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Simple Summary: Muscle wasting and cachexia are common in patients with cancer. Several mechanisms underlie muscle physiological and structural alterations in cancer-induced cachexia. Poly (ADPribose) polymerases (PARPs) are involved in muscle metabolism and in cancer. Selective inhibitors of PARP activity improve muscle function and structure. This study sought to investigate whether rucaparib (PARP inhibitor) may attenuate muscle damage in a mouse model of lung-cancer-induced cachexia. Rucaparib was administered to cancer-cachectic mice. Physiological and biological parameters were determined in the respiratory and limb muscles of the animals. In cancer cachexia mice compared to non-cachexia controls, body weight and body weight gain, muscle weight, limb strength, physical activity, and muscle fiber size significantly declined, while levels of PARP activity, plasma troponin I, muscle damage, and proteolytic and autophagy markers increased. Treatment with rucaparib elicited a significant improvement in body weight gain, tumor size and weight, physical activity, muscle damage, troponin I, and proteolytic and autophagy levels. Overactivation of poly (ADPribose) polymerases (PARPs) is involved in cancer-induced cachexia. We hypothesized that the PARP inhibitor rucaparib may improve muscle mass and reduce damage in cancer cachexia mice. In mouse diaphragm and gastrocnemius (LP07 lung adenocarcinoma) treated with PARP inhibitor (rucaparib,150 mg/kg body weight/24 h for 20 days) and in non-tumor control animals, body, muscle, and tumor weights; tumor area; limb muscle strength; physical activity; muscle structural abnormalities, damage, and phenotype; PARP activity; and proteolytic and autophagy markers were quantified. In cancer cachexia mice compared to non-cachexia controls, body weight and body weight gain, muscle weight, limb strength, physical activity, and muscle fiber size significantly declined, while levels of PARP activity, plasma troponin I, muscle damage, and proteolytic and autophagy markers increased. Treatment with the PARP inhibitor rucaparib elicited a significant improvement in body weight gain, tumor size and weight, physical activity, muscle damage, troponin I, and proteolytic and autophagy levels. PARP pharmacological inhibition did not exert any significant improvements in muscle weight, fiber size, or limb muscle strength. Treatment with rucaparib, however, improved muscle damage and structural abnormalities and physical activity in cancer cachexia mice. These findings suggest that rucaparib exerts its beneficial effects on cancer cachexia performance through the restoration of muscle structure. [ABSTRACT FROM AUTHOR]

Abstract: Cigarette smoke (CS)-induced oxidative stress may cause muscle alterations in chronic conditions such as chronic obstructive pulmonary disease (COPD). We sought to explore in AKR/J mice exposed to CS for 6 months and in control animals, levels of protein oxidation, oxidized proteins (immunoblotting, proteomics) and antioxidant mechanisms in both respiratory and limb muscles, body weight modifications, systemic inflammation, and lung structure. Compared to control mice, CS-exposed animals exhibited a reduction in body weight gain at 3 months and thereafter, showed lung emphysema, and exhibited increased oxidative stress levels in their diaphragms and gastrocnemius at 6 months. Proteins involved in glycolysis, ATP production and distribution, carbon dioxide hydration, and muscle contraction were carbonylated in respiratory and limb muscles. Blood tumor necrosis factor (TNF)-alpha levels were significantly greater in CS-exposed mice than in control animals. In AKR/J mice, chronic exposure to CS induces lung emphysema concomitantly with greater oxidative modifications on muscle proteins in both respiratory and limb muscles, and systemic inflammation. [Copyright &y& Elsevier]

Abstract: Oxidative stress is involved in the sarcopenia of aging muscles. On the grounds that ventilatory muscles are permanently active, and their activity may even increase with aging, we hypothesized that the levels of oxidative stress would probably be increased in the external intercostals of elderly healthy individuals. We conducted a case–control study in which reactive carbonyl groups, malondialdehyde–protein adducts, 3-nitrotyrosine immunoreactivity, Mn-superoxide dismutase (Mn-SOD), and catalase were detected using immunoblotting in external intercostals and quadriceps (open muscle biopsies) obtained from 12 healthy elderly and 12 young individuals of both sexes. In elderly subjects, reactive carbonyls, malondialdehyde–protein adducts, 3-nitrotyrosine, Mn-SOD, and catalase were significantly greater in the external intercostals than in the young controls. A post hoc analysis, in which men and women from both groups were analyzed separately, revealed that the external intercostals of elderly women, but not those of elderly men, showed significantly increased levels of reactive carbonyls, malondialdehyde–protein adducts, 3-nitrotyrosine, and Mn-SOD compared to those of control females. This study suggests that differences in muscle activity might explain the differential pattern of oxidative stress observed in human respiratory and limb muscles with aging as well as the likely existence of a sex-related regulation of this phenomenon in these muscles. [Copyright &y& Elsevier]