Potential roles of oxidative stress and insulin resistance in diisononyl phthalate induced dyslipidemia and hepatosteatosis in BALB/c mice

Abstract

Exposure to plastic-derived endocrine disrupting chemicals (EDCs) such as phthalates have become a source of concern to human health. Phthalates are applied industrially as plasticizers in the production of various plastic products. They have been reported for the various forms of toxic responses in both human and animal studies. Diisononyl phthalate (DiNP) was recently used to replace di(2-ethylhexyl) phthalate (DEHP) due to some toxicity concerns. However, recent evidences suggest that DiNP may disrupt the endocrine system, alter lipid metabolism and induce hepatic steatosis. Hence, this work was designed to probe the potential impacts of DiNP on oxidative stress biomarkers and insulin resistance as a possible link to dyslipidemia and development of hepatic steatosis. To achieve these, twenty seven (27) male BALB/c mice were distributed into three (3) experimental groups of nine (9) mice each. Group I was the control while mice in groups II and III were exposed to 20 and 200 mg/kg body weight, (bw) DiNP respectively orally (per os, p.o.) for 28 days. Thereafter, plasma insulin, glucose, plasma lipid levels as well as insulin resistance (IR) index were determined. The effects of DiNP on hepatic biomarker of inflammation (tumor necrosis factor alpha, TNF-α), oxidative stress (malondialdehyde, MDA), antioxidants (glutathione peroxidase, reduced glutathione and catalase) were also investigated in addition to liver histopathology. Data obtained show that DiNP especially at 200 mg/kg bw significantly (p < 0.05) alter plasma glucose and lipid profile and induced IR. Other responses observed at this dose level include significant inflammation, oxidative stress and hepatic fatty degeneration (as shown in hematoxylin and eosin stained liver sections). Current findings suggest that insulin resistance and oxidative stress may influence DiNP-induced dyslipidemia and hepatic steatosis in mice.