Induction of oxidative stress and histological changes in liver by subacute doses of butyl cyclohexyl phthalate

Abstract

Phthalates are esters of phthalic acid and are mainly used as plasticizers in a wide variety of products and applications. There is no information on butyl cyclohexyl phthalate (BCP) toxicity. This study was performed to evaluate the histopathological effects and to determine oxidative stress inducing potential in liver by subacute exposure of BCP. The animals of the treatment groups were orally administered 100, 200, and 400 mg/kg/day BCP for 5 consecutive days per week during 28 days. As a result, no significant changes were observed in body weight gains, and absolute and relative liver weights of liver of BCP treated mice, when compared with control group. Although the degree of lipid peroxidation in the liver tissue of all BCP exposure groups were significantly higher than those of the control (p < 0.01), SOD and CAT activities in liver tissue of mice of 200 and 400 mg/kg exposure groups were significantly lower than those of the controls (p < 0.01). Moreover, BCP caused dose-dependent histological changes in the liver of mice such as congestions in vena centralis, an enlargement of the sinusoids, degeneration in hepatocytes, vacuole formations and presence of lipid droplets in hepatocytes, eosinophilic cytoplasm. While iNOS immunoreactivity was increased in all treatment groups, Type IV collagen and Connexin 43 immunoreactivities were decreased in all treatment groups compared with the control group. Significant decrease was observed in the number of TUNEL-positive liver cells of BCP treated mice. These results suggested that BCP exposure induces oxidative stress in liver and exposure of BCP during long time period could lead to hepatocarcinogenesis.

Cytotoxicity and genotoxicity of butyl cyclohexyl phthalate

“…Comet assay results of this study clearly showed that the number of damaged nuclei increased resulting in many fold increase in the damage index on exposure with BCP. Our other study results supported that 28 days BCP exposure induces oxidative stress in mice and constitutes an imbalance between scavenging and forming of ROS (Karabay Yavasoglu et al 2014). In the study, we showed that BCP is capable of inducing marked hazardous alteration by the imbalance of the pro/ antioxidant system and the histopathology of liver, in addition to the lipid peroxidation which may be one of the molecular mechanisms involved in BCP-induced oxidative stress in mice.…”

Mitochondrial Involvement in the Adaptive Response to Chronic Exposure to Environmental Pollutants and High-Fat Feeding in a Rat Liver and Testis

“…U nder a stress condition, cells activate compensatory mechanisms that include the modulation of gene expression. In particular, phthalates can induce hepatic toxicity through PPARs transactivation, causing uncontrolled proliferation and hepatic tumorigenesis development [102] . In addition, PPARs have been shown to be directly involved in the regulation of cellular toxicity induced by air, water, and food pollutants [103].…”

Assessment of exposure to Di (2-ethylhexyl) phthalate (DEHP) metabolites and Bisphenol A (BPA) and its importance for the prevention of cardiometabolic diseases

“…Recent studies have shown that DEHP is able to interfere with the insulin signal by reducing the molecules involved in its signal transduction such as IRS1 and Akt and with hepatic glucose uptake and transcriptional regulation of GLUT2 suggesting DEHP exposure impairs insulin signal transduction and alters glucoregulatory events leading to the development of type 2 diabetes in F1 male offspring [57,58]. Phthalates and DEHP cause toxicity in many organs: for example, in liver they alter enzyme activities or gene expression and induce oxidative stress [59,60], induce hepatomegaly and hepatocarcinogenesis [61]; in brain PPARγ hyperactivation leads to apoptosis in undifferentiated neurons [62]. Thus, total daily intake (TDI) for DEHP has been set to 50 μg per kilogram body weight per day (EFSA 2005) while EPA has set the Reference Dose (RfD) to 20 μg per kilogram body weight per day (mg/kg/d) based on increased relative liver weights in guinea pigs [63].…”