Effect of Methyl Gallate on 1-Nitropyrene-Induced Keratinocyte Toxicity in a Human and Canine Skin Model

J Microbiol Biotechnol. 2022 Jul 28;32(7):869-876. doi: 10.4014/jmb.2206.06004. Epub 2022 Jun 30.


The skin, which is the largest organ of the human body, is in direct contact with pollutants in the surrounding atmosphere. Meanwhile, 1-nitropyrene (1-NP), the most abundant nitro-polycyclic aromatic hydrocarbon found in particulate matter, is known to have carcinogenic effects; however, studies on its toxicity in human and canine skin are still needed. In this study, we investigated 1-NP-induced apoptosis and inflammatory pathways in HaCaT cells. In addition, we also measured the cytoprotective effect of methyl gallate (MG), which is widely distributed in medicinal and edible plants and is well known for its anti-inflammatory and antioxidant properties. MG inhibited 1-NP-induced cell death and apoptosis pathways, including the cleavage of PARP and activation of caspase-3, -7, and -9. MG also suppressed 1-NP-induced COX-2 expression and phosphorylation of mitogen-activated protein kinases (MAPKs) and MAPK kinases (MAPKKs). Our findings suggest that 1-NP induces skin toxicity in human and canine through apoptosis and inflammatory responses, and moreover, that this can be prevented by treatment with MG.

Keywords: 1-nitropyrene; Apoptosis; HaCaT cells; canine skin; methyl gallate; skin toxicity.

MeSH terms

  • Animals
  • Apoptosis
  • Dogs
  • Gallic Acid / analogs & derivatives
  • Humans
  • Keratinocytes*
  • Mitogen-Activated Protein Kinases / metabolism
  • Pyrenes* / toxicity


  • Pyrenes
  • methyl gallate
  • Gallic Acid
  • Mitogen-Activated Protein Kinases
  • 1-nitropyrene