Protective Roles of Polyethylene Glycol and Trimetazidine against Cold Ischemia and Reperfusion Injuries of Pig Kidney Graft

Fauré, J.; Petit, Isabelle; Zhang, Keqiang; Dutheil, Delphine; Doucet, Christelle; Favreau, Fréderic; Eugène, Michel; Goujon, Jean Michel; Tillement, J P; Mauco, Gérard; Vandewalle, Alain; Hauet, Thierry

doi:10.1111/j.1600-6143.2004.00365.x

Cited by 42 publications

(27 citation statements)

References 34 publications

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“…Myeloid and lymphoid cell numbers increased both in the subglottis and trachea (data not shown for the trachea) while decreases were observed in the supraglottis. In other systems, increases in cell numbers are associated with histological and/or functional injury [27,28], suggesting that the supraglottis may have been less affected by the insults applied here. However, this does not explain the observation that cell numbers actually decreased in the supraglottis, suggesting active mobilization from the site.…”

Section: Discussionmentioning

confidence: 99%

Early immunological changes associated with laryngeal transplantation in a major histocompatibility complex-matched pig model

Barker

Murison

Macchiarini

et al. 2006

Clinical and Experimental Immunology

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SummaryLaryngeal transplantation is an increasingly viable proposition for patients with irreversible diseases of the larynx. One human transplant has been performed successfully, but many questions remain before routine transplantation can begin. In order to measure the immunological changes in mismatched transplants, it is first necessary to know the immediate combined effects of ischaemia-reperfusion injury (IRI) plus the added insult of major surgery in a fully matched setting. We measured the changes in immunologically active mucosal cells following 3 h of cold ischaemia and 8 h of in situ reperfusion in a major histocompatibility complex (MHC)-matched minipig model (n = 4). Biopsies were prepared for quantitative, multiple-colour immunofluorescence histology. The number of immunologically active cells was significantly altered above (supraglottis) and below (subglottis) the vocal cords following transplantation and reperfusion (P < 0·05, P < 0·001, respectively). However, the direction of the change differed between the two subsites: cell numbers decreased post-transplant in the supraglottis and increased in the subglottis. Despite the statistical evidence for IRI, these changes were less than the large normal inter-and intrapig variation in cell counts. Therefore, the significance of IRI in exacerbating loss of function or rejection of a laryngeal allograft is open to question. Longer-term studies are required.

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Section: Discussionmentioning

confidence: 99%

Early immunological changes associated with laryngeal transplantation in a major histocompatibility complex-matched pig model

Barker

Murison

Macchiarini

et al. 2006

Clinical and Experimental Immunology

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“…In this context, the antioxidant role of TMZ in the renal I/R injury has been investigated by administering it in vivo or by adding it to preservation solutions used for kidney transplantation [5,[10][11][12] . In addition, it has been suggested that TMZ can prevent the injury of the kidney as a remote organ by diminishing systemic oxidative stress in the body in the situations of I/R elsewhere [13] .…”

Section: Effectiveness Of Trimetazidine In Testicular Torsionmentioning

confidence: 99%

Protective Effects of Trimetazidine on Testicular Ischemia-Reperfusion Injury in Rats

Unal

Karataş

Savaş³

et al. 2007

Urol Int

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Introduction: We tried to prove the effectiveness of trimetazidine (TMZ) on testicular torsion-detorsion injury. Materials and Methods: 15 male rats were equally divided into three groups: group 1 was the sham-operated control group; group 2 had 2 h of unilateral testicular ischemia followed by 3 days of reperfusion, and group 3 had 2 h of unilateral testicular ischemia followed by 3 days of oral TMZ treatment (5 mg/kg, bid) during reperfusion. In the removed testicles, tissue reduced glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), malondialdehyde (MDA) levels and pathological modified Johnson scores (MJS) were evaluated. Mann-Whitney U test was used for statistical evaluations. Results: In group 2, on the ipsilateral side, GSH were significantly lower and MDA were higher than in groups 1 and 3, though GSH and MDA were not statistically different between groups 1 and 3. On the other hand, GPx in the control testicles of group 3 was significantly lower compared to those in the counterparts of both groups 1 and 2. Among three groups, GR determined in both testicles were not statistically different. On the ipsilateral side, MJS in group 3 were lower than in the sham group, but significantly higher than in group 2. Conclusions: According to this study, TMZ has an antioxidant effect on testicular torsion-detorsion injury, though the protective effect of TMZ seems to decrease in control testicles. Consequently it has been considered that TMZ can be only used in torsion patients with a healthy contralateral testicle after further studies have been conducted.

