Effects of human Umbilical Cord Stem Cells and Granulocyte Colony- Stimulating Factor (G-CSF) on Carbon Tetrachloride-Induced Nephrotoxicity

Abstract

Background: Recently, stem cells have been used to facilitate healing in animal models of renal failure induced by acute ischemic and nephrotoxic damage. Granulocyte colony-stimulating factor (G-CSF) has been reported to stimulate stem cell mobilization from bone marrow and these cells may contribute to renal repair.Objectives: In the present study, the effects of G-CSF and stem cell administration as monotherapy or in combination, and the relation of these effects with the duration of therapy, have been investigated in an experimental rat model of carbon tetrachloride (CCl4)-induced nephrotoxicity.Materials and Methods: The fifty rats included in the study were distributed into 4 main groups, Group 1, 2, 3, and 4, and two subgroups for each group, except for Group 1. All rats received an intraperitoneal injection of CCl4. Then at 6 h, Groups 1, 2a, 3a, and 4a were administered saline, stem cells, G-CSF, and stem cell plus G-CSF, respectively. At 24 h, Groups 2b, 3b, and 4b were administered stem cells, G-CSF, and stem cell plus G-CSF, respectively. All animals were sacrificed 48 h after the CCl4 injections. Serum urea, creatinine, sodium, and potassium levels were measured from blood samples. Tissue α-glutathione S-transferase (GST) levels were also measured from renal tissues.Results: Serum urea was reduced in all groups when compared to Group 1, but the decrease was statistically significant only in Group 3b (P = 0.04). Serum creatinine and sodium levels were similar in all groups (P > 0.05). Tissue GST levels were lower in all groups, but the reduction was significant only in Group 4a, which was administered stem cells + G-CSF at 6 h (P = 0.01). Tubular degeneration and/or tubular dilatation were the most common pathologic changes, and their incidence was similar in all groups (P > 0.05).Conclusions: Although both stem cell and G-CSF monotherapy led to damage reduction, the effect was not significant. However, the reduced damage by the combined use of stem cells and G-CSF, particularly during the early period, was statistically significant.

Transforming Growth Factor-β1/Smad3 Signaling and Redox Status in Experimentally Induced Nephrotoxicity: Impact of Carnosine

“…Carbon tetrachloride (CCl4) is one of the chlorinated hydrocarbons with wide spread use in various industries so it is considered as an environmental toxin because of its leakage into air, water and soil. Hepatic and renal tubular necrosis is the typical manifestation of CCl4-intoxication however; the pathogenesis of CCl4-induced renal damage remains largely elusive [1]. CCl4 acts through activation of phase I cytochrome P450 system especially cytochrome P450 2E1 (CYP2E1) with formation of reactive metabolites as trichloromethyl radicals ( Á CCl 3 ) and peroxy trichloromethyl radicals ( Á OOCCl 3 ).…”