Low-dose curcumin reduced TNBS-associated mucin depleted foci in mice by scavenging superoxide anion and lipid peroxides, rebalancing matrix NO synthase and aconitase activities, and recoupling mitochondria

The research article “Low-dose curcumin reduced TNBS-associated mucin depleted foci in mice by scavenging superoxide anion and lipid peroxides, rebalancing matrix NO synthase and aconitase activities, and recoupling mitochondria”, co-authored by METU member Prof. Sreeparna Banerjee, has been published in Inflammopharmacology.

Background: The role of mitochondrial dysfunction in the pathogenesis of inflammatory bowel diseases (IBD) is still being investigated. This study evaluated the therapeutic effect of curcumin (Cur), a polyphenolic electrophile in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced chronic colitis and mitochondrial dysfunction, in mice. Methods: Colitis was induced by rectal instillation to mice of 30 mg kg⁻¹ TNBS, alone or followed by daily intraperitoneal injections of Cur 25 mg kg⁻¹. Animals were euthanized at days 3, 7, and 14, post TNBS challenge. Colon mitochondria of control mice were treated with 5 µM Cur, and TNBS (50, 100 µM)-toxicity was evaluated by measuring swelling, respiration, and aconitase and fumarase activities. Redox status was evaluated in colon mucosa and in mitochondria. Results: In vitro, a short-term Cur treatment controlled the dose and time dependent mitochondrial toxicity induced by TNBS, by collapsing the generation of superoxide anion and hydroperoxy lipids, rebalancing nitric oxide synthase and aconitase activities, and recoupling mitochondria. In vivo, a daily low-dose Cur abolished mice mortality which reached 27% in model group. Cur improved in a time dependent manner mucosal redox homeostasis, cell apoptosis, mucin depleted crypts and crypt abscesses by controlling prooxidant activity of myeloperoxidase and NO synthase associated to phagocytes influx, quenching hydroperoxy lipids, and reboosting GSH levels. Conclusion: Cur, by quenching intra and extra mitochondrial ROS generation, rebalancing aconitase/fumarase and MDA/GSH ratios, and recoupling mitochondria, may support mithormesis priming and remitting in IBD.

Mouzaoui, S., Banerjee, S., & Djerdjouri, B. (2020). Low-dose curcumin reduced TNBS-associated mucin depleted foci in mice by scavenging superoxide anion and lipid peroxides, rebalancing matrix NO synthase and aconitase activities, and recoupling mitochondria. Inflammopharmacology, 28(4), 949-965. doi:10.1007/s10787-019-00684-4

Article access: https://link.springer.com/article/10.1007%2Fs10787-019-00684-4

Keywords:

Aconitase; Curcumin; Electrophile; MDA/GSH; Mucin depleted crypts; TNBS

Other authors:
Mouzaoui, S. & Djerdjouri, B. (METU)