Paroxetine and rivastigmine mitigates adjuvant-induced rheumatoid arthritis in rats: Impact on oxidative stress, apoptosis and RANKL/OPG signals

Shafiey, Sara I.; Mohamed, Wafaa R.; Abo-Saif, Ali A.

doi:10.1016/j.lfs.2018.09.046

Cited by 30 publications

(32 citation statements)

References 59 publications

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“…Administration of DH-TENV gel to RA rats significantly (P < 0.05) decreased tissue RANKL expression compared to the untreated RA group, with a significantly greater decrease compared to MTX, DH gel, or oral DH ( Figure 6). These data agree with a previous study 40 that showed that the SSRI paroxetine had an anti-RA effect on CFA-induced RA by modulating RANKL expression.…”

Section: Pharmacokinetic Analysis Of the Optimized Dh-tenvsupporting

confidence: 93%

“…The rats were divided into seven groups (eight rats per group) as follows: normal control group (rats received normal saline), DH-TENV gel group (rats received 1 g/day optimized DH-TENV gel), RA group (rats received 0.4 mL/limb/3 day subcutaneous CFA for RA induction; 38 ), MTX+RA group (rats received CFA as in the RA group and 0.1 mg/kg/day oral methotrexate), 39 DH-TENV gel+RA group (rats received CFA as in the RA group and 1 g/day optimized DH-TENV gel), DH gel+RA group (rats received CFA as in the RA group and 1 g/day DH gel), and oral DH+RA group (rats received CFA as in the RA group and 10 mg/kg/day oral DH solution). 40 To induce RA, 0.4 mL CFA was subcutaneously injected into the planter surface of the hind limbs on days 1 (right hind limb), 4 (left hind limb), and 7 (right hind limb), with a 3-day interval between each dose. 38 The gel was applied on the dorsal surface of each rat to a 4-cm 2 shaved area.…”

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

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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Section: Pharmacokinetic Analysis Of the Optimized Dh-tenvsupporting

confidence: 93%

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

confidence: 99%

<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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“…Model Group II was characterized by high expression of caspase-3, as evidenced by intensive brown coloring (Figure 8b). In agreement with the recently obtained results of Shafiey et al [57] and Abdel-Maged et al [58], it is logically explained that apoptosis may be one of the mechanisms of progression of rheumatoid arthritis due to the activation of proapoptotic proteins like caspase-3.…”

Section: Immunohistochemistry Analysissupporting

confidence: 90%

“…The immunohistochemical study of caspase-3 was conducted following the method described by Shafiey et al [57] in some modification. Briefly, dewaxing and rehydration of ankle slices were performed, followed by buffer washing and heating in a water bath at 95°C for one hour.…”

Section: Immunohistochemistry Analysis Of Caspase-3 Expression Levelsmentioning

confidence: 99%

Anti-Arthritic Effect of Chicken Embryo Tissue Hydrolyzate Against Adjuvant Arthritis in Rats (X-Ray Microtomographic and Histopathological Analysis)

Rzhepakovsky¹,

Avanesyan²,

Benlidayı³

et al. 2020

Preprint

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Finding new, safe strategies to prevent and control rheumatoid arthritis is an urgent task. Of particular interest in this regard are bioactive peptides and peptide-rich protein hydrolyzates, which represent a new trend in the development of functional foods and nutraceuticals. The resulting tissue hydrolyzate of the chicken embryo (CETH) has been evaluated for acute toxicity and tested against chronic arthritis induced by Freund's full adjuvant in rats. The anti-arthritic effect of CETH was studied on the 28th day of the experiment after two weeks of oral administration of CETH at doses of 60 and 120 mg/kg body weight. Arthritis was evaluated on the last day of the experiment on the injected animal paw using X-ray computerized microtomography and histopathology analysis methods. The CETH effect was compared with the non-steroidal anti-inflammatory drug diclofenac sodium (5 mg/kg). Oral administration of CETH was accompanied by effective dose-dependent correction of morphological changes caused by the adjuvant injection. CETH had relatively high recovery effects in terms of parameters for reducing inflammatory edema, inhibition of osteolysis, prevention of osteophitosis, reduction of the inflammatory reaction of periarticular tissues, and cartilage degeneration. This study presents a potential theoretical strategy for the safe correction of this pathological process and, for the first time, shows that CETH may be a powerful potential nutraceutical agent or bioactive component of functional products in the treatment of rheumatoid arthritis.

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“…CES-1 may play important role in pharmacokinetics and pharmacodynamics of some anti-inflammatory drugs (Mishima et al, 1991), but CES-1 also has not been reported as a therapeutic target for RA. Recently rivastigmine, a known AChE inhibitor, was reported to have therapeutic effects in a complete Freund's adjuvant-induced model of arthritis (Shafiey et al, 2018). Furthermore, it was found that AChE activity was increased with age and may increase RA risk and severity in elderly people (Sato et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effects of Tryptanthrin and Tryptanthrin-6-Oxime in Models of Rheumatoid Arthritis

et al. 2020

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Rheumatoid arthritis (RA) is a chronic autoimmune disease involving joint and bone damage that is mediated in part by proteases and cytokines produced by synovial macrophages and fibroblast-like synoviocytes (FLS). Although current biological therapeutic strategies for RA have been effective in many cases, new classes of therapeutics are needed. We investigated anti-inflammatory properties of the natural alkaloid tryptanthrin (TRYP) and its synthetic derivative tryptanthrin-6-oxime (TRYP-Ox). Both TRYP and TRYP-Ox inhibited matrix metalloproteinase (MMP)-3 gene expression in interleukin (IL)-1b-stimulated primary human FLS, as well as IL-1b-induced secretion of MMP-1/3 by FLS and synovial SW982 cells and IL-6 by FLS, SW982 cells, human umbilical vein endothelial cells (HUVECs), and monocytic THP-1 cells, although TRYP-Ox was generally more effective and had no cytotoxicity in vitro. Evaluation of the therapeutic potential of TRYP and TRYP-Ox in vivo in murine arthritis models showed that both compounds significantly attenuated the development of collagen-induced arthritis (CIA) and collagen-antibody-induced arthritis (CAIA), with comparable efficacy. Collagen II (CII)specific antibody levels were similarly reduced in TRYP-and TRYP-Ox-treated CIA mice. TRYP and TRYP-Ox also suppressed proinflammatory cytokine production by lymph node cells from CIA mice, with TRYP-Ox being more effective in inhibiting IL-17A, granulocyte-macrophage colony-stimulating factor (GM-CSF), and receptor activator of nuclear factor-kB ligand (RANKL). Thus, even though TRYP-Ox generally had a better in vitro profile, possibly due to its ability to inhibit c-Jun N-terminal kinase (JNK), both TRYP and TRYP-Ox were equally effective in inhibiting the clinical symptoms and damage associated with RA. Overall, TRYP and/or TRYP-Ox may represent potential new directions for the pursuit of novel treatments for RA.

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Paroxetine and rivastigmine mitigates adjuvant-induced rheumatoid arthritis in rats: Impact on oxidative stress, apoptosis and RANKL/OPG signals

Cited by 30 publications

References 59 publications

<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>

<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>

Anti-Arthritic Effect of Chicken Embryo Tissue Hydrolyzate Against Adjuvant Arthritis in Rats (X-Ray Microtomographic and Histopathological Analysis)

Therapeutic Effects of Tryptanthrin and Tryptanthrin-6-Oxime in Models of Rheumatoid Arthritis

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