Protective Effects Of Trimetazidine Research Articles

Possible Protective Effect of Trimetazidine Alone and in Combination with Methotrexate in Attenuating Joint Inflammation in Freund’s Adjuvants Induced Rheumatoid Arthritis in Rats

Abstract Rheumatoid Arthritis is a complex chronic auto-immune systemic illness. It is primarily characterized by synovial hyperplasia and localized pro-inflammatory cytokine production that causes chronic synovitis and a long-lasting inflammation of the joints and bones. The study's goal was to look into the potential anti-arthritic effects of trimetazidine in a rat model of Freund’s complete adjuvant (FCA)-induced arthritis, which has many clinical and biochemical similarities to rheumatoid arthritis (RA). The underlying antirheumatoid arthritis mechanism, as well as its impact on TLR4/NFKB pathway were investigated to understand and confirm its potential efficacy in RA treatment. Our study was based on 4 groups, control group received saline injections, trimetazidine (7.2 mg/kg/day) treated group, methotrexate (0.75 mg/kg/week) treated group and combination group that received both medications in the same doses for 21 days. The degree of ipsilateral paw swelling, ankle diameter, body weight, tissue expression levels of TLR4(toll like receptor) and NFKB (nuclear factor kappa b) in paw, and serum ACPA (anticitrullinated protein antibodies) were all measured. With a slight but not statistically significant impact on ankle diameter, trimetazidine and methotrexate considerably reduced the arthritic symptoms as indicated by ipsilateral paw volume. It had no discernible impact on body weight. Together with the overall improved synovial hyperplasia and cartilage disarrangements, TLR4 and NFKB expression in synovial tissue were reduced. In a rat model of CFA-induced arthritis, trimetazidine displays a considerable anti- inflammatory impact that is even better than methotrexate and has the potential to be anti-arthritic. Additionally, there is a large additive effect between the two medications.

The protective effects of trimetazidine against ovary ischemia-reperfusion injury via the TLR4/Nf-kB signal pathway.

Late diagnosis and treatment of ovarian ischemia can lead to worsening of ischemia, irreversible damage to ovarian functions and infertility. In this process, there is no approved medical treatment that can reduce the negative effects of ischemia and contribute positively to ovarian functions during reperfusion after detorsion. Rats were randomly assigned into one of six groups of eight animals each. The groups were designed as follows: The control group, The ischemia(I) group, The Ischemia + Trimetazidine (I + TMZ) (20 mg/kg) group, and The ischemia-reperfusion group (I/R). The Ischemia-Reperfusion + Trimetazidine (I/R + TMZ) (20 mg/kg) group, and The Sham + Trimetazidine (Sham + TMZ) (20 mg/kg) group. In this study performed thiobarbituric acid reactive substances (TBARS), total thiol (-SH), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), toll-like receptor 4 (TLR4), and nuclear factor-kappa B(NF-κβ). Increased oxidative stress and inflammation were as a result of ovarian I and I/R application. Trimetazidine (TMZ), was sufficient to reduce the oxidative stress and inflammation. TLR4 and NF-κβ, which were upregulated by oxidative stress and inflammation, were regressed by TMZ. TMZ should be considered as a potential therapeutic agent in addition to surgery in the clinical treatment of ovarian torsion.

Protective Effect of Trimetazidine on Potassium Ion Homeostasis in Myocardial Tissue in Mice with Heart Failure.

The occurrence of heart failure (HF) is closely correlated with the disturbance of mitochondrial energy metabolism, and trimetazidine (TMZ) has been regarded as an effective agent in treating HF. Intracellular potassium ion (K+) homeostasis, which is modulated by K+ channels and transporters, is crucial for maintaining normal myocardial function and can be disrupted by HF. This study is aimed at exploring the protective effect of TMZ on K+ homeostasis within myocardial tissue in mice with HF. We observed the pathological changes of myocardial tissue under microscopes and further measured the content of adenosine triphosphate (ATP), the activity of Na+-K+ ATPase, and the expression of ATP1α1 at the mRNA and protein levels. Moreover, we also analyzed the changes in K+ flux across the myocardial tissue in mice. As a result, we found that there was a large amount of myocardial fiber lysis and fracture in HF myocardial tissue. Meanwhile, the potassium flux of mice with HF was reduced, and the expression of ATP1α1, the activity of Na+-K+ ATPase, and the supply and delivery of ATP were also decreased. In contrast, TMZ can effectively treat HF by restoring K+ homeostasis in the local microenvironment of myocardial tissues.

