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Nano NiO induced liver toxicity via activating the NF-?B signaling pathway in rats.

ABSTRACT: Studies have demonstrated that nano NiO could induce liver toxicity in rats, but its mechanism remains unclear. This study aimed to explore the role of the NF-?B signaling pathway in rat liver toxicity after nano NiO exposure. Male Wistar rats were exposed to nano NiO (0.015, 0.06 and 0.24 mg per kg b.w.) and micro NiO (0.24 mg per kg b.w.) by intratracheal instillation twice a week for 6 weeks. To investigate the liver toxicity induced by nano NiO, the indicators of liver function and inflammatory response were detected, and the histopathological changes were observed. The levels of NF-?B signaling pathway related gene and protein expression were examined using RT-qPCR and western blot techniques in the liver tissue. The results showed that the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyltranspeptidase (GGT) increased after nano NiO exposure. Cellular edema, hepatic sinus disappearance, and neutrophil and lymphocyte infiltration were observed. Nano NiO increased the concentrations of pro-inflammatory cytokines (IL-1? and IL-6), but decreased the levels of anti-inflammatory cytokines (IL-4 and IL-10). It also induced the upregulation of TNF-?, NF-?B-inducible kinase (NIK), I?B kinase alpha (IKK-?) and NF-?B mRNA, while inducing the downregulation of the inhibitor kappa B (I?B) alpha. In addition, we found that the protein content of NIK, IKK-?, p-IKK-?, p-I?B-? and NF-?B was elevated, whereas that of I?B-? was reduced. The results indicated that the NF-?B signaling pathway played an important role in rat liver toxicity induced by nano NiO.

SUBMITTER: Liu F

PROVIDER: S-EPMC6060624 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Nano NiO induced liver toxicity <i>via</i> activating the NF-κB signaling pathway in rats.

Liu Fangfang F Chang Xuhong X Tian Minmin M Zhu An A Zou Lingyue L Han Aijie A Su Li L Li Sheng S Sun Yingbiao Y

Toxicology research 20170208 2

Studies have demonstrated that nano NiO could induce liver toxicity in rats, but its mechanism remains unclear. This study aimed to explore the role of the NF-κB signaling pathway in rat liver toxicity after nano NiO exposure. Male Wistar rats were exposed to nano NiO (0.015, 0.06 and 0.24 mg per kg b.w.) and micro NiO (0.24 mg per kg b.w.) by intratracheal instillation twice a week for 6 weeks. To investigate the liver toxicity induced by nano NiO, the indicators of liver function and inflammat ...[more]

PMID: 30090495

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Project description:BackgroundCurcumin has been demonstrated to exert anti-oxidant, anti-fibrotic, anti-inflammatory, and anti-cancer activities. This study was conducted to observe the effect and inner mechanism of curcumin in rats with radiation-induced liver damage (RILD).MethodsThirty SD rats were classified into Control, Radiation group and Curcumin (Cur) + Radiation group (n = 10 in each group). The changes in body weight of the rats were observed on the 3rd, 7th and 14th days after the treatment with curcumin. On the 14th day post treatment, the heart blood of the rats was drawn for measurement of liver function indices including total protein (TP), alanine aminotransfetase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) as well as aspartate aminotransfetase (AST). Subsequently, the rats were euthanized and liver tissues were taken to observe liver morphological changes using hematoxylin-eosin (HE), and to analyze apoptosis condition using transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assays. Meanwhile, the oxidative stress level in liver tissue homogenate was determined by biochemical analysis. The expression of nuclear factor kappa B (NF-κB) pathway-associated and apoptosis-associated proteins was detected using Western blot analysis, and the expression levels of inflammatory factors were measured by Enzyme-linked immunosorbent assay (ELISA).ResultsThe reduced body weight was observed in rats of the Radiation group compared to the Control and Cur + Radiation groups on day 14. In the Radiation group, hepatic cell edema and inflammatory cell infiltration could be visible under the light microscope, and the hepatocytes presented with vacuolar degeneration. In the Cur + Radiation group, the hepatocytes swelled under the microscope, but the pathological changes were alleviated in comparison with the Radiation group. RILD rats with curcumin treatment presented with decreased ALT, AST, ALP, LDH, and maleicdialdehyde (MDA) levels, and elevated TP, superoxide dismutase (SOD), caspase activated DNase (CAD) and glutathione (GSH) levels. Apoptosis and inflammation in rats with RILD were up-regulated, and the NF-κB pathway was activated, but they were reversed after continuously intragastric administration of curcumin for 14 days.ConclusionOur study highlights that curcumin treatment reduces the liver damage caused by radiation through the inhibition of the NF-κB pathway.

Project description:Brain damage following cerebral ischemia-reperfusion (I/R) is a complicated pathophysiological course, in which inflammation and oxidative stress have been suggested to serve an important role. Toll-like receptor 4 (TLR4) has been suggested to be involved in secondary inflammatory process in cerebral ischemia. Nuclear factor erythroid 2-related factor 2 (Nrf2), an important regulator of the antioxidant host defense, maintains the cellular redox homeostasis. Tissue kallikrein (TK) has been proven to elicit a variety of biological effects in ischemic stroke through its anti-inflammatory and anti-oxidant properties. However, the mechanisms underlying its beneficial effects remain poorly defined. The present study examined the hypothesis that TK attenuates ischemic cerebral injury via the TLR4/nuclear factor-κB (NF-κB) and Nrf2 signaling pathways. Using a transient rat middle cerebral artery occlusion (MCAO) model, the effects of immediate and delayed TK treatment subsequent to reperfusion were investigated. The neurological deficits, infarct size, and the expression of TLR4/NF-κB and Nrf2 pathway in ischemic brain tissues were measured at 24 following MCAO. The results indicated that TK immediate treatment significantly improved neurological deficits and reduced the infarct size, accompanied by the inhibition of TLR4 and NF-κB levels, and the activation of Nrf2 pathway. Furthermore, TK delayed treatment also exerted neuroprotection against I/R injury. However, the neuroprotective effect of TK immediate treatment was better compared with that of TK delayed treatment. In conclusion, the results indicated that TK protected the brain against ischemic injury in rats after MCAO through its anti-oxidative and anti-inflammatory effects. Suppression of TLR4/NF-κB and activation of the Nrf2 pathway contributed to the neuroprotective effects induced by TK in cerebral ischemia. Therefore, TK may provide an effective intervention with a wider therapeutic window for ischemic stroke.

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Nano NiO induced liver toxicity via activating the NF-?B signaling pathway in rats.

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Nano NiO induced liver toxicity <i>via</i> activating the NF-κB signaling pathway in rats.

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