title: The evaluate and compare the effects of the Tacrolimus and Sirolimus on the intestinal system using an intestinal cell culture model.
abstract: Tacrolimus (TAC) and Sirolimus (SRL) are produced by Streptomyces sp and effective immunosuppressive drugs commonly used in organ transplantation. Therefore, strategies for minimizing the toxicity of immunosuppressant molecules are our interest. This study was conducted to evaluate the interactive effects and the possible underlying mechanism of TAC and SRL on HCT116 cells. It was found that TAC and SRL alone inhibited cell viability. Also, it induced reactive oxygen species (ROS) formation, loss of mitochondrial membrane potential (Δψm), and able to increase DNA fragmentation in a concentration-dependent manner. The use of combined SRL and TAC showed a reservation in all toxicity observed with the two immunosuppressive drugs separately. Our result demonstrated that the mechanisms of TAC and SRL at high concentration are closely connected with oxidative stress. Furthermore, SRL at low concentration plays a protective effect against TAC (IC50) which induced cytotoxicity and genotoxicity. However, using the combination of the SRL/TAC at high concentrations (IC30) appears as an antagonist response.
authors.affiliation: a Laboratory of Research on Biologically Compatible Compounds , Faculty of Dental Medicine, University of Monastir , Monastir , Tunisia and.
authors.forename: Hanen
authors.initials: H
authors.lastname: Ferjani
authors.affiliation: a Laboratory of Research on Biologically Compatible Compounds , Faculty of Dental Medicine, University of Monastir , Monastir , Tunisia and.
authors.forename: Haila
authors.initials: H
authors.lastname: El Abassi
authors.affiliation: a Laboratory of Research on Biologically Compatible Compounds , Faculty of Dental Medicine, University of Monastir , Monastir , Tunisia and.
authors.forename: Intidhar
authors.initials: I
authors.lastname: Ben Salem
authors.affiliation: b Department of Nephrology , Dialysis and Transplant, University Hospital of Sahloul , Sousse , Tunisia.
authors.forename: Yosra
authors.initials: Y
authors.lastname: Guedri
authors.affiliation: a Laboratory of Research on Biologically Compatible Compounds , Faculty of Dental Medicine, University of Monastir , Monastir , Tunisia and.
authors.forename: Salwa
authors.initials: S
authors.lastname: Abid
authors.affiliation: b Department of Nephrology , Dialysis and Transplant, University Hospital of Sahloul , Sousse , Tunisia.
authors.forename: Abedallatif
authors.initials: A
authors.lastname: Achour
authors.affiliation: a Laboratory of Research on Biologically Compatible Compounds , Faculty of Dental Medicine, University of Monastir , Monastir , Tunisia and.
authors.forename: Hassen
authors.initials: H
authors.lastname: Bacha
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D053938:DNA Fragmentation; D004359:Drug Therapy, Combination; D045325:HCT116 Cells; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007422:Intestines / Q000166:cytology*; D015227:Lipid Peroxidation; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015394:Molecular Structure; D017382:Reactive Oxygen Species; D020123:Sirolimus / Q000737:chemistry / Q000633:toxicity*; D016559:Tacrolimus / Q000737:chemistry / Q000633:toxicity*
chemical_list: D007166:Immunosuppressive Agents; D017382:Reactive Oxygen Species; D020123:Sirolimus; D016559:Tacrolimus
keywords: Antagonism effect used; Sirolimus; Tacrolimus; intestinal cell line; toxicity