New insights on the modulatory roles of metformin or alpha-lipoic acid versus their combination in dextran sulfate sodium-induced chronic colitis in rats

作者：Samman Fatma S; Elaidy Samah M^*; Essawy Soha S; Hassan Mohammad S

来源：Pharmacological Reports, 2018, 70(3): 488-496.

DOI：10.1016/j.pharep.2017.11.015

• Alpha-lipoic acid
• Dextran sulfate sodium-induced chronic colitis
• Metformin
• Nuclear factor-kappa-B
• Oxidative stress

Background: Dextran sulfate sodium (DSS)-induced colitis is the most widely used model that resembles ulcerative colitis (UC) in human with challenging chronic mechanistic oxidative stress-inflammatory/ immunological cascades. In models of acute colitis, reduction of oxidative stress and inflammatory burdens beside manipulation of many transcriptional factors were achieved by metformin or alpha-lipoic acid (alpha-LA). Currently, in vivo DSS-induced chronic colitis was conducted and the possible therapeutic roles of metformin and/or alpha-LA were explored.
Methods: Chronic UC was induced by adding 5% DSS orally in drinking water for 7 days followed by 3% DSS in drinking water for 14 days in adult male albino Wistar rats. Intraperitoneal administration of alpha-LA (25 mg/kg, twice/day) and/or metformin (100 mg/kg/day) were set at day 7 of DSS administration and continued for 14 days. Body weights, survival rates, disease activity index (DAI), colonic oxidative stress markers, tumor necrosis factor (TNF)-alpha levels, colonic nuclear factor-kappa-B (NF-kappa B) immunohistochemical expression, and the colonic histopathological changes were observed.
Results: Metformin or/and alpha-LA attenuated the severity of the DSS-induced colitis through improving the reductions in body weights, the DAI, the colonic oxidative stress markers, TNF-alpha, and NF-kappa B levels, and the morphological mucosal damage scores. Significant synergetic therapeutic effects were observed with combined therapeutic regimens.
Conclusion: Therapeutically, metformin and alpha-LA could be administered in chronic colitis. The combination of currently used pharmaceutics with natural and synthetic potent antioxidant compounds will become a therapeutic strategy of choice for UC to improve the quality of life if sufficient clinical trials are available.

• 出版日期2018-6