Protective Effect of Trimetazidine on Kidney Dysfunction: A Review of Experimental Evidence

Background and Objectives Acute kidney injury is the main cause of morbidity and mortality in the worldwide that is accompanied by short-term and long-term complications, including chronic kidney disease, end-stage renal disease, and ultimately death. Various mechanisms are involved in renal dysfunction, including oxidative stress, inflammatory responses, apoptosis, fibrosis, and mitochondrial dysfunction. Trimetazidine as a drug with free radical oxygen scavenging property represents to be more invaluable against acute kidney injury. Trimetazidine is considered as an anti-ischemic drug in the treatment of cardiac diseases which has been documented pharmacologic effects such as antioxidant, anti-apoptotic, and anti-inflammatory properties in renal ischemia-reperfusion injury, diabetic nephropathy, and nephrotoxicity models. Subjects and Methods This review underlines the nephroprotective effect of trimetazidine on kidney injury models. For this review, the articles have been searched in the databases, including PubMed, Scopus, Web of science, and Google Scholar. The search process was provided using these keywords: “Trimetazidine”, “kidney”, “nephrotoxicity”, “renal ischemia – reperfusion injury”, and “Protective.” Results Present study validates which trimetazidine as a potential agent alleviates kidney dysfunction in experimental models through several mechanisms. Conclusion Trimetazidine could be considered as promising candidate to treat a variety of kidney diseases in the future.

Protective effect of trimetazidine in radiation-induced cardiac fibrosis in mice.

Radiation-induced heart damage is a serious side effect caused by radiotherapy, especially during the treatment of cancer near the chest. Trimetazidine is effective at reducing inflammation in the heart, but how it affects radiation-induced cardiac fibrosis (RICF) is unknown. To investigate the potential effect and molecular mechanism, we designed this project with a C57BL6 male mouse model supposing trimetazidine could inhibit RICF in mice. During the experiment, mice were randomly divided into six groups including a control group (Con), radiation-damaged model group (Mod) and four experimental groups receiving low-dose (10 mg/kg/day) or high-dose (20 mg/kg/day) trimetazidine before or after radiation treatment. Apart from the control group, all mice chests were exposed to 6 MV X-rays at a single dose of 20 Gy to induce RICF, and tissue analysis was done at 8 weeks after irradiation. Fibroblast or interstitial tissues and cardiac fibrosis-like characteristics were determined using haematoxylin and eosin and Masson staining, which can be used to assess myocardial fibrosis. Immunohistochemical analysis and RT-PCR were used to determine gene expression and study the molecular mechanism. As a result, this study suggests that trimetazidine inhibits RICF by reducing gene expression related to myocyte apoptosis and fibrosis formation, i.e. connective tissue growth factor (CTGF), transforming growth factor (TGF)-β1, smad2 and smad3. In conclusion, by regulating the CTGF/TGF-β1/Smad pathway, trimetazidine could be a prospective drug for clinical treatment of RICF.

P6532Trimetazidine and nicorandil decrease the increment of serum creatinine in patients with normal or slightly decreased renal function after undergoing elective percutaneous coronary intervention

Abstract Background Contrast-induced nephropathy (CIN) is a serious complication of percutaneous coronary intervention which can cause serious adverse outcomes. There is still no effective treatment for it. Aims To evaluate and compare the protective effect of trimetazidine and nicorandil on renal function in patients undergoing percutaneous coronary intervention.with estimated glomerular filtration (eGFR) >60 ml/min/1.7 m2. Method 161 patients who met the inclusion criteria were recruited and divided into control group (n=41), trimetazidine group (n=40), nicorandil group (n=40) and trimetazidine combined with nicorandil group (n=40). Both TMZ and nicorandil were administered orally 72 hours before and 48 hours after the procedure. All patients in the four groups were given intravenous saline (0.9%) at a rate of 1 ml/kg/h 6 hours before and 12 hours after the procedure. Serum creatinine (SCr), GFR were measured before and 48 hours after the procedure. An increase of 44mmol/L (0.5mg/dL) in SCr or 25% higher than basal levels at 48 hours after administered iodinated CM was diagnosed as CIN. Results (1) The baseline characteristics of the four groups were similar. (2) The SCr levels increased in control group (baseline 73.07±15.69 VS. after PCI 91.71±23.10 mmol/L), TMZ group (baseline 71.90±17.30 VS. after PCI 82.00±17.19 mmol/L), nicorandil group (baseline 72.23±15.95 VS. after PCI 81.45±18.30 mmol/L)and TMZ plus nicorandil group (baseline 71.13±13.50 VS. after PCI 73.35±12.64 mmol/L) at 48 hours after the procedure, all p values <0.05. (3) The increment of SCr after PCI in control group (ΔScr=18.63±9.21 mmol/L) is higher than TMZ group (ΔScr=10.10±5.62 mmol/L) and nicorandil group (ΔScr=9.23±5.60mmol/L), and is higher than TMZ plus nicorandil group (ΔScr=2.23±1.42 mmol/L), all p values <0.001. There was no statistical difference of increment of SCr between TMZ group and nicorandil group. (4) Contrast-induced nephropathy developed in 14.6% (6/41) in control group, 2.5% (1/40) in TMZ group and 2.5% (1/40) in nicorandil group (p<0.05), none in TMZ plus nicorandil group. Conclusions TMZ and nicorandil exerted similar protective effect on renal function by decreasing SCr level and CIN incidence after PCI. The efficacy of TMZ combined with nicorandil on renal protection was greater than TMZ or nicorandil alone.

