br Conflicts of interest br Acknowledgments Work in
Conflicts of interest
Acknowledgments Work in the laboratory of SPS is funded by Council of Scientific and Industrial Research (CSIR) Network Project BSC-0111 (INDEPTH) and BSC-0112 (NanoSHE). We are thankful to Director, CSIR-IITR for his constant encouragement and support. We also acknowledge University Grants Commission (UGC), New Delhi for providing research fellowship to AKS. CSIR-IITR communication number for this ApoBrdU DNA Fragmentation Assay Kit manuscript is 3411.
Introduction Nitrobenzene (NB) is a widely used industrial chemical that is used in the production of aniline, pesticides, shoe polishes, analgesics, dyes, and pyroxylin compounds (Li et al., 2003a, Gao et al., 2008). It dissolves slightly in water and will evaporate when exposed to air. In the early 1980s, researchers from Japan and North America had reported the detection of NB in the surface waters (Yamagishi and Miyazaki, 1981, Yurawecz and Purna, 1983). In 2005, the explosion of double-benzene plant in Jilin Province of China caused a major NB water pollution, which making NB toxicology rapidly become the research focus. In China, previous work showed that NB pollution prevailed in the surface water (Kang et al., 2001, Wang et al., 2002, Wang et al., 2003, Tian and Shu, 2003, Li et al., 2006). NB is considered a hazardous air pollutant (HAP), and has proven to be an animal carcinogen. Although the mechanism leading to an NB-induced tumour is still unknown, the intermediates formed by its metabolism, such as nitrosobenzene (NOB) and phenylhydroxylamine (PH), play important roles in the process of NB carcinogenesis (Howard et al., 1983). NB is classified as a Group B2 chemical according to the 1986 cancer guidelines (Us, 1986, Cattley et al., 1994), i.e., a likely human carcinogen (US EPA, 1996). The mechanisms of chemoprevention are diverse, including modulation of a covalent interaction of a carcinogen with DNA, modulation of the DNA repair processes, antioxidation, and modulation of enzyme activities and cell proliferation (Lippman et al., 1994). Recent studies have indicated that the NB toxicity in mammals may be related to an increased production of reactive oxygen species (ROS), leading to oxidative damage (Han et al., 2001). ROS is products of the electron transport chain, enzymes, and redox cycling and their production may be enhanced by xenobiotics (Oruç, 2010). Oxidative stress occurs when ROSs overwhelm the cellular defences and damage proteins, membranes, and DNA (Kelly et al., 1998). In recent years, increasing emphasis has been on the use of biomarkers as a tool for monitoring both the environmental quality and adaptation of organisms (Oruc et al., 2004). The main antioxidative enzymes functioning in the detoxification of ROS in all organisms are superoxide dismutase (SOD; EC188.8.131.52), catalase (CAT; EC184.108.40.206) and glutathione peroxidase (GSH-Px; EC220.127.116.11). The antioxidant defence system has been extensively studied because of the potential to use oxyradical-mediated responses as biochemical biomarkers (Van der Oost et al., 2003). The CYP450 enzymes are a superfamily of hameoproteins that serve as terminal oxidases in the mixed-function oxidase system for metabolising various endogenous substrates and xenobiotics including drugs, toxins and carcinogens (Dong et al., 2009). The CYP450 enzymes play an important role in the detoxification mechanism. The liver is considered as the main organ for CYP450-mediated biotransformation (Tabrez and Ahmad, 2010). Many studies have reported CYP450 levels and CYP450-dependent enzyme activities observed in response to the presence of different pollutants in the aquatic environment has been reported in many studies worldwide (Bard et al., 2002, Moore et al., 2004). NB has become an important pollutant, and many researchers have reported the its toxicity (Cronin et al., 1998, Xu and Jing, 2002, Lu, 2004, Xu and Yang, 2005). The present study focused on the toxicity of NB in birds, which was previously unknown. The purpose of the present study was to investigate the histopathological characteristics, antioxidant responses and CYP450 enzymes in the liver of NB-treated drakes. These results will enable us to further understand the hepatic intoxication and antioxidation mechanisms affected by NB treatment in drakes.