Trimetazidine reduces early and long-term effects of experimental renal warm ischemia: A dose effect study

Cau, Jérôme; Favreau, Fréderic; Tillement, J P; Lerman, Lilach O.; Hauet, Thierry; Goujon, Jean Michel

doi:10.1016/j.jvs.2007.10.036

Cited by 27 publications

(35 citation statements)

References 41 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several papers have shown the protective effect of trimetazidine on kidney grafts from cold preservation and reperfusion (27,28) and against warm ischemia (12,15,16). Hauet et al (27) evaluated the renal function of isolated perfused pig kidneys after 48 hours of cold storage with Euro-Collins (EC) solution plus trimetazidine (EC+TMZ), standard EC solution, or University of Wisconsin (UW) solution.…”

Section: Discussionmentioning

confidence: 99%

“…The anti-anginal medication trimetazidine (TMZ) has been shown to protect the myocardium cells through inhibition of fatty acid oxidation and reciprocal activation of pyruvate oxidation, resulting in less production and accumulation of lactate and hydrogen cation, H+, during ischaemia (14). Experimental studies have also shown a protective effect in kidney I/R injury (15,16). Nevertheless, there has been no comparative study between renal hypothermia and trimetazidine in the protection of I/R injury.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Comparative study between trimetazidine and ice slush hypothermia in protection against renal ischemia/reperfusion injury in a porcine model

et al. 2011

View full text Add to dashboard Cite

Purpose: The aim of the study was to compare the effects of renal ice slush hypothermia and the use of trimetazidine in the protection against ischemia/reperfusion (I/R) injury. Materials and Methods: Fifteen farm pigs were submitted to left kidney ischemia and right nephrectomy during the same procedure. Animals were divided into three groups. Group 1 was submitted to warm ischemia; Group 2 was submitted to cold ischemia with ice slush; and Group 3 received trimetazidine 20 mg one day and 4 hours before surgery. Ischemia time was 120 minutes in all three groups. Serum creatinine (SCr) and plasma iohexol clearance (CLioh) were measured before surgery and on postoperative days (PODs) 1,3,7, and 14. Semi-quantitative analyses of histological alterations were performed by a pathologist. A p value of < 0.05 was considered significant. Results: All groups showed elevation of serum creatinine in the first week. Serum creatinine was higher in Group 3 in the first and third postoperative days (Mean Cr: 5.5 and 8.1 respectively). Group 2 showed a lower increase in creatinine and a lower decrease in iohexol clearance than the others. Renal function stabilized in the fourteenth POD in all three groups. Analyses of histological alterations did not reach statistical significance between groups. Conclusion: Trimetazidine did not show protection against renal I/R injury in comparison to warm ischemia or hypothermia in a porcine model submitted to 120 minutes of renal ischemia.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Comparative study between trimetazidine and ice slush hypothermia in protection against renal ischemia/reperfusion injury in a porcine model

et al. 2011

View full text Add to dashboard Cite

show abstract

“…The horizontal line at which the repair ends is much higher than the start, representing the decrease in function and a higher creatinine level. [27][28][29] which may represent an important advance in translating potential therapies to larger animals, including humans. Nephrotoxic models and ureteral obstruction models have also been described, again with fibrosis representing a primary end point, but we are not aware of sepsis models in which fibrosis has been evaluated.…”

Section: Question 1 How Do We Define Progression After Aki?mentioning

confidence: 99%

Progression after AKI

Basile

Bonventre

Mehta

et al. 2016

Journal of the American Society of Nephrology

367

298

View full text Add to dashboard Cite

Recent clinical studies indicate a strong link between AKI and progression of CKD. The increasing prevalence of AKI must compel the nephrology community to consider the long-term ramifications of this syndrome. Considerable gaps in knowledge exist regarding the connection between AKI and CKD. The 13th Acute Dialysis Quality Initiative meeting entitled "Therapeutic Targets of Human Acute Kidney Injury: Harmonizing Human and Experimental Animal Acute Kidney Injury" convened in April of 2014 and assigned a working group to focus on issues related to progression after AKI. This article provides a summary of the key conclusions and recommendations of the group, including an emphasis on terminology related to injury and repair processes for both clinical and preclinical studies, elucidation of pathophysiologic alterations of AKI, identification of potential treatment strategies, identification of patients predisposed to progression, and potential management strategies.

