Patulin-induced oxidative DNA damage and p53 modulation in HepG2 cells

Zhou, Simin; Jiang, Liping; Chen, Geng; Cao, Jun; Zhong, Laifu

doi:10.1016/j.toxicon.2009.08.019

Cited by 46 publications

(24 citation statements)

References 36 publications

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“…Most of β cells exhibited convolution of the cell membrane, electron dense cytoplasm, irregular heterochromatic nuclei and few secretory granules. These changes might be due to DNA damage secondary to lipid peroxidation, excess reactive oxygen species and glutathione depletion causing cell cycle arrest [8] . In agreement with this hypothesis previous studies found that lipid peroxides react with Fe2 in the nucleus to generate the alkoxyl radical which attacks DNA (21).…”

Section: Discussionmentioning

confidence: 99%

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Can Goji Berry Extract Attenuate Pancreatic Structural Changes Induced by Patulin Toxin in Male Albino Rats?

Soliman

2017

Egyptian Journal of Histology

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Introduction: Patulin is considered the most common mycotoxins in moldy fruits especially apples and its products like juice and compote. Goji berry (lycium barbarum fruit) is a traditional Chinese herb. It has several biological activities as antioxidant, anti-aging and hypoglycemic properties. Aim: To demonstrate the toxic effect of patulin on the pancreatic tissue and to evaluate the possible role of goji extract. Material and Methods: Forty adult male albino rats were divided equally into four groups. Group I served as the control group. Group II received subcutaneous injection of 2 ml/kg/day goji extract for four weeks. Group III received subcutaneous injection of patulin 0.2 mg/kg/day for four weeks. Group IV received patulin and goji extract with the same previous doses for four weeks. Histological and immunohistochemical studies were done. Results: The administration of patulin led to degenerative changes in the pancreas. There was a significant increase in caspase-3 positive cells in both acini and islets of Langerhans. Ultrastructural examination revealed heterochromatic nuclei, cytoplasmic vacuoles and few secretory granules in acinar cells. The β cells of the islets exhibited a significant decrease in the area percentage and intensity of insulin positive cells. Goji extract could effectively improve these histological changes. Conclusion: Patulin toxicity affected both exocrine acini and β cells of islets of Langerhans. The goji extract had a protective role on this toxicity.

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Section: Discussionmentioning

confidence: 99%

“…Besides, patulin might have diabetogenic effect [7] . Its toxicity is associated with the formation of reactive oxygen species and depletion of cellular glutathione which is a main intracellular antioxidant, and induced oxidative DNA damage and cell death [8] . It was proved that oxidative stress is an apoptosis inducer [9] .…”

Section: Introductionmentioning

confidence: 99%

Can Goji Berry Extract Attenuate Pancreatic Structural Changes Induced by Patulin Toxin in Male Albino Rats?

Soliman

2017

Egyptian Journal of Histology

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“…The high affinity of sulfhydryl binding by PAT and associated oxidative stress due to GSH depletion has been reported in both in vitro and in vivo models (McKinley, Carlton et al 1982, Zhou, Jiang et al 2010. There is limited evidence, however, on the mechanism of activation of the AO response pathways by PAT in kidney cells.…”

Section: Discussionmentioning

confidence: 99%

“…We also found a corresponding increase in ROS levels. An imbalance in intracellular antioxidant and oxidant levels promotes ROS-mediated damage to macromolecules (Zhou, Jiang et al 2010). However, innate cellular mechanisms are effected in an attempt to maintain redox homeostasis.…”

Section: Discussionmentioning

confidence: 99%

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Patulin triggers NRF2-mediated survival mechanisms in kidney cells

Pillay

Phulukdaree

Nagiah

et al. 2015

Toxicon

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Patulin (PAT), a mycotoxin contaminant of apples and apple products, has been implicated in nephrotoxicity. PAT depletes glutathione (GSH) and elevates reactive oxygen species (ROS).The antioxidant (AO) response is activated by Nuclear erythroid 2-related factor (NRF2) and enhanced by Silent information regulator 3 (SIRT3). The effects of PAT on these molecules have yet to be examined. We investigated the effects of PAT on AO response survival pathways in human embryonic kidney cells (HEK293).PAT cytotoxicity on HEK293 cells was evaluated (MTT assay; 24h; [0-100µM]) to determine an IC 50 . GSH levels were measured using luminometry. Intracellular ROS was evaluated by flow cytometry. Protein expression of Keap1, NRF2, SIRT3 and PGC-1α was quantified by western blotting and gene expression of SOD2, CAT and GPx was evaluated by qPCR.PAT caused a dose dependent decrease in HEK293 cell viability and a significant increase in levels of intracellular ROS (p=0.0006). A significant increase in protein expression (p=0.029)

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