Galactosamine hepatitis, endotoxemia, and lactulose

Area of Science:

• Hepatology
• Toxicology
• Pharmacology

Background:

• Endotoxins are implicated in galactosamine (Gal-N) hepatitis pathogenesis.
• Lactulose is known to prevent Gal-N-induced hepatic lesions, with an antiendotoxin effect previously postulated.

Purpose of the Study:

• To investigate the protective mechanism of lactulose against Gal-N hepatitis.
• To determine whether the protective effect is due to lactulose itself or its contaminants, specifically galactose.

Main Methods:

• Male Wistar rats were pretreated with commercial lactulose (Duphalac) or purified lactulose.
• Rats were subsequently administered galactosamine (Gal-N).
• Serum enzyme levels (ALT, GDH, SDH) were analyzed 24 hours post-Gal-N administration.

Main Results:

• Commercial lactulose (Duphalac), containing galactose, completely abolished Gal-N toxicity.
• Galactose administered alone at similar concentrations also significantly inhibited Gal-N toxicity.
• Purified lactulose showed diminished protective effects, failing to normalize enzyme levels.

Conclusions:

• The protective effect of commercial lactulose against Gal-N hepatitis is primarily attributed to galactose contamination.
• The previously postulated antiendotoxin effect of lactulose in this model is unlikely.
• Galactose exhibits a competitive inhibitory action against galactosamine toxicity.