Time-course and molecular mechanism of hepatotoxicity induced by 1,3-dichloro-2-propanol in rats

Lee, In-Chul; Ko, Je‐Won; Lee, Sang‐Min; Kim, Sunghwan; Shin, In‐Sik; Moon, Og-Sung; Yoon, Won-Kee; Kim, Hyoung-Chin; Kim, Jong-Choon

doi:10.1016/j.etap.2015.06.011

Cited by 14 publications

(18 citation statements)

References 21 publications

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“…Twenty-four healthy male rats were assigned randomly to four experimental groups ( n =6): three experimental groups of 1,3-DCP receiving a single oral dose of 27.5, 55, and 110 mg/kg, respectively, and one control group. The 1,3-DCP doses were selected according to previous studies [ 5 17 18 ]. In a preliminary study, three groups of 3 male rats were exposed to 1,3-DCP at doses of 16.5, 50, and 150 mg/kg.…”

Section: Methodsmentioning

confidence: 99%

“…The contents of MDA and GSH, and the activities of catalase, glutathione reductase (GR), and GST were assessed. Oxidative stress markers in liver were determined by the methods of previous studies [ 17 19 20 ]. In brief, a portion of frozen liver was homogenized in a glass-Teflon homogenizer with 50 mmol/L phosphate buffer (pH 7.4) to obtain a 1:9 (w/v) whole homogenate.…”

Section: Methodsmentioning

confidence: 99%

“…Other mechanisms of toxic action include DNA oxidation, mitochondrial membrane potential breakdown, and intracellular calcium and reactive oxygen species (ROS) induction [ 14 15 16 ]. Recently, we have reported timecourse changes in oxidative stress and apoptotic changes in 1,3-DCP-induced hepatotoxicity in rats [ 17 ]. However, the inflammatory effects of 1,3-DCP on liver were not evaluated in our previous study.…”

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confidence: 99%

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Role of mitogen-activated protein kinases and nuclear factor-kappa B in 1,3-dichloro-2-propanol-induced hepatic injury

Lee

et al. 2016

Lab Anim Res

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In this study, the potential hepatotoxicity of 1,3-dichloro-2-propanol and its hepatotoxic mechanisms in rats was investigated. The test chemical was administered orally to male rats at 0, 27.5, 55, and 110 mg/kg body weight. 1,3-Dichloro-2-propanol administration caused acute hepatotoxicity, as evidenced by an increase in serum aminotransferases, total cholesterol, and total bilirubin levels and a decrease in serum glucose concentration in a dose-dependent manner with corresponding histopathological changes in the hepatic tissues. The significant increase in malondialdehyde content and the significant decrease in glutathione content and antioxidant enzyme activities indicated that 1,3-dichloro-2-propanol-induced hepatic damage was mediated through oxidative stress, which caused a dose-dependent increase of hepatocellular apoptotic changes in the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay and immunohistochemical analysis for caspase-3. The phosphorylation of mitogen-activated protein kinases caused by 1,3-dichloro-2-propanol possibly involved in hepatocellular apoptotic changes in rat liver. Furthermore, 1,3-dichloro-2-propanol induced an inflammatory response through activation of nuclear factor-kappa B signaling that coincided with the induction of pro-inflammatory mediators or cytokines in a dose-dependent manner. Taken together, these results demonstrate that hepatotoxicity may be related to oxidative stress-mediated activation of mitogen-activated protein kinases and nuclear factor-kappa B-mediated inflammatory response.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Role of mitogen-activated protein kinases and nuclear factor-kappa B in 1,3-dichloro-2-propanol-induced hepatic injury

Lee

et al. 2016

Lab Anim Res

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“…In order to prove the potential signaling mechanism of cell activation, the phosphorylation levels of p38, JNK and ERK were measured. It is well documented that the MAPK signaling pathway can be induced in response to a diverse range of extracellular stresses including chemicals and cytokines (35,36). Among these stresses, certain studies have reported that NPs can induce MAPK pathway activation, such as ZnO and CuO (37,38).…”

Section: Discussionmentioning

confidence: 99%

Dextran‑coated superparamagnetic iron oxide nanoparticles activate the MAPK pathway in human primary monocyte cells

