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Anti-Inflammatory Activity of Chitosan and 5-Amino Salicylic Acid Combinations in Experimental Colitis.

ABSTRACT: Chitosan is used in various drug delivery approaches as a pharmaceutical excipient. Although its potential as an immunomodulatory agent has been reported, its use in this capacity has not been fully explored. The efficacy of chitosan as an active pharmacological agent, particularly in anti-inflammatory therapy in inflammatory bowel diseases (IBD), was investigated in this study. The potential impact of the molecular weight (MW) and degree of deacetylation (DD) of chitosan was investigated together with 5-amino salicylic acid (5-ASA) for its efficacy in a combination anti-inflammatory therapy in murine experimental colitis. Such a combination would potentially be developed into novel dual strategies whereby chitosan acts as a mucoadhesive excipient as well as provide an additional anti-inflammatory benefit. Chitosan grades with different MW and DD were administered intrarectally alone or in combination with 5-ASA to colitis mice for 3 days. Myeloperoxidase (MPO) and alkaline phosphatase (ALP) activity and tumor necrosis factor-? (TNF-?), interleukin-6 (IL-6), interleukin-1? (IL-1?) and nuclear factor kappa-B (NF-?B) levels were assessed from the colon. Intrarectal treatment of colitis with 30 mg/kg chitosan alone and with 30 mg/kg 5-ASA for 3 days led to a significant decrease in MPO, ALP, TNF-?, IL-6, IL-1? and NF-?B in colitis mice compared to untreated mice. Surprisingly, the efficacy of chitosan as an anti-inflammatory polymer was relatively independent from its structural properties, namely DD and MW. However, combinations of chitosan with 5-ASA showed a significant pharmacological improvement, whereby the additive anti-inflammatory efficacy observed shows the possibility of finetuning chitosan by combining it with anti-inflammatory agents to optimize its anti-inflammatory potential.

SUBMITTER: Jhundoo HD

PROVIDER: S-EPMC7692366 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Anti-Inflammatory Activity of Chitosan and 5-Amino Salicylic Acid Combinations in Experimental Colitis.

Jhundoo Henusha D HD Siefen Tobias T Liang Alfred A Schmidt Christoph C Lokhnauth John J Béduneau Arnaud A Pellequer Yann Y Larsen Crilles Casper CC Lamprecht Alf A

Pharmaceutics 20201029 11

Chitosan is used in various drug delivery approaches as a pharmaceutical excipient. Although its potential as an immunomodulatory agent has been reported, its use in this capacity has not been fully explored. The efficacy of chitosan as an active pharmacological agent, particularly in anti-inflammatory therapy in inflammatory bowel diseases (IBD), was investigated in this study. The potential impact of the molecular weight (MW) and degree of deacetylation (DD) of chitosan was investigated togeth ...[more]

PMID: 33138176

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Project description:INTRODUCTION:Essential amino acid ?-keto acid analogs are used in the treatment of chronic kidney disease to delay the symptoms of uremia. However, it is unknown whether essential amino acid ?-keto acid analogs affect the oxidative stress and the inflammation in acute renal injury such as those produced by ischemia-reperfusion. OBJECTIVE:To evaluate the effect of essential amino acid ?-keto acid analogs on renal ischemia-reperfusion injury in Wistar rats. MATERIALS AND METHODS:Rats were divided into 11 groups (n=6/group): Two groups received physiological saline with or without ischemia-reperfusion injury (45 min/24 h), six groups received essential amino acid ?-keto acid analogs (400, 800, or 1,200 mg/kg/24 h/7d) with or without ischemia-reperfusion injury (essential amino acid ?-keto acid analogs + ischemia-reperfusion), and two groups received allopurinol (50 mg/kg/24 h/7d) with or without ischemia-reperfusion injury. Biochemical markers included creatinine and blood urea nitrogen (BUN), proinflammatory cytokines (IL-1?, IL-6, and TNF-?), renal damage markers (cystatin C, KIM-1, and NGAL), and markers of oxidative stress such as malondialdehyde (MDA) and total antioxidant activity. RESULTS:The essential amino acid ?-keto acid analog- and allopurinol-treated groups had lower levels of creatinine, BUN, renal damage markers, proinflammatory cytokines, and MDA than their corresponding ischemia-reperfusion groups. These changes were related to the essential amino acid ?-keto acid analogs dosage. Total antioxidant activity was lower in essential amino acid ?-keto acid analog- and allopurinol-treated groups than in the corresponding ischemia-reperfusion groups. CONCLUSIONS:This is a new report on the nephroprotective effects of essential amino acid ?-keto acid analogs against ischemia-reperfusion injury. Essential amino acid ?-keto acid analogs decreased the levels of biochemical markers, kidney injury markers, proinflammatory cytokines, and MDA while minimizing total antioxidant consumption.

Dataset Information

Anti-Inflammatory Activity of Chitosan and 5-Amino Salicylic Acid Combinations in Experimental Colitis.

Publications

Anti-Inflammatory Activity of Chitosan and 5-Amino Salicylic Acid Combinations in Experimental Colitis.

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