Pharmacological Manipulation of Acute Cyclosporin Ischemic Renal Injury with Trimetazidine

Abstract

Cyclosporin has had a major impact on organ transplantation, but associated nephrotoxicity is a significant problem. Renal hypothermia, a known anti-ischemic maneuver, limits cyclosporin-ischemic renal failure. Pharmacological manipulation with an anti-ischemic agent, such as trimetazidine, may prevent cyclosporin nephrotoxicity. We tested this hypothesis in a canine single kidney model of cyclosporin-enhanced ischemic renal failure. Trimetazidine treatment was associated with significantly better biochemical and histological markers of renal function and structure. Trimetazidine may have a role to play in protecting against cyclosporin nephrotoxicity in clinical renal transplantation.

Cytoprotective Effect of Trimetazidine on 75 min Warm Renal Ischemia-Reperfusion Injury in Rats

“…Our results indicate that the mechanism of protection is related to inhibition of lipid peroxidation. Also, Creagh et al [29] have reported that TMZ has a protective effect on ciclosporin-induced ischemic renal injury.…”

Trimetazidine: Experimental and Clinical Update Review

“…Boucher et al (17) and Opie and Boucher (59) have studied the effects of TMZ on ischemic contracture of isolated and perfused rat hearts induced by reduction of CF from 12 to 0.2 ml/min for 30 min, followed by 20-min reperfusion. A group of rats received TMZ 3 mgkg p.0.…”

“…Electrophysiological recordings of CAP were carried out in an anechoic chamber using a compact Mistral unit (Medelec International). The sound stimuli used were 10 ms filtered clicks at 16,12,8, and 4 kHz; the repetition rate was lO/s; the average was obtained from 64 samples and the analysis window was set at 20 ms. After physiological recordings, animals were deeply anesthetized and their cochleas quickly removed for morphological study. Study of the auditory threshold showed that the mean threshold value of the TMZ kainate group was significantly lower as compared to kainate-treated animals for all frequencies (p < 0.01 and p < 0.001 depending on the kHz values), whereas it was similar to that in the control group for 16 and 12 kHz, but higher for 8 and 4 kHz (p < 0.05).…”

“…In addition to ischemic injury caused to the graft by storage and reperfusion, organ toxicity due to immunosuppressive drugs may represent a significant concern, as is the case for cyclosporin A (CsA) nephrotoxicity. Creagh et al (16,17) have tested whether TMZ might prevent CsA nephrotoxicity in adult Greyhound dogs. The animals were subjected to four different treatments: unilateral nephrectomy (right kidney, group 1); removal of the right kidney plus occlusion of the left artery for 60 min (group 2); or the same protocol as for group 2 plus CsA 10 mg/kg/d i.v.…”

Prevention of gentamicin induced ototoxicity by trimetazidine in animal model

“…It was also reported that trimetazidine is affective in hepatic ischemia and neurotoxicity caused by cyclosprorine [10]. In general,…”