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“…Moreover, the vascular endothelium is also a key site of injury from ROS and endothelial cell dysfunction is central to the pathogenesis of chronic allograft nephropathy (2,3). We have previously evidenced the protective effect of TMZ on kidney grafts from cold preservation and reperfusion, showing that TMZ was efficient when added to various currently used preservation solutions (11,12). Several reports have described different pharmacological effects of TMZ which are relevant in the prevention of organ damage from IRI: partial inhibition of fatty acid ␤-oxidation (20), reduction of ionic imbalance during ischemia-reperfusion (I/R) (9), increase in phospholipid uptake turnover (33), and membrane protection against reoxygenation-induced stress (32,28).…”

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Comparison of protective effects of trimetazidine against experimental warm ischemia of different durations: early and long-term effects in a pig kidney model

Jayle¹,

Favreau²,

Zhang³

et al. 2007

American Journal of Physiology-Renal Physiology

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Acute renal failure (ARF) is often the consequence of an ischemia-reperfusion injury (IRI) and associated with high mortality. Warm ischemia (WI) is a crucial factor of tissue damage, and tissue destruction led by ischemia-reperfusion (I/R) can impact the early and long-term functional outcome. Trimetazidine (TMZ) is an anti-ischemic drug. Previously, we already verified its protective effect on a cold-ischemic pig kidney model by directly adding TMZ into the preservation solution (Faure JP, Baumert H, Han Z, Goujon JM, Favreau F, Dutheil D, Petit I, Barriere M, Tallineau C, Tillement JP, Carretier M, Mauco G, Papadopoulos V, Hauet T. Biochem Pharmacol 66: 2241–2250, 2003; Faure JP, Petit I, Zhang K, Dutheil D, Doucet C, Favreau F, Eugene M, Goujon JM, Tillement JP, Mauco G, Vandewalle A, Hauet T. Am J Transplant 4: 495–504, 2004). In this study, we aimed to study the potential effect of TMZ pretreatment (5 mg/kg iv 24 h before WI) on the injury caused by WI for 45, 60, and 90 min and reperfusion in a WI pig kidney model. Compared with sham-operated (control) and uninephrectomized animals (UNX), TMZ pretreatment significantly reduced deleterious effects after 45 min, and particularly 60 and 90 min, of WI by improving the recovery of renal function and minimizing the inflammatory response commonly prevalent in ischemic kidney injury. Compared with controls (control group and UNX group), it was observed that 1) hypoxia-inducible factor-1 (HIF-1α) expression occurred earlier and with a higher intensity in the TMZ-treated groups; 2) the reduction of IRI during the first week following reperfusion was correlated with an earlier and greater expression of stathmin, which is involved in the process of tubular repair; and 3) the tubulointerstitial fibrosis was reduced, particularly after 60 and 90 min of WI. In conclusion, TMZ made the warm-ischemic kidneys more resistant to the deleterious impact of a single episode of I/R and reduced early and long-term subsequent damage.

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Protective Roles of Polyethylene Glycol and Trimetazidine against Cold Ischemia and Reperfusion Injuries of Pig Kidney Graft

Abstract: Ischemia-reperfusion injury (IRI) represents an alloindependent risk factor which favors chronic allograft nephropathy (CAN).

Cited by 42 publications

References 34 publications

Early immunological changes associated with laryngeal transplantation in a major histocompatibility complex-matched pig model

Early immunological changes associated with laryngeal transplantation in a major histocompatibility complex-matched pig model

Protective Effects of Trimetazidine on Testicular Ischemia-Reperfusion Injury in Rats

Comparison of protective effects of trimetazidine against experimental warm ischemia of different durations: early and long-term effects in a pig kidney model

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