Protective Effects of Trimetazidine in Retarding Selenite-Induced Lens Opacification

ABSTRACTPurpose: Cataracts are the leading cause of vision loss worldwide, and the over-production of reactive oxygen species (ROS) is the foremost underlying cause of cataracts. Reducing ROS levels can efficiently prevent lens opacification, as evidenced by many studies. Here, we inhibited ROS overproduction with trimetazidine (TMZ), which is an antioxidant, to explore the therapeutic effects of TMZ and the mechanism of lens opacification.Materials and methods: Sodium selenite-induced cataract formation resulted in a significant loss of lens transparency. This effect could be efficiently rescued by TMZ, which was further found to be an inhibitor of ROS production, as determined by assaying oxidative stress-related parameters (SOD activity, MDA, ·OH and H2O2 levels) during cataract formation. The experimental protocols involving animal research were approved by the Animal Care and Ethics Committee of Wenzhou Medical University and conducted according to the Association for Research in Vision and Ophthalmology under the guidelines of the Animal Welfare Act (SYXK 2015–0009).Results: Our study found that TMZ can retard the onset and progression of lens opacification in vivo in experiments using Sprague-Dawley (SD) suckling rats and can rescue the morphology of HLEB3 cells in vitro. The flow cytometry and DNA fragmentation assays showed that TMZ could prevent sodium selenite-induced apoptosis. The western blot analysing showed that the levels of apoptosis-associated Bcl-2 and Nrf2 were dramatically decreased following the sodium selenite treatment. In addition, the bisulfate DNA sequencing revealed that the demethylation of CpGs in the promoter region of Keap1 was stimulated, and that this demethylation could be inhibited by TMZ by rescuing the Nrf2 expression level.Conclusions: Our findings indicate that the antioxidant TMZ strongly reduces ROS production, which ultimately delays the progression of cataract formation, suggesting that treatment with TMZ represents a novel, promising antioxidant protection to retard cataract formation.

Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction.

Objective:The objective of this study was to investigate the effects of trimetazidine (TMZ) and coenzyme Q10 (CoQ10) on cisplatin-induced cardiotoxicity in rat cardiomyocytes.Methods:Rat cardiomyocytes were isolated and subjected to cisplatin (200 µM) treatment with and without TMZ (200 µM) and CoQ10 (200 mg/L) pretreatment. The cell viability, apoptosis, oxidant and antioxidant indicators, and mitochondrial dysfunction were examined.Results:TMZ or CoQ10 significantly attenuated cisplatin-induced cell viability inhibition (p<0.01) and apoptosis (p<0.001), and the combined use of TMZ and CoQ10 pretreatment exerted a pronounced effect compared to the effects of using each of these agents individually (p<0.05). TMZ or CoQ10 inhibited the levels of reactive oxidative species (ROS, p<0.01) and malondialdehyde (MDA, p<0.001 and p<0.01, respectively), elevated the activities of antioxidant enzymes superoxide dismutase (SOD, p<0.01) and catalase (CAT, p<0.01 and p<0.05, respectively), evidently enhanced nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2, p<0.05), alleviated mitochondrial membrane potential (ΔΨm) loss (p<0.05), and down-regulated the release of cytochrome c (cyto-c) into the cytosol (p<0.01) in cisplatin-treated cells. The combined use of TMZ and CoQ10 treatment was more effective than using either agent alone (p<0.01 for ROS, MDA, CAT, and cytosolic cyto-c; p<0.05 for SOD, nuclear Nrf2, and ΔΨm loss).Conclusion:TMZ and CoQ10 showed protective effects against cisplatin-induced cardiotoxicity via attenuating oxidative stress.

