Gabapentin attenuates intestinal inflammation: Role of PPAR-gamma receptor

• Published in: European journal of pharmacology Vol. 873; p. 172974
• Main Authors: de Brito, Tarcisio Vieira, Júnior, Genilson José Dias, da Cruz Júnior, José Simião, Silva, Renan Oliveira, da Silva Monteiro, Carlos Eduardo, Franco, Alvaro Xavier, Vasconcelos, Daniel Fernando Pereira, de Oliveira, Jefferson Soares, da Silva Costa, Deiziane Viana, Carneiro, Theides Batista, Gomes Duarte, Antoniella Souza, de Souza, Marcellus Henrique Loiola Ponte, Soares, Pedro Marcos Gomes, Barbosa, André Luiz dos Reis
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.04.2020
• Subjects: Colitis; Gabapentin; Peroxisome-gamma; Gabapentin; Peroxisome-gamma; Colitis
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2020.172974

Gabapentin is an anticonvulsant drug that is also used for post-herpetic neuralgia and neuropathic pain. Recently, gabapentin showed anti-inflammatory effect. Nuclear factor kappa B (NFκB) is a regulator of the inflammatory process, and Peroxisome Proliferator-activated Receptor gamma (PPAR-gamma) is an important receptor involved in NFκB regulation. The aim of the present work was to study the potential role of PPAR-gamma receptor in gabapentin-mediated anti-inflammatory effects in a colitis experimental model. We induced colitis in rats using trinitrobenzenosulfonic acid and treated them with gabapentin and bisphenol A dicyldidyl ether (PPAR-gamma inhibitor). Macroscopic lesion scores, wet weight, histopathological analysis, mast cell count, myeloperoxidase, malondialdehyde acid, glutathione, nitrate/nitrite, and interleukin levels in the intestinal mucosa were determined. In addition, western blots were performed to determine the expression of Cyclooxygenase-2 (COX-2) and NFκB; Nitric Oxide Inducible Synthase (iNOS) and Interleukin 1 beta (IL-1β) levels were also determined. Gabapentin was able to decrease all inflammatory parameters macroscopic and microscopic in addition to reducing markers of oxidative stress and cytokines such as IL-1β and Tumor Necrosis Factor alpha (TNF-α) as well as enzymes inducible nitric oxide synthase and cyclooxygenase 2 and inflammatory genic regulator (NFκB). These effect attributed to gabapentin was observed to be lost in the presence of the specific inhibitor of PPAR-gamma. Gabapentin inhibits bowel inflammation by regulating mast cell signaling. Furthermore, it activates the PPAR-gamma receptor, which in turn inhibits the activation of NFκB, and consequently results in reduced activation of inflammatory genes involved in inflammatory bowel diseases.