Three Weeks of Environmental Enrichment Enhance Hepatic-Muscular Oxidative Balance and decrease interleukin-6 levels in Juvenile Female C57BL/6 Mice

Débora Eduarda da Silva Fidélis^1,2,3Matheus Santos De Sousa Fernandes^1,2,3*Tiago Lacerda Ramos^1,2,3Clarice Beatriz Gonçalves Silva^1,2Allifer Rosendo Perreira^1,4Cássia Giselle de Olivera Nóbrega^1,2Valdênia Maria Oliveira de Souza^1,2Fatma Hilal Yagin^5*Yalin Aygun⁶Claudia Lagranha^1,7Mariana Pinheiro Fernandes^1,7Reem Alwhaibi⁸Fabricio Oliveira Souto^1,2,3*

• ¹Federal University of Pernambuco, Recife, Brazil
• ²Keizo Asami Institute, Federal University of Pernambuco, Recife, Pernambuco, Brazil, Recife, Brazil
• ³Postgraduate Program in Biology Applied to Health, Federal University of Pernambuco, Recife, Pernambuco, Brazil, Recife, Brazil
• ⁴Laboratory of Biochemistry and Molecular Biology of Physical Exercise, Academic Center of Vitoria de Santo Antão, Federal University of Pernambuco, Vitoria de Santo Antao, Brazil
• ⁵Department of Biostatistics, Faculty of Medicine, Malatya Turgut Özal University, Malatya, Turkey, Malatya, Türkiye
• ⁶Department of Sport Management, Faculty of Sport Sciences, Inonu University, 44280, Malatya, Türkiye, Malatya, Türkiye
• ⁷Laboratory of Biochemistry and Molecular Biology of Physical Exercise, Academic Center of Vitoria de Santo Antão, Federal University of Pernambuco, Brazil, Vitoria de Santo Antao, Brazil
• ⁸Department of Rehabilitation Sciences, College of Health and Rehabilitation Sciences, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia., Riyadh, Saudi Arabia

The Environmental Enrichment (EE) promotes systemic responses through social, cognitive, sensory, and physical stimuli. However, its effects on hepatic and muscle oxidative balance, as well as on serum inflammation markers, remain unclear. Therefore, this study aimed to evaluate whether three weeks of EE could modulate hepatic and muscular oxidative balance and the inflammatory response in female C57BL/6 mice. The animals were divided into two groups: EE (n = 13) and Standard Environmental (SE, n = 11) from postnatal day 35 to 60. The EE setting included inanimate objects such as tunnels, ladders, and toys made of both wood and plastic. After three weeks, the mice were euthanized for the withdrawal of the liver, extensor digitorum longus (EDL), soleus, and blood samples. EE significantly reduced body weight and malondialdehyde levels in the liver, soleus, and EDL muscles. Additionally, carbonyl levels decreased in the liver and soleus. Acute EE exposure enhanced enzymatic antioxidant activity (SOD, CAT, and GST) across all tissues, except for catalase activity in the EDL, which showed no significant difference between groups. Non-enzymatic defenses were improved, with reduced oxidized glutathione (GSSG) levels in the liver and soleus. Furthermore, EE increased the REDOX status in the liver and EDL. Sulfhydryl levels increased only in the liver. Finally, serum cytokine analysis revealed a significant reduction only in IL-6 levels. These findings suggest that three weeks of EE can modulate hepatic and muscular oxidative balance, as well as serum IL-6 levels, in juvenile female mice.