain of the curcumin given animals. The frontal brain regions appeared normal. No neuronal damage was present. There were no glial cell changes, but vascular congestion presence was found in the NP group. In the nonylphenol-induced group, hyperchromatic cells, neuronal eosinophilia, nuclear pyknosis, and neuronal karyorrhexis were observed. Previous studies have reported similar changes (7). These toxic effects of NP were restrained by curcumin pre- treatment, highlighting the neuroprotective action of curcumin. GFAP’s enhanced expression is used as a biomarker indicating gliosis which occurs due to sensitive and specific indices of toxicant and disease-induced neural damage. GFAP expression may be affected by age, neuronal damage, and sex steroid hormones (24). Tau pathology is a common feature of several neurodegenerative disorders, together known as tauopathies. Phosphorylated tau protein (p-tau), an intracellular, microtubule-associated protein, is highly enriched in axons. Hyperphosphorylation and pathological aggregation of Tau indicate an axonal injury and are a common feature of many neurodegenerative diseases with axonal degeneration (25). Therefore these observations, supporting the hypothesis, provide strong evidence of nonylphenol-induced injury in our study.