show abstract

“…9 Its anti-ischemic effects on the kidney have been experimentally assessed in various models including cell culture 10 isolated and perfused kidneys 11 and in vivo. 12,13 TMZ has different pharmacological properties that could be relevant for the prevention of organ damage from I/R by reduction of intracellular acidosis, 14 preservation of ATP production, limitation of inflammatory reaction, and thus of ROS generation. 15 However, the exact mechanism of action of TMZ on renal cells is not clear.…”

Section: Introductionmentioning

confidence: 99%

Effects of trimetazidine on the Akt/eNOS signaling pathway and oxidative stress in anin vivorat model of renal ischemia-reperfusion

et al. 2014

View full text Add to dashboard Cite

Renal ischemia reperfusion (I/R) injury, which occurs during renal surgery or transplantation, is the major cause of acute renal failure. Trimetazidine (TMZ), an anti-ischemic drug, protects kidney against the deleterious effects of I/R. However its protective mechanism remains unclear. The aim of this study is to examine the relevance of Akt, endothelial nitric oxide synthase (eNOS), and hypoxia inducible factor-1a (HIF-1a) on TMZ induced protection of kidneys against I/R injury. Wistar rats were subjected to 60 min of warm renal ischemia followed by 120 min of reperfusion, or to intraperitoneal injection of TMZ (3 mg/kg) 30 min before ischemia. In sham operated group renal pedicles were only dissected. Compared to I/R, TMZ treatment decreased lactate dehydrogenase (845 ± 13 vs. 1028 ± 30 U/L). In addition, creatinine clearance and sodium reabsorption rates reached 105 ± 12 versus 31 ± 11 mL/min/g kidney weight and 95 ± 1 versus 68 ± 5%, respectively. Besides, we noted a decrease in malondialdehyde concentration (0.33 ± 0.01 vs. 0.59 ± 0.03 nmol/mg of protein) and an increase in glutathione concentration (2.6 ± 0.2 vs. 0.93 ± 0.16 mg GSH/mg of protein), glutathione peroxidase (95 ± 4 vs. 61 ± 3 mg GSH/min/mg of protein), and superoxide dismutase (25 ± 3 vs. 11 ± 2 U/mg of protein) and catalase (91 ± 12 vs. 38 ± 9 mmol/min/mg of protein) activities. Parallely, we noted a significant increase in p-Akt, eNOS, nitrite and nitrate (18 ± 2 vs. 8 ± 0.1 pomL/mg of protein), HIF-1a (333 ± 48 vs. 177 ± 14 mg/mg of protein) and heme oxygenase-1 (HO-1) levels regarding I/R. TMZ treatment improves renal tolerance to warm I/R. Such protection implicates an activation of Akt/eNOS signaling pathway, HIF-1a stabilization and HO-1 activation.

show abstract

Trimetazidine reduces early and long-term effects of experimental renal warm ischemia: A dose effect study

Abstract: Collectively, these data suggest that TMZ made the warm ischemic kidneys more resistant to the deleterious impact of a single episode of IR and could have a role in preserving the ischemic kidney from long-term damage.

Cited by 27 publications

References 41 publications

Comparative study between trimetazidine and ice slush hypothermia in protection against renal ischemia/reperfusion injury in a porcine model

Comparative study between trimetazidine and ice slush hypothermia in protection against renal ischemia/reperfusion injury in a porcine model

Progression after AKI

Effects of trimetazidine on the Akt/eNOS signaling pathway and oxidative stress in anin vivorat model of renal ischemia-reperfusion

Contact Info

Product

Resources

About