Resistance exercise prevents impaired homocysteine metabolism and hepatic redox capacity in Walker-256 tumor-bearing male Wistar rats

• In the present study, we proposed a resistance exercise experimental model to prevent perturbation in homocysteine (Hcy) metabolism promoted by Walker-256 tumor growth.
• Twelve days of Walker-256 tumor cell inoculation promoted impaired Hcy metabolism, hepatic oxidative stress, and liver injury.
• Resistance exercise training before tumor cell inoculation prevents cancer-associated Hcy accumulation and redox imbalance.
• The regulatory effects of resistance exercise on Hcy metabolism appear to be at the level of transsulfuration for glutathione synthesis.

ObjectiveThe aim of this study was to investigate changes in homocysteine (Hcy) metabolism and redox balance in response to exercise treatment in a tumor-bearing rat model.MethodsMale Wistar rats were exposed, or not, to a resistance exercise program 6 wk before inoculation with Walker-256 tumor cells or vehicle. After application, rats maintained their routine for 12 d and were then sacrificed for plasma and liver analyses.ResultsImpaired Hcy metabolism was evident after 12 d of tumor cell inoculation as demonstrated by significantly increased (P < 0.05) plasma total homocysteine (tHcy) concentration (53%) and decreased plasma cysteine, methionine, and vitamin B12 concentrations. Decreased hepatic cystathionine β-synthase (CBS) and betaine-homocysteine S-methyltransferase mRNA levels were found in tumor-bearing rats but not in controls. Tumor inoculation also decreased levels of liver reduced glutathione (GSH) and increased hepatic oxidative stress compared with non-tumor controls. However, resistance exercise prevented the tumor-impaired transsulfuration pathway as demonstrated by the decreased plasma tHcy, hepatic CBS expression, and increased GSH in tumor-exercised versus tumor-sedentary rats. Remarkably, all measures of liver oxidative stress were suppressed by exercise training. Tumor weight was unchanged between groups.ConclusionResistance exercise prevented tHcy accumulation and liver oxidative damage caused by Walker-256 tumor cell inoculation; the modulatory effects of resistance exercise on Hcy metabolism appear to be at the level of transsulfuration pathway.