title: Dosing-time dependent oxidative effects of an immunosuppressive drug "Mycophenolate Mofetil" on rat kidneys.
abstract: This study investigates whether the toxicity in kidneys as well as oxidative stress varied according to the dosing time of an immunosuppressive agent "mycophenolate mofetil (MMF)" in Wistar Rat. 300mg/kg of MMF was injected by intraperitonal at four different circadian stages (1, 7, 13 and 19h after light onset, HALO). Rats were sacrificed after 3days, and the kidneys were removed for determination of oxidative stress and histological analysis. Biochemical variable (creatinine, urea) was performed. Statistical analysis showed that MMF administration at 7 HALO produced a renal toxicity assessed by the significant increase in both blood creatinine and urea and antioxidant activity assessed by malondialdehyde and protein carbonyl levels indicating an induction of lipid peroxidation in oxidative damage. Whereas, at this time MMF induced a decrease the enzyme activities of renal catalase and superoxide dismutase, with a renal histopathology alterations (glomerular atrophy and lesions within proximal tubules). However, when MMF was injected in the middle of the dark-activity phase it produced a very mild renal toxicity and low oxidative stress. The obtained data indicate that the maximum of renal toxicity is observed when MMF was injected in the middle of the light- rest span in rats.
authors.affiliation: Laboratory of Pharmacology, Faculty of Medicine, University of Monastir, Monastir, Tunisia. Electronic address: dridi.ichrak@yahoo.fr.
authors.forename: Ichrak
authors.initials: I
authors.lastname: Dridi
authors.affiliation: Laboratory of Pharmacology, Faculty of Medicine, University of Monastir, Monastir, Tunisia.
authors.forename: Wafa
authors.initials: W
authors.lastname: Ben-Cherif
authors.affiliation: Laboratory of Bioresources, Biology Integrative and Valorization, Higher Institute of Biotechnology of Monastir, University of Monastir, Tunisia.
authors.forename: Hassiba
authors.initials: H
authors.lastname: Chahdoura
authors.affiliation: Laboratory of Histology Embryology and Cytogenetic, Faculty of Medicine, University of Monastir, Monastir, Tunisia.
authors.forename: Zohra
authors.initials: Z
authors.lastname: Haouas
authors.affiliation: Laboratory of Biomonitoring of the Environment, Faculty of Science of Bizerte, Carthage University, Tunis, Tunisia.
authors.forename: Mossadok
authors.initials: M
authors.lastname: Ben-Attia
authors.affiliation: Laboratory of Pharmacology, Faculty of Medicine, University of Monastir, Monastir, Tunisia.
authors.forename: Karim
authors.initials: K
authors.lastname: Aouam
authors.affiliation: Unit of Chronobiology, Foundation A. de Rothschild Paris, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Reinberg
authors.affiliation: Laboratory of Pharmacology, Faculty of Medicine, University of Monastir, Monastir, Tunisia.
authors.forename: Naceur A
authors.initials: NA
authors.lastname: Boughattas
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007674:Kidney Diseases / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014508:Urea / Q000097:blood
chemical_list: D000975:Antioxidants; D007166:Immunosuppressive Agents; D014508:Urea; D003404:Creatinine; D002374:Catalase; D013482:Superoxide Dismutase; D009173:Mycophenolic Acid
keywords: Circadian rhythm; Immunosuppressive agent; Kidney; MMF; Oxidative stress; Rats