The evaluate and compare the effects of the Tacrolimus and Sirolimus on the intestinal system using an intestinal cell culture model

Ferjani, H.; Abassi, Haila; Salem, Intidhar Ben; Guedri, Y.; Abid, Salwa; Achour, Abedallatif; Bacha, Hassen

doi:10.3109/15376516.2015.1090514

Cited by 4 publications

(4 citation statements)

References 49 publications

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“…However, in the ileum, SRL induced more pathological changes than SRL NCs (e.g., intestinal epithelial inflammatory cell infiltration, congestion, and increased glandular lymphoid follicles) (Figure ). There are some reports that SRL has strong toxicity. , But in the SRL NCs group, there was less direct contact of free drugs with the intestinal mucosa, which explains the lower toxicity . Overall, SRL NCs induced less toxicity and irritation compared with SRL.…”

Section: Results and Discussionmentioning

confidence: 87%

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Enhanced Bioavailability by Orally Administered Sirolimus Nanocrystals

Kong

Ji³

et al. 2019

ACS Appl. Bio Mater.

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Nanocrystallization can improve the dissolvability of insoluble medicines in water, making them easier to administer. In the present study, sirolimus (SRL) was nanocrystallized, and the transport mechanism and efficacy of both formulations were compared in vitro and in vivo. The results showed that the 120 nm sirolimus nanocrystals (SRL NCs) had better ability to pass through the Caco-2 cell monolayer. SRL NCs were uptaken by Caco-2 cells via multiple endocytosis pathways, and the endoplasmic reticulum (ER), Golgi apparatus, and microtubules were identified as vital organelles for expelling SRL NCs out of the cells. SRL NCs decreased CD4 + /CD8 + in normal mice after 14 days of daily gavage administration. Furthermore, SRL NCs enhanced the immune tolerance in an ovalbumin (OVA)-sensitized mouse model. SRL NCs significantly increased the percentage of Tregs (CD25 + Foxp3 + ) among CD4 + T cells. Collectively, these findings demonstrate that nanocrystallization of SRL enhances oral bioavailability, transcytosis, and prolongs drug residence time in vivo, while also enhancing SRL efficacy.

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Section: Results and Discussionmentioning

confidence: 87%

“…There are some reports that SRL has strong toxicity. 49,50 But in the SRL NCs group, there was less direct contact of free drugs with the intestinal mucosa, which explains the lower toxicity. 29 Overall, SRL NCs induced less toxicity and irritation compared with SRL.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Enhanced Bioavailability by Orally Administered Sirolimus Nanocrystals

Kong

Ji³

et al. 2019

ACS Appl. Bio Mater.

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“…Mycophenolate may enhance gut permeability, potentially providing a mechanism for its positive association with TMAO. Furthermore, sirolimus may alter intestinal microbiota composition, induce abnormalities in intestinal barrier function, and cause an increase in circulating proinflammatory cytokines [ 41 , 42 , 43 ]. In humans, sirolimus is metabolized in the intestinal wall and liver, returning from the small intestine to the gut lumen via counter-transport by enterocytes, and can induce mild gastrointestinal side effects [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Circulating Trimethylamine-N-Oxide Is Elevated in Liver Transplant Recipients

Trillos-Almanza,

Chvatal-Medina,

Connelly

et al. 2024

IJMS

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Liver transplant recipients (LTRs) have lower long-term survival rates compared with the general population. This underscores the necessity for developing biomarkers to assess post-transplantation mortality. Here we compared plasma trimethylamine-N-oxide (TMAO) levels with those in the general population, investigated its determinants, and interrogated its association with all-cause mortality in stable LTRs. Plasma TMAO was measured in 367 stable LTRs from the TransplantLines cohort (NCT03272841) and in 4837 participants from the population-based PREVEND cohort. TMAO levels were 35% higher in LTRs compared with PREVEND participants (4.3 vs. 3.2 µmol/L, p < 0.001). Specifically, TMAO was elevated in LTRs with metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, and polycystic liver disease as underlying etiology (p < 0.001 for each). Among LTRs, TMAO levels were independently associated with eGFR (std. β = −0.43, p < 0.001) and iron supplementation (std. β = 0.13, p = 0.008), and were associated with mortality (29 deaths during 8.6 years follow-up; log-rank test p = 0.017; hazard ratio of highest vs. lowest tertile 4.14, p = 0.007). In conclusion, plasma TMAO is likely elevated in stable LTRs, with impaired eGFR and iron supplementation as potential contributory factors. Our preliminary findings raise the possibility that plasma TMAO could contribute to increased mortality risk in such patients, but this need to be validated through a series of rigorous and methodical studies.

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“…Intestinal permeability is characterized by a loss of the gut epithelial wall integrity allowing different sizes of compounds to enter the systemic circulation (food antigens, commensal or pathogens bacteria, and their metabolites) ( 50 ). By using an intestinal epithelial cell line, Qasim et al have demonstrated the potential of mycophenolic acid to alter tight junction proteins expression and distribution and induce intestinal permeability that may be responsible for gastrointestinal adverse effects observed in transplant patients ( 51 ). This intestinal permeability could also have deleterious consequences such as chronic systemic inflammation ( 52 ).…”

Section: Alterations Of Gut Homeostasis In Solid Organ Transplantationmentioning

confidence: 99%

Is Intestinal Dysbiosis-Associated With Immunosuppressive Therapy a Key Factor in the Pathophysiology of Post-Transplant Diabetes Mellitus?

Faucher

Jardou²,

Brossier³

et al. 2022

Front. Endocrinol.

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Post-transplant diabetes mellitus (PTDM) is one of the most common and deleterious comorbidities after solid organ transplantation (SOT). Its incidence varies depending on the organs transplanted and can affect up to 40% of patients. Current research indicates that PTDM shares several common features with type 2 diabetes mellitus (T2DM) in non-transplant populations. However, the pathophysiology of PTDM is still poorly characterized. Therefore, ways should be sought to improve its diagnosis and therapeutic management. A clear correlation has been made between PTDM and the use of immunosuppressants. Moreover, immunosuppressants are known to induce gut microbiota alterations, also called intestinal dysbiosis. Whereas the role of intestinal dysbiosis in the development of T2DM has been well documented, little is known about its impacts on PTDM. Functional alterations associated with intestinal dysbiosis, especially defects in pathways generating physiologically active bacterial metabolites (e.g., short-chain fatty acids, trimethylamine N-oxide, indole and kynurenine) are known to favour several metabolic disorders. This publication aims at discussing the potential role of intestinal dysbiosis and dysregulation of bacterial metabolites associated with immunosuppressive therapy in the occurrence of PTDM.

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The evaluate and compare the effects of the Tacrolimus and Sirolimus on the intestinal system using an intestinal cell culture model

Cited by 4 publications

References 49 publications

Enhanced Bioavailability by Orally Administered Sirolimus Nanocrystals

Enhanced Bioavailability by Orally Administered Sirolimus Nanocrystals

Circulating Trimethylamine-N-Oxide Is Elevated in Liver Transplant Recipients

Is Intestinal Dysbiosis-Associated With Immunosuppressive Therapy a Key Factor in the Pathophysiology of Post-Transplant Diabetes Mellitus?

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