Granisetron and carvedilol can protect experimental rats againstadjuvant-induced arthritis

Ahmed, Yasmin Moustafa; Messiha, Basim Anwar Shehata; Abo-Saif, Ali A.

doi:10.1080/08923973.2017.1286502

Cited by 20 publications

(18 citation statements)

References 78 publications

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“…(20) In addition, this compound was able to alleviate inflammatory arthritis. (43) Consistent with previous findings, our work further disclosed that granisetron also exhibited beneficial roles in sepsis-induced liver injury, which was linked to its anti-inflammatory effects. Macrophages were shown to be a target for granisetron in the present study.…”

Section: Discussionsupporting

confidence: 92%

“…For example, granisetron could decrease colonic levels of Tnf‐α, Il‐6, and myeloperoxidase activity to protect rats against an experimental model of inflammatory bowel disease . In addition, this compound was able to alleviate inflammatory arthritis . Consistent with previous findings, our work further disclosed that granisetron also exhibited beneficial roles in sepsis‐induced liver injury, which was linked to its anti‐inflammatory effects.…”

Section: Discussionsupporting

confidence: 89%

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Intestinal Microbiota Mediates the Susceptibility to Polymicrobial Sepsis‐Induced Liver Injury by Granisetron Generation in Mice

et al. 2019

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Sepsis‐induced liver injury is recognized as a key problem in intensive care units. The gut microbiota has been touted as an important mediator of liver disease development; however, the precise roles of gut microbiota in regulating sepsis‐induced liver injury are unknown. Here, we aimed to investigate the role of the gut microbiota in sepsis‐induced liver injury and the underlying mechanism. Cecal ligation and puncture (CLP) was used to induce polymicrobial sepsis and related liver injury. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota in these pathologies. Metabolomics analysis was performed to characterize the metabolic profile differences between sepsis‐resistant (Res; survived to 7 days after CLP) and sepsis‐sensitive (Sen; moribund before or approximately 24 hours after CLP) mice. Mice gavaged with feces from Sen mice displayed more‐severe liver damage than did mice gavaged with feces from Res mice. The gut microbial metabolic profile between Sen and Res mice was different. In particular, the microbiota from Res mice generated more granisetron, a 5‐hydroxytryptamine 3 (5‐HT3) receptor antagonist, than the microbiota from Sen mice. Granisetron protected mice against CLP‐induced death and liver injury. Moreover, proinflammatory cytokine expression by macrophages after lipopolysaccharide (LPS) challenge was markedly reduced in the presence of granisetron. Both treatment with granisetron and genetic knockdown of the 5‐HT3A receptor in cells suppressed nuclear factor kappa B (NF‐кB) transactivation and phosphorylated p38 (p‐p38) accumulation in macrophages. Gut microbial granisetron levels showed a significantly negative correlation with plasma alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels in septic patients. Conclusion: Our study indicated that gut microbiota plays a key role in the sensitization of sepsis‐induced liver injury and associates granisetron as a hepatoprotective compound during sepsis development.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 89%

Intestinal Microbiota Mediates the Susceptibility to Polymicrobial Sepsis‐Induced Liver Injury by Granisetron Generation in Mice

et al. 2019

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“…The receiver compartment was full of distilled water, 28 and the donor compartment contained a DH-TENV formulation (equivalent to 3 mg DH) or DH solution. The analysis was conducted at 37 ± 2°C with continuous stirring at 100 rpm for 24 h. At (1,2,3,4,5,6,8,12, and 24 h) time points, samples were removed, and the DH content was determined using a spectrophotometer at λ max of 292. After each withdrawal, the receiver compartment was refilled with fresh medium of equal quantity to preserve the sink condition.…”

Section: Ex Vivo Skin Permeation Analysismentioning

confidence: 99%

“…Serum anti-CCP, COMP, and IL-6 were subsequently assessed using ELISA kits according to the manufacturer guidelines based on principles described in previous studies. 2,41,42 Receptor activator of nuclear factor kappa-Β ligand (RANKL) tissue levels were measured using a previously described Western blot technique 43,44 using a Mini PROTEIN electrophoresis system (Bio-Rad). Briefly, a portion of the synovial tissue was exposed to radioimmunoprecipitation assay (RIPA) lysis buffer.…”