Protective Effects of Trimetazidine Against Acetaminophen-Induced Liver Injury in Mice

Protective Effects of Trimetazidine Against Acetaminophen-Induced Liver Injury in Mice

Trimetazidine in Practice: Review of the Clinical and Experimental Evidence.

All of the following traditional agents for the management of stable angina pectoris include the symptomatic treatment with heart rate–lowering agents such as β-blockers or non-dihydropyridine Ca-channel blockers, or ivabradine—the first selective sinus node If channel inhibitor—vasodilatators and preventive use of angiotensin-converting enzyme inhibitors affect the parameters of circulation directly. Trimetazidine exerts its anti-ischemic action by modulating cardiac metabolism without altering the hemodynamic functions, therefore represents an excellent complementary potential to the conventional angina treatment. It has a beneficial effect on the inflammatory profile and endothelial function and shows diverse benefits by reducing the number and the intensity of angina attacks and improving the clinical signs and symptoms of myocardial ischemia given as monotherapy as well as combined with other antianginal agents. Patients undergoing coronary revascularization procedures or with comorbid left ventricular dysfunction and diabetes mellitus also benefit from the protective effects of trimetazidine.

The protective effect of trimetazidine against cisplatin-induced nephrotoxicity in rats.

Nephrotoxicity is a dose-limiting side effect of cisplatin (CSP). The study investigated the possible protective role of trimetazidine (TMZ) against CSP-induced nephrotoxicity in rats. Rats were divided into four groups; control, TMZ, CSP, and CSP + TMZ. The CSP group showed significant deterioration in kidney function with structural changes in the form of interstitial hemorrhage, glomeruli shrinkage and peritublar capillary congestion, tubular cells vacuolation, pyknosis, shedding and necrosis, and inflammatory cell infiltrates, all indicating renal damage. CSP also caused a significant increase in the lipid peroxidation marker malondialdehyde (MDA) levels, renal nuclear factor kappa B (NF-κB) DNA-binding activity and protein expression, and tumor necrosis factor alpha (TNF-α) and IL-6 levels. Treatment with TMZ before and after CSP injection produced significant improvement of kidney function and histopathology. TMZ treatment also significantly attenuated CSP-induced oxidative stress and suppressed elevated levels of TNF-α and IL-6 and NF-κB expression and its DNA-binding activity caused by CSP administration. TMZ has a protective effect against CSP-induced nephrotoxicity mediated by reduction of oxidative stress and attenuation of CSP-induced inflammation.

The protective effect of trimetazidine on myocardial ischemia/reperfusion injury through activating AMPK and ERK signaling pathway

IntroductionTrimetazidine (TMZ) is an anti-anginal drug that has been widely used in Europe and Asia. The TMZ can optimize energy metabolism via inhibition of long-chain 3-ketoacyl CoA thiolase (3-KAT) in the heart, with subsequent decrease in fatty acid oxidation and stimulation of glucose oxidation. However, the mechanism by which TMZ aids in cardioprotection against ischemic injury has not been characterized. AMP-activated protein kinase (AMPK) is an energy sensor that controls ATP supply from substrate metabolism and protects heart from energy stress. TMZ changes the cardiac AMP/ATP ratio by modulating fatty acid oxidation, thereby triggering AMPK signaling cascade that contributes to the protection of the heart from ischemia/reperfusion (I/R) injury. MethodsThe mouse model of in vivo regional ischemia and reperfusion by the ligation of the left anterior descending coronary artery (LAD) was used for determination of myocardial infarction. The infarct size was compared between C57BL/6J WT mice and AMPK kinase dead (KD) transgenic mice with or without TMZ treatment. The ex vivo working heart perfusion system was used to monitor the effect of TMZ on glucose oxidation and fatty acid oxidation in the heart. ResultsTMZ treatment significantly stimulates cardiac AMPK and extracellular signal-regulated kinase (ERK) signaling pathways (p<0.05 vs. vehicle group). The administration of TMZ reduces myocardial infarction size in WT C57BL/6J hearts, the reduction of myocardial infarction size by TMZ in AMPK KD hearts was significantly impaired versus WT hearts (p<0.05). Intriguingly, the administration of ERK inhibitor, PD98059, to AMPK KD mice abolished the cardioprotection of TMZ against I/R injury. The ex vivo working heart perfusion data demonstrated that TMZ treatment significantly activates AMPK signaling and modulating the substrate metabolism by shifting fatty acid oxidation to glucose oxidation during reperfusion, leading to reduction of oxidative stress in the I/R hearts. Therefore, both AMPK and ERK signaling pathways mediate the cardioprotection of TMZ against ischemic injury. The metabolic benefits of TMZ for angina patients could be due to the activation of energy sensor AMPK in the heart by TMZ administration.

