L‐glutathione 1% promotes neuroprotection of nitrergic neurons and reduces the oxidative stress in the jejunum of rats with Walker‐256‐bearing tumor

• Published in: Neurogastroenterology and motility Vol. 35; no. 12; pp. e14688 - n/a
• Main Authors: Oliveira, Ana Paula, Perles, Juliana Vanessa Colombo Martins, Souza, Sara Raquel Garcia, Sestak, Sabrina Silva, Motta Lima, Fabiana Galvão, Almeida, Gustavo Henrique Doná Rodrigues, Cicero, Lídia Rodrigues, Clebis, Naianne Kelly, Guarnier, Flávia Alessandra, Blegniski, Fernanda Pascoal, Vasconcelos, Roseane Carvalho, Araújo, Aurigena Antunes, Comar, Jurandir Fernando, Moreira, Lucas Stafuza, Sehaber‐Sierakowski, Camila Cavicchioli, Zanoni, Kassio Papi Silva, Zanoni, Jacqueline Nelisis
• Format: Journal Article
• Language: English
• Published: Oxford Wiley Subscription Services, Inc 01.12.2023
• Subjects: antioxidant; cancer; cytokines; Enteric nervous system; Glutathione; Inflammation; Inoculation; Jejunum; Myenteric plexus; neoplasia; Neurons; Neuroprotection; Nitrotyrosine; Oxidative stress; reactive species; Small intestine; Tumors
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1111/nmo.14688

Aims Our main goals were to investigate the effects of L‐glutathione (1%) treatment in Walker‐256 tumor‐bearing rats by analyzing immunoreactive neurons (IR), responsive to the nNOS enzyme and 3‐Nitrotyrosine, in their jejunum myenteric plexus. Moreover, the oxidative state and inflammatory process in these animals were investigated. Methods Four experimental groups were utilized: control (C), control treated with L‐glutathione (CGT), Walker‐256 tumor‐bearing rats (TW), and Walker‐256 tumor‐bearing rats treated with L‐glutathione (TWGT). After 14 days of tumor inoculation, the jejunum was collected for immunohistochemical techniques and assessment of oxidative status. Plasma was collected to evaluate oxidative status and measure cytokines. Results The TW group exhibited a decrease of reduced glutathione in their jejunum, which was prevented in the L‐glutathione treated TWGT group. TW animals presented pronounced oxidative stress by increasing levels of lipoperoxidation in their jejunum and malondialdehyde in their plasma; however, the L‐glutathione treatment in TWGT group was not able to avoid it. The total antioxidant capacity was altered in groups TW and TWGT, yet the last one had a better index in their plasma. The IL‐10, and TNF‐α levels increased in TWGT animals. The nNOS‐IR neuron density decreased in the jejunum myenteric plexus of the TW group, which was avoided in the TWGT group. The nNOS +3‐Nitrotyrosine neurons quantification did not show significative alterations. Conclusion The treatment with L‐glutathione (1%) imposed an important defense to some parameters of oxidative stress induced by TW‐256, leading to neuroprotection to the loss in the nNOS‐IR neuron density. Walker‐256 tumor‐bearing rats showed a reduction in the neuronal subpopulation nNOS‐IR in the myenteric plexus. In this context, treatment with 1% L‐glutathione was effective in preventing significant changes in the neuronal density of this subpopulation in Walker‐256 tumor‐bearing rats. Treatment with 1% L‐glutathione in healthy rats indicated a decrease in the density of nNOS‐IR neurons in the myenteric plexus, demonstrating that the use of this substance in a healthy organism can be harmful to the enteric nervous system.