In vitro effect of N-acetylcysteine on hepatocyte injury caused by dichlorodiphenyltrichloroethane and its metabolites

Abstract

<jats:p> The organochlorine pesticide, dichlorodiphenyltrichloroethane (DDT), is still used to combat the spread of malaria in several developing countries despite its accumulation and known hepatotoxic effects that have been demonstrated both in vitro and in vivo. N-Acetylcysteine (NAC) is a recognized hepatoprotective agent that has been reported to reduce hepatotoxicity initiated by many different compounds. The aim of this study was to determine whether NAC could counter in vitro hepatocyte injury induced by DDT or its two major metabolites, dichlorodiphenyldichloroethylene and dichlorodiphenyldichloroethane. HepG2 cell cultures were used to assess the following parameters of toxicity: cellular viability, intracellular levels of reactive oxygen species (ROS), mitochondrial membrane potential and initiation of apoptosis. None of the three test compounds induced ROS generation, yet exposure to any of the three compounds produced mitochondrial hyperpolarization, which was countered by NAC pretreatment. All three test compounds also induced apoptotic cell death, which was inhibited by NAC. Despite NAC counteracting some adverse intracellular changes due to organochlorine exposure, it appeared to aggravate the cytotoxic effects of the organochlorine compounds at low test concentrations. As the same outcome may also occur in vivo, results from the present study raise concern about the use of NAC as treatment for DDT-induced hepatotoxicity. </jats:p>

Identification of In Vivo Metabolites of Dictamnine in Mice Using HPLC-LTQ-Orbitrap Mass Spectrometry

“…Moreover, DIC exhibits potent cytotoxic activity against human cervix, colon, breast, and lung cancer cell lines, and the main mechanism is by inhibiting cell proliferation and promoting cell apoptosis [8, 9]. Recently, Liang et al reported that DIC as an anticancer agent arrests cells in the S phase of the cell cycle and induces human lung adenocarcinoma A549 cell apoptosis via the mitochondria-mediated caspase-independent pathway [10]. Furthermore, novel synthetic and semisynthetic derivatives of DIC, as potential antitumor agents, have gained increasing attention in medicinal research [11].…”

N-acetylcysteine protects hepatocytes from hypoxia-related cell injury

“…N-acetylcysteine (NAC) is a well-known antioxidative agent which protects multiple organs and cells from ischemic and other damage. Hepatoprotective, anti-inflammatory, immunomodulatory and kidneyprotective effects have been demonstrated [20-26]. Due to its chemical structure, it can act as a glutathione (GSH) precursor and substitute [27].…”

Variation in Mitochondria-Derived Transcript Levels Associated With DDT Resistance in the91-RStrain ofDrosophila melanogaster(Diptera: Drosophilidae)

“…Thus, DDT and/or its metabolites have been identified to disrupt oxidative phosphorylation ( Gregg et al 1964 , Byczkowski et al 1973 , Khan and Cutkomp 1982 , Moreno and Madeira 1991 ). In addition, exposure to DDT resulted in an increased H+ concentration in the mitochondrial intermembrane space (hyperpolarization), which led investigators to suggest the voltage-dependent anion channel (VDAC) as a potential candidate causing the hyperpolarization ( van Tonder et al 2014 ). Studies also indicated that DDT could induce cell apoptosis, leading to cytochrome c upregulation that could cause mitochondrial dysfunction, and in turn caspase activation, ultimately leading to apoptosis ( Song et al 2011 , Shi et al 2013 ).…”