Description of pathogenesis of paraquat induced mucosal injury
Paraquat, as all bipyridyl salts, is caustic in nature. After ingestion,
the local corrosive effects of paraquat cause erythema, irritation to
the oral and gastrointestinal mucosa; this further worsens to ulceration
and sloughing of the mucosa. The cellular effects of paraquat are
exerted due to redox cycling leading to the formation of reactive oxygen
species, whose concentration increases significantly in time, which can
lead to a situation described as oxidative stress. This phenomenon
occurs when there is an overproduction of reactive oxygen species, the
high overwhelm the natural radical blocking or scavenging mechanisms of
the existing antioxidant defense systems. This intracellular oxidative
stress is generated by accumulation of superoxide anion, hydrogen
peroxide, and hydroxyl radicals within the cells. Destructive actions of
reactive oxygen species on the cells include: free radical-mediated
lipid oxidation leading to production of phospholipid peroxides,
oxidative damage of proteins, carbohydrates and nucleic acids.8 9. The effects eventually lead to
the subsequent disruption of cellular metabolism, apoptosis and finally
programmed cell death. These effects eventually cause epithelial
thinning and mucosal damage. Therefore, this oxidative stress process
also plays a key role in the associated subsequent mucosal (oral and
gastrointestinal) damage caused by paraquat. Another complication that
arises from the over accumulation of reactive oxygen species is
inflammation. This activate transcription factors which results in
upregulation of pro-inflammatory cytokines, cytokines modulators,
adhesion molecules, and stress responders. This amplification causes a
cycle of constant production of cytokines that result in further damage
and ulceration of the mucosa and increases pain and
discomfort.10 14
Another precipitating factor in the extent and severity of oral mucosal
injury is microbial colonization of the ulcers and the damaged mucosa.
The oral cavity is coated by a plethora of bacteria, and some of these
bacteria are harmful and are implicated in oral diseases (caries and
periodontitis) and several systemic diseases.13 Most
ulcers are covered by a whitish pseudomembrane composed of dead cells
and fibrin. The pseudomembrane creates a favorable environment for
bacterial colonization by both Gram-positive and Gram-negative
organisms. Secondary infections caused by the bacteria and by-products
of bacterial metabolism further intensifies mucosal inflammation,
leading to further damage.15 Figure 1