Circadian variation in haematological toxicity of the immunosuppressive agent "Mycophenolate Mofetil" in rats

Dridi, Ichrak; Ben-Cherif, Wafa; Aouam, Karim; Hassine, Mohsen; Ben‐Attia, Mossadok; Reinberg, A; Boughattas, Naceur A.

doi:10.2478/v10136-012-0024-9

Cited by 12 publications

(3 citation statements)

References 26 publications

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“…Another method for comet assessment is known as tail moment, that calculated as: measure of tail length by the measure of DNA in the tail, it was introduced by olive et al [15] The method chosen depends on the resources investigator and study design [16]. Results of this study agreed with Dridi et al, 2016 concluded, and showed a significant increase in DNA damage particularly in class 3 and 4 according to both treatment and dosing_time in MMF_treated rats [5].…”

Section: Resultssupporting

confidence: 76%

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The ability of Mycophenolate Mofetil to induce chromosome aberration and DNA damage in Mus Musculus Mice

NEAMA¹,

SADEQ²

2019

Tikrit J. Pure Sci.

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Mycophenolate mofetil (MMF, cellcept) is widely used in maintenance immunosuppressive therapy for prevention refractory rejection in sold organ transplant recipients. MMF is orally used, and rapidly metabolized to its active constituent Mycophenolic acid. MPA is an inhibitor of Inosine Monophosphate Dehydrogenase ΙΙ (IMPDH ΙΙ) in lymphocyte causing in reduction in intracellular guanine nucleotide pools and leads to inhibition of lymphocyte proliferation. MMF is considered to be an effective and safe immunosuppressive agent compared with other medicins. MMF lacks the nephrotoxicity. But it has important side effects, gastrointestinal and heamatological adverse effects are the most common. The results of this study show the high significant in total chromosome aberrations in treatment groups compared with control. Also there is high significant differences in total damage DNA in treatment groups than control. In conclusion, MMF may has a high genotoxicity by induced chromosome aberration and DNA damage.

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Section: Resultssupporting

confidence: 76%

“…Heamatological toxicity is among the side effects of MMF administration, and while anemia is the most commonly, due to bone marrow suppression or heamolysis, Leukopenia is the most important adverse effect. These are usually mild and doserelated [5]. Myelotoxicity may appears with MMF treatment [6].…”

Section: Introductionmentioning

confidence: 99%

The ability of Mycophenolate Mofetil to induce chromosome aberration and DNA damage in Mus Musculus Mice

NEAMA¹,

SADEQ²

2019

Tikrit J. Pure Sci.

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“…In this study, the entrainment was assessed by the circadian rhythmicity in rectal temperature, the acrophase (peak time) was used as a marker rhythm index and the rectal temperature was measured with a digital thermometer (OMRON Ecosmart, Holt55005) (Khedhaier et al 2003;Dridi et al 2013). …”

Section: Animals and Synchronizationmentioning

confidence: 99%

Circadian time-dependent hepatic and renal toxicities to valproic acid in mice

Ben-Cherif

Dridi

Haouas

et al. 2015

Biological Rhythm Research

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This study aims to investigate whether hepatic and renal valproic acid (VPA) toxicities varied according to the dosing time in the 24-h scale in mice. VPA was administered by i.p. route to different groups of animals at four different circadian stages (1, 7, 13, and 19 h after light onset (HALO)). Biochemical study and histopathological examinations on liver and kidney sections were performed. The results showed that the hepatic and renal toxicity induced by VPA was time related. Animals treated at 19 HALO showed vacuolar degenerative changes, congestions, and inflammatory areas on liver parenchyma. Lesions within proximal tubules were observed in the kidney in groups treated at 19 HALO. The largest increases in alanine aminotransferase, alkaline phosphatase and plasma creatinine activities were also observed at 19 HALO. The obtained data indicate that the optimal hepatic and renal tolerance is observed when VPA was injected in the middle of the light-rest span of mice. IntroductionCircadian rhythms are an inherent property of living systems and constitute an essential part of their internal and external temporal order. In mammals, daily rhythms in behavior and physiology are regulated by the circadian timing system, which includes the suprachiasmatic nuclei considered as one of the master biological clocks (Reinberg 1992;Liu et al. 1997). Several physiological and biochemical processes in laboratory animals and humans have been found to vary rhythmically over a 24-h period (i.e., to exhibit a circadian or diurnal rhythm) (Lemmer 1996). Temporal differences in drug action and toxicity have been recognized for over 50 years in humans and in laboratory animals. Many drugs vary in potency and/or toxicity associated with the rhythmicity of biochemical, physiological, and behavioral processes (Smolensky & D'alonzo 1993). Identification of rhythms in animal models leads to provide an optimal dosing time and suggests guidelines to a potential chronotherapy; indeed, the dosing of a medication at the proper biological time with reference to circadian rhythms can result in the modulation of its efficiency or its toxicity.

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Role of Pharmacokinetics in Chronotherapeutics

Wang

Chen

et al. 2020

Circadian Pharmacokinetics

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Circadian variation in haematological toxicity of the immunosuppressive agent "Mycophenolate Mofetil" in rats

Cited by 12 publications

References 26 publications

The ability of Mycophenolate Mofetil to induce chromosome aberration and DNA damage in Mus Musculus Mice

The ability of Mycophenolate Mofetil to induce chromosome aberration and DNA damage in Mus Musculus Mice

Circadian time-dependent hepatic and renal toxicities to valproic acid in mice

Role of Pharmacokinetics in Chronotherapeutics

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