Differences in naphthalene-induced toxicity in the mouse and rat

Area of Science:

• Toxicology
• Pharmacology
• Comparative Pathology

Background:

• Naphthalene causes selective lung damage in mice, primarily affecting Clara cells.
• Species-specific differences in naphthalene toxicity exist between mice and rats.
• Naphthalene depletes non-protein sulfhydryls in mouse tissues more than in rat tissues.

Purpose of the Study:

• To investigate the species-specific toxicity of naphthalene in mice and rats.
• To elucidate the role of naphthalene metabolism in differential organ damage.
• To determine if 1-naphthol mediates naphthalene-induced toxicity.

Main Methods:

• Intraperitoneal administration of naphthalene to mice and rats at varying doses.
• Histological examination of lung and kidney tissues.
• Measurement of non-protein sulfhydryl levels in organs.
• In vitro metabolism studies using lung and liver microsomes.
• Investigation of 1-naphthol's toxicity.

Main Results:

• Mice showed selective lung and kidney damage, while rats did not, even at higher doses.
• Naphthalene significantly depleted non-protein sulfhydryls in mouse lung and kidney compared to rats.
• Mouse lung microsomes exhibited approximately 10-fold greater naphthalene metabolism and covalent binding than rat lung microsomes.
• 1-naphthol did not induce tissue damage or sulfhydryl depletion in either species.

Conclusions:

• Species differences in naphthalene toxicity are linked to differential metabolic activation in lung and kidney tissues.
• Higher metabolic activity in mouse tissues contributes to naphthalene's selective toxicity.
• 1-naphthol is not the primary mediator of naphthalene-induced organ damage.