Doksorubisin ile Oluşturulan Deneysel İskelet Kası Atrofisi Modelinde Mitokondri Transplantasyonu ve Egzersizin Etkileri
Date
2023Author
Gökhan Burçin, Kubat
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Doxorubicin (DOX) is a chemotherapy drug that serves to treat many different forms
of cancer but has hazardous side effects. It has been demonstrated in several studies that its
toxic effect induces skeletal muscle atrophy. Exercise prevents skeletal muscle atrophy,
particularly via mitochondrial pathways, without altering DOX's antineoplastic effects. While
mitochondria transplantation may mitigate toxicity, neurological disorders, heart, kidney,
and liver damage, its effects on skeletal muscle atrophy remain unknown. The goal of the
study was to assess how exercise and mitochondrial transplantation affected recovery in a
rat model of DOX-induced skeletal muscle atrophy. In this study, male Sprague Dawley rats
were divided into control (K), DOX (D), DOX and mitochondria (DM), DOX and exercise (DE),
DOX, exercise and mitochondria (DEM) groups (n=8/group). Before receiving a dosage of
DOX, the rats in the exercise group (DE) underwent a 10-day running exercise whereas those
in the mitochondrial group (DM) received two doses of mitochondrial transplantation. In the
exercise and mitochondria group (DEM), both exercise and mitochondria transplantation
were applied together. The D, DM, DE, and DEM groups received a 20 mg/kg DOX injection
to induce muscular atrophy. MitoTracker Red CMXROS, MitoSpy Green FM, and JC-1 analysis
were performed for the membrane integrity and potential of the isolated mitochondria. In
the tibialis anterior muscle, measurement of muscle weights, histological analysis (H-E, SDH,
and PAS), immunohistochemical analysis (Caspase-3, NF-κB, DRP-1, and MFN-2), biochemical
analysis of blood samples (urea, LDH, ALT, and AST) and oxidative stress analysis (TAS and
TOS) were performed. When the tibialis anterior muscle weights of the groups were
compared DE and DEM groups increased significantly compared to the K group (P < 0.05).
When the final body weights were compared, the DM, DE, and DEM groups increased
significantly compared to the D group (P < 0.05). For the tibialis anterior cross-sectional area,
the D group decreased compared to the K group, DE and DEM groups increased compared to
the D group (P < 0.05). SDH levels were found to be significantly higher in all groups compared
to the group D (P < 0.05). Urea levels were higher in D and DM groups compared to the K
group, but significantly lower in the DE group (P < 0.05), and ALT levels were significantly
higher in DM, DE, DEM groups compared to the K group (P < 0.05). Caspase-3 level was found
to be significantly higher in D and DM groups compared to DE and DEM groups (P < 0.05),
while NF-kB level was higher in D group than K group, and lower in DM, DE, DEM groups
compared to D group (P < 0.05). DRP-1 level was higher in D and DE groups than K group and
was lower in DM and DEM groups than D group (P < 0.05). MFN-2 level was higher in DM and
DE groups than the K group and was higher in the DE group than the D group (P < 0.05). DE
group was lower than K and DM groups in the TOS analysis, while DE and DEM groups were
higher than the K group in the TAS analysis (P < 0.05). These results demonstrated that the
role of exercise in preventing muscle atrophy is important, but it is more effective with
mitochondria transplantation.