Section: In Vivo Analysis Of Optimized Dh-tenvs In Cfa-induced Ra In mentioning

confidence: 99%

“…1 Studies have shown that bias with RA is seen mainly in developed countries, with a prevalence of 1-2%, and it affects more women than men because of hormonal effects on immune cells. [2][3][4] RA is mostly associated with bone erosion, bone destruction, cartilage degradation, synovial inflammation, and joint rigidity. 5 Long-term RA therapy, including glucocorticoids, non-steroidal anti-inflammatory drugs, biological therapies, and disease-modifying anti-RA drugs such as methotrexate (MTX) and leflunomide, have detrimental effects on the kidneys, bones, stomach, and other organs.…”

Section: Introductionmentioning

confidence: 99%

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<p>Mitigation of Rheumatic Arthritis in a Rat Model via Transdermal Delivery of Dapoxetine HCl Amalgamated as a Nanoplatform: In vitro and in vivo Assessment</p>

Salem¹,

Nafady²,

Kharshoum³

et al. 2020

IJN

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Purpose: Dapoxetine HCl (DH), a selective serotonin reuptake inhibitor, may be useful for the treatment of rheumatic arthritis (RA). The purpose of this study was to investigate the therapeutic efficacy of transdermal delivery of DH in transethosome nanovesicles (TENVs). This novel delivery of DH may overcome the drawbacks associated with orally administered DH and improve patient compliance. Methods: DH-TENV formulations were prepared using an injection-sonication method and optimized using a 3 3 Box-Behnken-design with Design Expert ® software. The TENV formulations were assessed for entrapment efficiency (EE-%), vesicle size, zeta potential, in vitro DH release, and skin permeation. The tolerability of the optimized DH-TENV gel was investigated using a rat skin irritation test. A pharmacokinetic analysis of the optimized DH-TENV gel was also conducted in rats. Moreover, the anti-RA activity of the optimized DH-TENV gel was assessed based on the RAspecific marker anti-cyclic cirtullinated peptide antibody (anti-CCP), the cartilage destruction marker cartilage oligomeric matrix protein (COMP) and the inflammatory marker interleukin-6 (IL-6). Level of tissue receptor activator of nuclear factor kappa-Β ligand (RANKL) were also assessed. Results: The optimized DH-TENV formulation involved spherical nanovesicles that had an appropriate EE-% and skin permeation characteristic. The DH-TENV gel was well tolerated by rats. The pharmacokinetics analysis showed that the optimized DH-TENV gel boosted the bioavailability of the DH by 2.42-and 4.16-fold compared to the oral DH solution and the control DH gel, respectively. Moreover, it significantly reduced the serum anti-CCP, COMP and IL-6 levels and decreased the RANKL levels. Furthermore, the DH-TENV gel attenuated histopathological changes by almost normalizing the articular surface and synovial fluid. Conclusion:The results indicate that DH-TENVs can improve transdermal delivery of DH and thereby alleviate RA.

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Immunostimulant, hepatoprotective, and nephroprotective potential of Bacillus subtilis (NMCC-path-14) in comparison to dexamethasone in alleviating CFA-induced arthritis

Mazhar,

Naz,

Zulfiqar

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

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Granisetron and carvedilol can protect experimental rats againstadjuvant-induced arthritis

Abstract: Serotonin 5-HT receptor blockers and adrenergic receptor blockers, represented by granisetron and carvedilol, may represent new promising protective strategies against RA, at least owing to immune-modulator, anti-inflammatory and antioxidant potentials.

Cited by 20 publications

References 78 publications

Intestinal Microbiota Mediates the Susceptibility to Polymicrobial Sepsis‐Induced Liver Injury by Granisetron Generation in Mice

Intestinal Microbiota Mediates the Susceptibility to Polymicrobial Sepsis‐Induced Liver Injury by Granisetron Generation in Mice

<p>Mitigation of Rheumatic Arthritis in a Rat Model via Transdermal Delivery of Dapoxetine HCl Amalgamated as a Nanoplatform: In vitro and in vivo Assessment</p>

Immunostimulant, hepatoprotective, and nephroprotective potential of Bacillus subtilis (NMCC-path-14) in comparison to dexamethasone in alleviating CFA-induced arthritis

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