Molecular pathology of cerebral TNF-α, IL-1β, iNOS and Nrf2 in forensic autopsy cases with special regard to deaths due to environmental hazards and intoxication

Forensic Sci Med Pathol. 2017 Dec;13(4):409-416. doi: 10.1007/s12024-017-9896-z. Epub 2017 Aug 3.

Abstract

Deaths involved with environmental hazards and intoxication might present with minimal or nonspecific morphological features, which are insufficient to establish a diagnosis. The present study investigated the postmortem brain mRNA and immunohistochemical expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS) and nuclear factor erythroid-2-related factor-2 (Nrf2) in forensic cases. Relative mRNA quantification using Taqman real-time PCR assay demonstrated higher expression of IL-1β, TNF-α and iNOS, and lower expression of Nrf2 in methamphetamine intoxication and hyperthermia cases, higher expression of iNOS in phenobarbital intoxication cases, and higher expression of Nrf2 in phenobarbital intoxication and hypothermia cases. Immunostaining results showed substantial inter-individual variations in each group, showing no evident differences in distribution or intensity. These findings suggest that different inflammatory and antioxidant responses were involved in deaths from different etiologies, and these markers may be useful for evaluating brain damage and responses.

Keywords: Antioxidant response; Environmental hazards; Forensic molecular pathology; Inducible nitric oxide synthase; Inflammatory response; Interleukin-1β; Intoxication; Nuclear factor erythroid-2-related factor-2; Tumor necrosis factor-α.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Asphyxia / metabolism
  • Biomarkers / metabolism
  • Brain / metabolism*
  • Brain / pathology
  • Cause of Death
  • Female
  • Fever / metabolism
  • Forensic Pathology
  • Humans
  • Hypothermia / metabolism
  • Immunohistochemistry
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism*
  • Male
  • Middle Aged
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism*
  • Poisoning / metabolism
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*
  • Wounds and Injuries / metabolism
  • Young Adult

Substances

  • Biomarkers
  • Interleukin-1beta
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide Synthase Type II