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

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. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 345–353, 2014.