Development, optimization, and validation of Inflammatory Bowel Disease rat model using isotretinoin

Area of Science:

• Gastroenterology
• Pharmacology
• Toxicology

Background:

• Inflammatory Bowel Disease (IBD) is a complex disorder with unclear etiology.
• Previous studies suggest a link between isotretinoin use and IBD development.
• This research aims to establish a causal relationship and develop a relevant animal model.

Purpose of the Study:

• To investigate the causal relationship between isotretinoin and Inflammatory Bowel Disease (IBD).
• To develop a new animal model for studying isotretinoin-induced IBD.
• To evaluate the dose-dependent effects of isotretinoin on intestinal health.

Main Methods:

• Sprague Dawley rats were divided into five groups: control, indomethacin-induced IBD, and three isotretinoin dose groups (7, 35, 70 mg/kg).
• Animals were monitored for symptomatology, body weight, stool consistency, and frequency.
• Biochemical markers (TBARS, GSH, CAT, SOD, TNF-α), macroscopic, and histological analyses were performed.

Main Results:

• Isotretinoin treatment led to increased mucus in stool and more frequent defecation.
• Significant alterations in oxidative stress markers (TBARS, GSH, CAT, SOD) and elevated TNF-α levels were observed in isotretinoin-treated groups.
• Histological analysis revealed dose-dependent intestinal damage, with the medium dose (35 mg/kg) causing significant crypt abscesses, inflammation, and ulceration.

Conclusions:

• Isotretinoin induces significant damage to the intestinal mucosa, including ulceration, similar to indomethacin-induced IBD.
• Isotretinoin exacerbates IBD conditions in a dose-dependent manner.
• A dose of 35 mg/kg isotretinoin demonstrated the most severe intestinal damage, supporting a causal role in IBD development.