Voluntary Wheel Running Reduces the Acute Inflammatory Response to Liver Carcinogen in a Sex-specific Manner

Abstract

Inflammation contributes to the development of cancer, yet acute inflammatory responses are also needed to eradicate tumorigenic cells and activate adaptive immune responses to combat cancer. Physical exercise has direct immunomodulatory effects, and in line with this, exercise has been demonstrated to inhibit tumor growth, including diethylnitrosamine-(DEN)-induced hepatocarcinoma. Having observed a sex-dependent development of DEN-induced hepatocarcinoma, we aimed to evaluate the effect of exercise and sex on the acute inflammatory response to DEN. Thus, we randomized male and female mice to cages with or without running wheels for 6 weeks, whereafter DEN was administered and the inflammatory response was evaluated for up to 96 hours. DEN administration caused marked acute inflammatory responses in female mice with weight loss, reduced food intake, release of liver enzymes, and increased systemic levels of IL6. Moreover, DEN caused increased hepatic expression of cytokines, immune cell markers, and components of the toll-like receptor signaling pathway. In male mice, DEN administration provoked similar physiologic effects with weight loss and reduced food intake, but less systemic and hepatic acute inflammation, which was associated with a higher baseline expression of the detoxifying enzyme glutathione S-transferase and lower expression of ERα in male mice. Voluntary wheel running attenuated systemic and hepatic inflammation, in particular in the female mice, and shifted the peak time of the inflammatory response. In conclusion, DEN elicited an acute inflammatory response in particular in female mice, and this response was attenuated by prior exercise. .

Voluntary exercise in mesothelioma: effects on tumour growth and treatment response in a murine model

“…Exercise induced suppression of tumour initiation and growth may be mediated by effects on tumour metabolism and immune function. Inflammation is critical in cancer development and VE has been shown to attenuate the inflammatory response in mice following carcinogen exposure, promoting more efficient clearance of damaged cells [14]. Additionally, VE decreases tumour incidence and growth via regulation of key immune cells, including natural killer (NK) and effector lymphocytes [13].…”

The effect of voluntary wheel running on the antioxidant status is dependent on sociability conditions

“…Running wheel exposure is commonly employed as a voluntary PA model in rodents, since this protocol is uncomplicated, easy, and results in a quantifiable measure of PA ( Sherwin, 1998 ). Although there is no consensus on the ground mechanisms controlling running wheel activity ( Novak et al, 2012 ), use of a running wheel increases the average rodent life expectancy by nearly 10% ( Holloszy, 1998 ); produces antidepressant- and anxiolytic-like effects ( Cunha et al, 2013 ; Mazur et al, 2017 ), which are paralleled to adult neurogenesis and neuronal survival ( van Praag et al, 1999a , van Praag et al, 1999b ); cardioprotection ( Bronikowski et al, 2003 ; Naderi et al, 2015 ); hepatoprotection ( Bay et al, 2017 ; Zolfagharzadeh and Roshan, 2013 ); and skeletal muscle trophism ( Brooks et al, 2018 ; Takigawa et al, 2019 ). Studies have indicated that running wheel exposition exerts its positive effects on health through a variety of biological pathways, but the exact mechanisms underlying its influences on health are not fully determined.…”

Voluntary Exercise in Mesothelioma: Effects on Tumour Growth and Treatment Response in a Murine Model

“…In ammation is critical in cancer development and VE has been shown to attenuate the in ammatory response in mice following carcinogen exposure, promoting more e cient clearance of damaged cells [14]. Additionally, VE decreases tumour incidence and growth via regulation of key immune cells, including natural killer (NK) and effector lymphocytes [13].…”