Inorganic arsenic causes intestinal barrier disruption

Area of Science:

• Environmental toxicology
• Gastroenterology
• Cell biology

Background:

• Inorganic arsenic (As) in food and water poses health risks, particularly gastrointestinal disorders.
• Mechanisms of inorganic As toxicity in the intestine are not well understood.
• As(iii) and As(v) are key toxic inorganic arsenic species.

Purpose of the Study:

• To investigate the mechanisms of inorganic arsenic toxicity in human intestinal epithelial cells.
• To elucidate the effects of As(iii) and As(v) on intestinal cell models.

Main Methods:

• Utilized two human intestinal cell models: NCM460 and Caco-2 cells.
• Assessed the release of pro-inflammatory cytokine IL-8.
• Measured the generation of reactive oxygen and/or nitrogen species (ROS/RNS).
• Examined the expression and localization of tight junction proteins (zonula occludens 1 and claudin 1).
• Evaluated the intestinal barrier function.

Main Results:

• Exposure to As(iii) and As(v) significantly increased IL-8 release (57-1135%) and ROS/RNS generation (130-340%) in both cell lines.
• Arsenic treatments altered the distribution of zonula occludens 1 and reduced claudin 1 expression.
• These molecular changes resulted in a loss of intestinal monolayer barrier function.

Conclusions:

• Inorganic arsenic induces pro-inflammatory and pro-oxidant responses in intestinal epithelial cells.
• Arsenic toxicity affects tight junction integrity, compromising the intestinal barrier.
• These findings highlight the mechanisms underlying arsenic-induced gastrointestinal damage.