Isoquercitrin Alleviates 5-Fluorouracil-Induced Intestinal Mucositis in Mice by Modulating Inflammation and Oxidative...

Area of Science:

• Pharmacology and Toxicology
• Gastroenterology
• Biochemistry

Background:

• Chemotherapy, particularly 5-fluorouracil (5-FU), often causes severe intestinal mucositis, a debilitating side effect.
• Intestinal mucositis is characterized by inflammation, oxidative stress, and damage to the intestinal lining, significantly impacting patient quality of life.
• Current treatments for chemotherapy-induced mucositis are limited, necessitating the exploration of novel therapeutic agents.

Purpose of the Study:

• To investigate the protective effects of isoquercitrin (ISO) against 5-fluorouracil (5-FU)-induced intestinal mucositis in an animal model.
• To evaluate the impact of ISO on key markers of intestinal damage, inflammation, and oxidative stress.
• To explore the potential mechanisms underlying ISO's therapeutic action, including its interaction with the COX-2 pathway.

Main Methods:

• Animal models were induced with 5-FU and treated with varying doses of ISO (10, 50, 100 mg/kg).
• Histological analysis assessed villus height, crypt depth, mast cell count, and goblet cell depletion in the jejunum.
• Biochemical assays measured malondialdehyde (MDA), myeloperoxidase (MPO), and glutathione (GSH) levels to evaluate oxidative stress and inflammation.
• Immunohistochemistry was used to assess cyclooxygenase-2 (COX-2) expression, particularly in combination with celecoxib (CLX).

Main Results:

• ISO at 100 mg/kg significantly attenuated the reduction in villus height and crypt depth caused by 5-FU.
• ISO treatment reduced mastocytosis and goblet cell depletion in the jejunum.
• ISO-100 demonstrated reduced MDA and MPO levels, alongside increased GSH levels, indicating decreased oxidative stress and inflammation.
• Co-administration of ISO-100 and celecoxib further improved villus height and significantly reduced COX-2 expression induced by 5-FU.

Conclusions:

• Isoquercitrin (ISO) exhibits significant protective effects against 5-fluorouracil-induced intestinal mucositis.
• ISO ameliorates intestinal damage by modulating inflammatory responses and mitigating oxidative stress.
• The findings suggest that ISO, potentially through pathways involving COX-2 inhibition, represents a promising therapeutic candidate for managing chemotherapy-induced gastrointestinal toxicity.