Miao

Feng

et al. 2018

Mol Med Report

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With the increase in applications of superparamagnetic iron oxide nanoparticles (SPIONs) in biomedicine, it is essential to investigate the bio‑security of these nanoparticles, especially with respect to the human immune system. In the present study, the biological effects of dextran‑coated superparamagnetic iron oxide nanoparticles (Dex‑SPIONs) on human primary monocyte cells were evaluated. The results of the present study demonstrated that Dex‑SPIONs can be identified in phagosomes or freed in the cytoplasm and did not affect cell viability or induce apoptosis. Notably, there were certain bulky vacuoles and a number of pseudopodia from the cell membrane, suggesting potential activation of human monocyte cells. In addition, the expression levels of pro‑inflammatory cytokines interleukin (IL)‑1β and tumor necrosis factor (TNF)‑α were also increased following treatment with Dex‑SPIONs. Simultaneously, the phosphorylation levels of mitogen‑activated protein kinase (MAPK) p38, c‑Jun N‑terminal kinase 1 and extracellular signal regulated kinase were markedly enhanced following nanoparticle exposure and MAPK inhibitors could abate the production of IL‑1β and TNF‑α. The results of the present study demonstrated that Dex‑SPIONs could activate human monocyte cells and that activation of MAPK pathway may be involved in these effects.

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“…3,5 Indeed, studies have gone further to establish its toxicity. 6,7 Although, the occupational toxicity of 1,3-dichloro-2-propanol is not widely reported, there are reports of its moderate toxicity. 3 Indeed, industrial accident led to fatal hepatitis and necrosis in two middle-aged men who cleaned tank with epichlorohydrin and dichloropropanols.…”

Section: Introductionmentioning

confidence: 99%

Caffeic acid abrogates 1,3-dichloro-2-propanol-induced hepatotoxicity by upregulating nuclear erythroid-related factor 2 and downregulating nuclear factor-kappa B

2019

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1,3-dichloro-2-propanol is a food-borne contaminant reported to cause liver injury. In this study, we evaluated the protective influence of caffeic acid on 1,3-dichloro-2-propanol-induced hepatotoxicity in rats. Rats were randomized into five groups (A–E). Rats received distilled water or caffeic acid (10 or 20 mg/kg body weight) for 7 days. In addition, rats were challenged with 1,3-dichloro-2-propanol on day 7. Caffeic acid prevented 1,3-dichloro-2-propanol-mediated alterations in alkaline phosphatase, alanine and aspartate aminotransferases, albumin and total bilirubin in the serum of rats. Furthermore, caffeic acid lowered superoxide ion, hydrogen peroxide and cytochrome P2E1 while increasing the activities of superoxide dismutase, catalase and glutathione S-transferase in the liver of 1,3-dichloro-2-propanol-treated rats. Caffeic acid raised the levels of nuclear erythroid-related factor 2 (Nrf-2), protein kinase A and phosphoinositide 3-kinase. Caffeic acid pretreatment annulled 1,3-dichloro-2-propanol-mediated alterations in the oxidative stress biomarkers; caspase-3, glutathione, malondialdehyde, protein carbonyl and fragmented DNA, in the liver of rats. Contrastingly, caffeic acid lowered 1,3-dichloro-2-propanol-mediated increase in the levels of nuclear factor-kappa B (NF-κB), tumour necrosis factor-α, interleukin-1β (IL-1β) and IL-6. In addition, caffeic acid preserved the morphological features of 1,3-dichloro-2-propanol-treated rats. Results from this study revealed that caffeic acid protects against 1,3-dichloro-2-propanol-induced hepatotoxicity by enhancing the cytoprotective enzymes through Nrf-2 while lowering inflammation through NF-κB.

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Time-course and molecular mechanism of hepatotoxicity induced by 1,3-dichloro-2-propanol in rats

Cited by 14 publications

References 21 publications

Role of mitogen-activated protein kinases and nuclear factor-kappa B in 1,3-dichloro-2-propanol-induced hepatic injury

Role of mitogen-activated protein kinases and nuclear factor-kappa B in 1,3-dichloro-2-propanol-induced hepatic injury

Dextran‑coated superparamagnetic iron oxide nanoparticles activate the MAPK pathway in human primary monocyte cells

Caffeic acid abrogates 1,3-dichloro-2-propanol-induced hepatotoxicity by upregulating nuclear erythroid-related factor 2 and downregulating nuclear factor-kappa B

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