Asetil L-karnitin ve doksorubisinin rat çizgili kası üzerine etkilerinin araştırılması

Aim. Doxorubicin is a widely used anticancer agent which can cause an unpredictable cardiac toxicity increases with its cumulative dose. Previous studies demonstrated that side effects of doxorubicin can be reduced by L-carnitine. However in only a few studies, toxic effects of doxorubicin on skeletal muscles was investigated widely. The objective of present study was to investigate the effects of doxorubicin and Acetyl L-carnitine on skeletal muscles in rats. Method. The study was performed on adult male Wistar-Albino rats which are 200-300 gr in weight. Rats were divided to four groups as control, doxorubicine, ALCAR and ALCAR + doxorubicine. The first group (n=7) was the control. The second and forth groups (n=6/n=6) received intraperitoneal doxorubicine (cumulative dose 15 mg/kg). Third and forth groups (n=7/n=6) received intraperitoneal ALCAR (300 mg/kg/day) and it was continued 10 days. All animals in each group were sacrificed on tenth day of the study and muscle biopsy samples were taken from quadriceps muscles. All samples were frozen and 8-micron sections were cut using cryostat. Slides were stained with routine hematoxylin eosin, enzyme histochemically combined COX and SDH, histochemically with modified Gomori’s trichrome, PAS and oil red O. Fast myosin antibody was used for discriminating myofiber type. Results. No significant differences were found in muscle fiber type distribution, lipid and glucogen accumulation, or mitocondrial function in Doxorubicine or ALCAR groups compared with control group. Conclusion. This study indicated that treatment with doxorubicine or ALCAR cannot produce significant injury to non-cardiac striated muscle tissue.

Özet

Amaç. Doksorubisin, ilacın birikmiş dozuna bağlı olarak öngörülemeyen kardiotoksisiteye yol açan, yaygın olarak kullanılan bir kanser ilacıdır. Önceki çalışmalar doxorubicinin bu yan etkisinin L-karnitin ile azaldığını göstermiştir. Ancak sadece az sayıda çalışmada doksorubisinin iskelet kası üzerine toksik etkisi ayrıntılı olarak irdelenmiştir. Bu çalışmanın amacı, doksorubisin ve asetil L-karnitinin sıçan çizgili kasındaki etkilerinin araştırılmasıdır. Yöntem. Çalışma, ağırlıkları 200-300 g arasında değişen erişkin erkek Wistar- Albino şıçanlar üzerinde gerçekleştirildi. Sıçanlar kontrol, doksorubisin, ALKAR ve doksorubisin + ALKAR olmak üzere 4 gruba ayrıldı. İlk grup (n=7) kontrol grubuydu. İkinci ve dördüncü gruba (n=6/ n=6) intraperitoneal doksorubusin verildi (kümülatif doz 15mg/kg). Üçüncü ve dördüncü gruba (n=7/ n=6) 10 gün süreyle intraperitoneal ALKAR verildi (300 mg/kg/gün). Tüm hayvanlar çalışmanın 10. günü sakrifiye edildi ve kuadriseps kasından kas biyopsi örnekleri alındı. Tüm örnekler donduruldu ve kriyostatla 8- mikronluk kesitler yapıldı. Tüm preparatlar rutin hematoksilen eozin boyasıyla, kombine COX- SDH enzim boyalarıyla ve histokimyasal modifiye Gomori trikrom, PAS ve oil red O boyalarıyla boyandı. Myofiber tip ayrımı için fast myozin antikoru kullanıldı. Bulgular. Kontrol grubuyla karşılaştırıldığında, kas fiber tip dağılımı, lipit ve glikojen depolanması ile mitokondrial fonksiyonlar açısından doksorubisin veya ALKAR grubunda anlamlı fark bulunmadı. Tartışma. Bu çalışma doksorubisin veya ALKAR tedavisinin kalp-dışı çizgili kas dokusunda önemli incinmeye etken olmadığını göstermiştir.

Anahtar sözcükler: Doksorubisin, ALKAR, iskelet kası, sıçan

 

Abstract

Aim. Doxorubicin is a widely used anticancer agent which can cause an unpredictable cardiac toxicity increases with its cumulative dose. Previous studies demonstrated that side effects of doxorubicin can be reduced by L-carnitine. However in only a few studies, toxic effects of doxorubicin on skeletal muscles was investigated widely. The objective of present study was to investigate the effects of doxorubicin and Acetyl L-carnitine on skeletal muscles in rats. Method. The study was performed on adult male Wistar-Albino rats which are 200-300 gr in weight. Rats were divided to four groups as control, doxorubicine, ALCAR and ALCAR + doxorubicine. The first group (n=7) was the control. The second and forth groups (n=6/n=6) received intraperitoneal doxorubicine (cumulative dose 15 mg/kg). Third and forth groups (n=7/n=6) received intraperitoneal ALCAR (300 mg/kg/day) and it was continued 10 days. All animals in each group were sacrificed on tenth day of the study and muscle biopsy samples were taken from quadriceps muscles. All samples were frozen and 8-micron sections were cut using cryostat. Slides were stained with routine hematoxylin eosin, enzyme histochemically combined COX and SDH, histochemically with modified Gomori’s trichrome, PAS and oil red O. Fast myosin antibody was used for discriminating myofiber type. Results. No significant differences were found in muscle fiber type distribution, lipid and glucogen accumulation, or mitocondrial function in Doxorubicine or ALCAR groups compared with control group. Conclusion. This study indicated that treatment with doxorubicine or ALCAR cannot produce significant injury to non-cardiac striated muscle tissue.

Keywords: Doxorubicin, ALCAR, skeletal muscle, rat