Concurrent inflammation as a determinant of susceptibility to toxicity from xenobiotic agents.

Abstract:

:Sensitivity to the toxic effects of xenobiotic agents is influenced by a number of factors. Recent evidence derived from studies using experimental animals suggests that inflammation is one of these factors. For example, induction of inflammation by coexposure to bacterial endotoxin, vitamin A or Corynebacterium parvum increases injury in response to a number of xenobiotic agents that target liver. These agents are diverse in chemical nature and in mechanism of hepatotoxic action. Factors critical to the augmentation of liver injury by inflammation include Kupffer cells, neutrophils, cytokines such as tumor necrosis factor-alpha (TNF-alpha) and lipid mediators such as prostaglandins, but these may vary depending on the xenobiotic agent and the mechanisms by which it alters hepatocellular homeostasis. In addition, the timing of inflammagen exposure can qualitatively alter the toxic response to chemicals. Inflammation-induced increases in susceptibility to toxicity are not limited to liver. Concurrent inflammation also sensitizes animals to the toxic effects of agents that damage the respiratory tract, kidney and lymphoid tissue. It is concluded that inflammation should be considered as a determinant of susceptibility to intoxication by xenobiotic exposure.

journal_name

Toxicology

journal_title

Toxicology

authors

Ganey PE,Roth RA

doi

10.1016/s0300-483x(01)00523-6

keywords:

subject

Has Abstract

pub_date

2001-12-28 00:00:00

pages

195-208

issue

3

eissn

0300-483X

issn

1879-3185

pii

S0300483X01005236

journal_volume

169

pub_type

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