Nephrotoxicity studies of the immunosuppressants tacrolimus (FK506) and ascomycin in rat models

Mollison, Karl W.; Fey, Thomas A.; Krause, R. A.; Andrews, Janet M; Bretheim, Pat T.; Cusick, Patrick K.; Hsieh, Gin C.; Luly, Jay R.

doi:10.1016/s0300-483x(97)00167-4

Cited by 18 publications

(14 citation statements)

References 17 publications

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“…This may be due to the difference in serum concentration of tacrolimus following injection. Recent studies showed that tacrolimus concentration in blood increased gradually over the first 2 h and was maintained for at least 6 h following s.c. administration of tacrolimus in rats, however the concentration was much lower than that following an intraperitoneal administered dose (15).…”

Section: Discussionmentioning

confidence: 71%

Effect of Co-administration of Tacrolimus on the Pharmacokinetics of Multiple Subcutaneous Administered Interferon-Alpha in Rats

et al. 2009

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Section: Discussionmentioning

confidence: 71%

Effect of Co-administration of Tacrolimus on the Pharmacokinetics of Multiple Subcutaneous Administered Interferon-Alpha in Rats

et al. 2009

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“…Higher doses of CsA and tacrolimus might be feasible, although there was histologic evidence of kidney damage even at the doses used in this experiment. Continuous rather than pulsed administration might reduce the toxicity of these agents [33]. In this regard, we had considered several options following the preliminary experiment but decided against them for various reasons.…”

Section: Discussionmentioning

confidence: 99%

Tacrolimus and Cyclosporine A Are of No Benefit to Young Rats with Kaolin-Induced Hydrocephalus

2003

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Hydrocephalus causes damage to periventricular axons. Tacrolimus, cyclosporine A (CsA) and calpain inhibitors have been shown to protect axons in rat models of acute traumatic brain injury. We hypothesized that these agents would ameliorate the axon damage and behavioral effects in experimental hydrocephalus. Hydrocephalus was induced in 3-week-old rats by injection of kaolin into the cisterna magna. Tests of cognitive and motor function were performed on a weekly basis. In a blinded and randomized manner, tacrolimus (FK506; 3.6 mg/kg body weight) or CsA (10 mg/kg) was administered once daily by subcutaneous injection for 2 weeks, beginning 2 weeks after induction of hydrocephalus. In a separate experiment, calpain inhibitor I (10 mg/kg/day) was administered by continuous subcutaneous infusion. The brains were subjected to histopathological and biochemical analyses after 2 weeks of treatment. There was no statistically significant protection in regard to behavior, brain structure or brain composition in any of the experiments. However, there was biochemical and histological evidence of renal injury following chronic tacrolimus and CsA administration. Calcineurin inhibition does not offer significant protection in this rat model of hydrocephalus.

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“…Most studies including those detailed in the current review utilize calcineurin inhibitors such as tacrolimus (FK506) or Cyclosporine-A to suppress the immune system and permit hNSC engraftment. Unfortunately, we and others have found that these paradigms achieve only partial <30% engraftment of transplanted cells and can also lead to considerable toxicity when administered chronically (Ager et al, 2015, Anderson et al, 2011, Mollison et al, 1998). In several animal models of neurodegeneration including models of AD, PD, and HD these compounds have also been shown to modulate important aspects of disease pathology, greatly complicating interpretation (Cavallucci et al, 2013, Hong et al, 2010, Kitamura et al, 1994, Rozkalne et al, 2011, Yoshiyama et al, 2007).…”

Section: Remaining Challengesmentioning

confidence: 94%

Neural stem cell therapy for neurodegenerative disorders: The role of neurotrophic support

Marsh

Blurton‐Jones

2017

Neurochemistry International

153

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Neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease currently affect tens of millions of people worldwide. Unfortunately, as the world’s population ages, the incidence of many of these diseases will continue to rise and is expected to more than double by 2050. Despite significant research and a growing understanding of disease pathogenesis, only a handful of therapies are currently available and all of them provide only transient benefits. Thus, there is an urgent need to develop novel disease-modifying therapies to prevent the development or slow the progression of these debilitating disorders. A growing number of pre-clinical studies have suggested that transplantation of neural stem cells (NSCs) could offer a promising new therapeutic approach for neurodegeneration. While much of the initial excitement about this strategy focused on the use of NSCs to replace degenerating neurons, more recent studies have implicated NSC-mediated changes in neurotrophins as a major mechanism of therapeutic efficacy. In this mini-review we will discuss recent work that examines the ability of NSCs to provide trophic support to disease-effected neuronal populations and synapses in models of neurodegeneration. We will then also discuss some of key challenges that remain before NSC-based therapies for neurodegenerative diseases can be translated toward potential clinical testing.

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Nephrotoxicity studies of the immunosuppressants tacrolimus (FK506) and ascomycin in rat models

Cited by 18 publications

References 17 publications

Effect of Co-administration of Tacrolimus on the Pharmacokinetics of Multiple Subcutaneous Administered Interferon-Alpha in Rats

Effect of Co-administration of Tacrolimus on the Pharmacokinetics of Multiple Subcutaneous Administered Interferon-Alpha in Rats

Tacrolimus and Cyclosporine A Are of No Benefit to Young Rats with Kaolin-Induced Hydrocephalus

Neural stem cell therapy for neurodegenerative disorders: The role of neurotrophic support

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