Studies on the Immunosuppressive Properties of Cyclosporin a in Rats Receiving Renal Allografts

Homan, William P.; Fabre, John W.; Williams, Keryn A.; Millard, P.R.; Morris, Peter J.

doi:10.1097/00007890-198005000-00003

Cited by 90 publications

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“…Further refinement of this model will require a dose titration study to determine drug serum levels among animals with the goal of achieving "ideal doses." Although a combination of three agents was employed here, there is evidence to suggest that immunosuppressants are effective when administered separately by the oral route 3,4 . On the other hand, Einsinger 5 observed that cyclosporin did not delay cutaneous and fascial muscle healing in rats.…”

Section: Discussionmentioning

confidence: 99%

An experimental model for the study of drug effects on cutaneous healing

Júnior¹,

Rodrigues²,

Delfino³

2007

Acta Cir. Bras.

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Purpose:Immunosuppressive agents are known to interfere with the healing of surgical wounds. The increasing use of these drugs warrants a better understanding of their effects on wound healing. The aim of this study was to develop an experimental model that would allow for a reliable and rapid assessment of drug effects on cutaneous wound healing. Methods: Thirty syngeneic Lewis rats underwent surgical incision on their dorsal region, in the presence or absence of a three-week regimen of immunosuppressant drug therapy (i.e., cyclosporin, azathioprine, and prednisone). Surgical site tissue was collected at intervals over 21 days after surgery and analyzed for cell number and collagen fiber content. Both of these quantitative assessments were performed using digital image capture with the Image Pro Plus 4.5 software. Results: Computerized histomorphometric analyses revealed an apparent inhibition of cellular responses and collagen fiber production in drug-treated animals compared to control animals. Conclusion: The experimental model was reproducible, easy to perform, and allowed for quantitative histological evaluations. It may be useful for the study of surgical healing in the presence of other drug classes. Key words: Animal Experimentation. Immunosuppression. Wound Healing. Rats. RESUMOObjetivo: Várias drogas podem interferir no processo de cicatrização de feridas cirúrgicas, incluindo-se aqui agentes imunossupressores. Devido ao crescimento do número de pessoas tratadas com estas drogas, um modelo experimental, baseado em um sistema computadorizado de avaliação histológica, para verificar os efeitos destas drogas sobre a cicatrização cirúrgica pode se mostrar útil e permitir, também, o estudo das ações de outras drogas sobre este processo. Métodos: Trinta ratos Lewis isogênicos foram submetidos a incisões cirúrgicas na região dorsal e metade deles foi imunossuprimida utilizando-se ciclosporina, azatioprina e prednisona por 3 semanas. Em cinco intervalos de tempo pré-fixados, avaliações histológicas quantitativas de células e fibras colágenas dos sítios operatórios de animais tratados e controles foram realizadas, utilizando-se captura digital das imagens por meio do programa Image Pro Plus 4.5. Resultados: A avaliação dos sítios cirúrgicos mostrou, nos animais sob uso de drogas imuossupressoras, aparente diminuição no número de células e na produção de fibras colágenas. Conclusões: O modelo experimental proposto mostrou-se viável por exigir recursos pouco sofisticados, pela fácil realização e por fornecer avaliações histológicas quantitativas. Este modelo poderá ser utilizado para o estudo da ação de outras classes de drogas sobre a cicatrização cirúrgica.

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Section: Discussionmentioning

confidence: 99%

An experimental model for the study of drug effects on cutaneous healing

Júnior¹,

Rodrigues²,

Delfino³

2007

Acta Cir. Bras.

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“…After allogeneic kidney transplantation in recipients pretreated with donor strain blood, the histopathological findings in the allografts are consistent with chronic rejection [2]. Although the precise action of CsA is not completely known, the main effect of CsA is directed to the cellular mediated immune re sponse, probably due to a selective action on helper T lymphocytes [6,8,17,18]. Through these cells inhibition of B cell antibody production may occur as well.…”

Section: Discussionmentioning

confidence: 99%

“…Steroids, however, are hypertensiogenic themselves [4,5]. Recently, cyclosporin A (CsA) proved to be a powerful immunosuppressive [6], effective in experimen tal kidney transplantation [7][8][9] as well as in human transplantation [10]. To avoid the use of corticosteroids, CsA was used to improve immunosuppression in our allogeneic kidney transplantation model in rats.…”

Section: Introductionmentioning

confidence: 99%

Effect of Cyclosporin A on the Development of Posttransplantation Hypertension in Rat Renal Allograft Recipients

Keijzer¹,

Provoost²,

Aken³

et al. 1985

Nephron

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Hypertension secondary to renal transplantation was studied in our experimental model in the rat. In this model an intravenous injection of donor strain blood into recipients of allogeneic donor kidneys prior to transplantation was used to prolong the allograft survival. A reduced renal function associated with the hypertension was suggestive of incomplete prevention of the rejection process. We studied the effect of cyclosporin A, either alone or as adjuvant immunosuppressive therapy, on renal function and systolic blood pressure. Either way, cyclosporin A resulted in normotensive allograft recipients and in a better function of the graft when compared with recipients pretreated with donor strain blood only.

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“…* p < 0.05 as com pared with the value obtained in each control group. is necessary to prevent allograft rejection in rats [20), short-term CsA administration causes the suppression of DNA, RNA, and protein syntheses. These changes may well cause suppression of growth and regenera tive capabilities, as well as the decreases in amylase and lipase activities and in the num ber of muscarinic receptors.…”

Section: Discussionmentioning

confidence: 99%

Functional and Morphological Changes of the Exocrine Pancreas in Ciclosporin-Treated Rats

Hirakawa¹,

Ohkuma

Kuriyama

1991

Eur Surg Res

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We have examined whether or not ciclosporin A (CsA) affects structure and function of the exocrine pancreas. Male Wistar rats were treated once a day for 7 days with intraperitoneal injections of vehicle or 5, 15, 30, or 50 mg/kg of CsA. Following the CsA treatment, incorporations of [³H]thymidine into DNA and [³H]orotic acid into RNA were found to be significantly reduced in a dose-dependent manner up to 30 and 15 mg/kg, respectively, at which doses the incorporations reached a plateau. The incorporation of [³H]-L-leucine into protein also decreased by 36% at the dose of 5 and by 53% at the dose of 50 mg/kg of CsA. The activities of amylase and lipase in the pancreas also decreased in the CsA-treated rats. Furthermore, a significant reduction in the specific binding of [³H]N-methylscopolamine to muscarinic receptor was observed following the administration of CsA. The Scatchard analysis for the [³H]N-methylscopolamine binding to the pancreatic membrane revealed a significant decrease in B_max, but not in K_d values in the CsA-treated animals. In addition, it was found histologically that administration of CsA induced cellular atrophy, cytoplasmic vacuolization, and cellular necrosis in the exocrine pancreas. These results strongly suggest that prolonged treatment with CsA may induce the suppression of pancreatic exocrine functions by decreasing the contents of amylase and lipase as well as the number of muscarinic receptors, possibly by the inhibition of the syntheses of protein and DNA in the exocrine pancreas.

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Studies on the Immunosuppressive Properties of Cyclosporin a in Rats Receiving Renal Allografts

Cited by 90 publications

References 0 publications

An experimental model for the study of drug effects on cutaneous healing

An experimental model for the study of drug effects on cutaneous healing

Effect of Cyclosporin A on the Development of Posttransplantation Hypertension in Rat Renal Allograft Recipients

Functional and Morphological Changes of the Exocrine Pancreas in Ciclosporin-Treated Rats

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