Ameliorating role of co-administration of granulocyte colony stimulating factor and sodium bicarbonate on the skeletal muscle of a rat model of chronic kidney disease (A histological and immunohistochemical study)

Abstract

Over half million individuals suffer from chronic kidney disease (CKD) worldwide. In addition to raising the possibility of cardiovascular diseases, skeletal myopathy remains a challenging complication that is highly correlated with mortality and a lower quality of life. Granulocyte-colony stimulating factor (G-CSF) is an active cytokine for mobilization of immunological and hematopoietic stem cells that can replace exogenous stem cell infusions. So, it is seen as a less expensive and noninvasive tool for regenerative medicine. Sixty three rats were divided into 4 groups: I control, II CKD induced, IIIa, IIIb treated and IV recovery groups. After induction of CKD in all rats, group II were sacrificed after 4 weeks. Rats of group IIIa received NaHCO₃. Group IIIb rats were injected subcutaneously by G-CSF as 100 µg/kg/day for 5 successive days in addition to NaHCO₃ as group IIIa. Group IV rats were housed for 4 weeks without treatment. Serum urea, creatinine, tissue MDA& TNF-α were assessed. Renal and gastrocnemius muscle sections were evaluated for histological structure, CD34 and myogenin immune expression, morphometric and statistical analyses. The CKD group revealed a significant increase in MDA and TNF-α. Furthermore, features of renal injury, muscle degenerative changes, increased collagen and decreased CD34 and myogenin expression were observed. Alterations were partially attenuated by NaHCO₃, while GCSF remarkably improved most parameters. The current results indicated that co-administration of GCSF and NaHCO₃ could ameliorate CKD myopathy via attenuating oxidative stress, immunomodulation, pro-angiogenic ability, myocyte regeneration. In addition to the reduction of mitochondrial stress and maintenance of cellular homeostasis.