Background: Although the pathogenic mechanisms of selective loss of motor neurons in amyotrophic lateral sclerosis (ALS) are unknown, there is increasing evidence for the hypothesis of an oxidative stress-related mitochondrial involvement as key determinant of motor neuron degeneration Objective: The aim of our study has been to assess blood levels of peroxidation markers and to relate them to in-vivo oxidative metabolism in exercising muscle in patients affected by ALS. Method: For this purpose 10 patients (seven men and three women, mean age 58.5 ± 8.2 SD), performed an incremental bicycling test for the assessment of lipoperoxides and lactate during exercise. Results: At rest, the ALS patients had higher than normal levels of both lactate (2.82 ± 0.76 mmol/L; normal range: 0.67-2.47 mmol/L) and lipoperoxides; (361.7 ± 40.2 AU; normal range: 250-320 AU), the latter corresponding to a level of moderate oxidative stress. A further increment during exercise was observed both at lactate threshold and maximal power output levels. Values of blood lipoperoxides were significantly higher (P < 0.05) than those in control patients affected by chronic motor denervating processes of different origins and related (P < 0.01) to lactate production on exercising. Conclusions: These findings indicate the occurrence of an abnormally increased size of blood free radical pool in resting conditions and during exercise in ALS patients. The relationship between the levels of reactive oxygen species and lactate production is indicative of a tight link between mitochondrial function and oxidative stress in ALS.
Impaired oxidative metabolism and lipid peroxidation in exercising muscle from ALS patients
SICILIANO, GABRIELE;BARSACCHI, RENATA;MURRI, LUIGI
2002-01-01
Abstract
Background: Although the pathogenic mechanisms of selective loss of motor neurons in amyotrophic lateral sclerosis (ALS) are unknown, there is increasing evidence for the hypothesis of an oxidative stress-related mitochondrial involvement as key determinant of motor neuron degeneration Objective: The aim of our study has been to assess blood levels of peroxidation markers and to relate them to in-vivo oxidative metabolism in exercising muscle in patients affected by ALS. Method: For this purpose 10 patients (seven men and three women, mean age 58.5 ± 8.2 SD), performed an incremental bicycling test for the assessment of lipoperoxides and lactate during exercise. Results: At rest, the ALS patients had higher than normal levels of both lactate (2.82 ± 0.76 mmol/L; normal range: 0.67-2.47 mmol/L) and lipoperoxides; (361.7 ± 40.2 AU; normal range: 250-320 AU), the latter corresponding to a level of moderate oxidative stress. A further increment during exercise was observed both at lactate threshold and maximal power output levels. Values of blood lipoperoxides were significantly higher (P < 0.05) than those in control patients affected by chronic motor denervating processes of different origins and related (P < 0.01) to lactate production on exercising. Conclusions: These findings indicate the occurrence of an abnormally increased size of blood free radical pool in resting conditions and during exercise in ALS patients. The relationship between the levels of reactive oxygen species and lactate production is indicative of a tight link between mitochondrial function and oxidative stress in ALS.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