Protective effects of trimetazidine on thioacetamide-induced hepatic encephalopathy in rats

Protective effects of trimetazidine on thioacetamide-induced hepatic encephalopathy in rats

Different Protective Effects of Trimetazidine against Renal Ischemia/Reperfusion Injury in Rats

Ischemia/Reperfusion (I/R) injury during kidney transplantation is a major clinical problem which leads to delayed graft function or even graft rejection. Therefore, the aim of the present study was to explore the possible protective effects of trimetazidine, an anti-ischemic agent, against experimentally-induced renal I/R injury in rats. Ischemia was induced by bilateral clamping of renal pedicles for 45 min followed by 24 h of reperfusion. Trimetazidine (10 mg/kg) was orally administered twice daily for 14successive days before induction of ischemia. At the end of the reperfusion period (24 h), blood and renal tissue samples were collected for biochemical and histopathological examination. Trimetazidine showed nephroprotective effects as evidenced by significant decrease in blood urea nitrogen and serum creatinine levels as well as renal content of tumor necrosis factor-α, malondialdehyde and myeloperoxidase. In addition, trimetazidine replenished renal content of adenosine triphosphate and glutathione that was confirmed by the improvement in histopathological features. The current study demonstrated the nephroprotective effects of trimetazidine against renal I/R injury, which might be mediated through its anti-ischemic, anti-inflammatory or antioxidant activities.

Protective effects of trimetazidine on bone marrow mesenchymal stem cells viability in an ex vivo model of hypoxia and in vivo model of locally myocardial ischemia

Bone marrow mesenchymal stem cells (MSCs) have shown potential for cardiac repair following myocardial injury, but this approach is limited by their poor viability after transplantation. The present study was to investigate whether trimetazidine (TMZ) could improve survival of MSCs in an ex vitro model of hypoxia, as well as survival, differentiation, and subsequent activities of transplanted MSCs in rat hearts with acute myocardial infarction (AMI). MSCs at passage 3 were examined for their viability and apoptosis under a transmission electron microscope, and by using flow cytometry following culture in serum-free medium and exposure to hypoxia (5% CO(2), 95% N(2)) for 12 h with or without TMZ. Thirty Wistar rats were divided into 3 groups (n=10 each group), including group I (AMI control), group II (MSCs transplantation alone), and group III (TMZ+MSCs). Rat MSCs (4×10(7)) were injected into peri-infarct myocardium (MSCs group and TMZ+MSCs group) 30 min after coronary artery ligation. The rats in TMZ+MSCs group were additionally fed on TMZ (2.08 mg·kg(-1)·day(-1)) from day 3 before AMI to day 28 after AMI. Cardiac structure and function were assessed by echocardiography at 28th day after transplantation. Blood samples were collected before the start of TMZ therapy (baseline), and 24 and 48 h after AMI, and inflammatory cytokines (CRP, TNF-α) were measured. Then the survival and differentiation of transplanted cells in vivo were detected by immunofluorescent staining. The cellular apoptosis in the peri-infarct region was detected by using TUNEL assay. Furthermore, apoptosis-related proteins (Bcl-2, Bax) within the post-infarcted myocardium were detected by using Western blotting. In hypoxic culture, the TMZ-treated MSCs displayed a two-fold decrease in apoptosis under serum-free medium and hypoxia environment. In vivo, cardiac infarct size was significantly reduced, and cardiac function significantly improved in MSCs and TMZ+MSCs groups as compared with those in the AMI control group. Combined treatment of TMZ with MSCs implantation demonstrated further decreased MSCs apoptosis, further increased MSCs viability, further decreased infarct size, and further improved cardiac function as compared with MSCs alone. The baseline levels of inflammatory cytokines (CRP, TNF-α) had no significant difference among the groups. In contrast, all parameters at 24 h were lower in TMZ+MSCs group than those in MSCs group. Furthermore, Western blotting indicated that the expression of anti-apoptotic protein Bcl-2 was up-regulated, while the pro-apoptotic protein Bax was down-regulated in the TMZ+MSCs group, compared with that in the MSCs group. It is suggested that implantation of MSCs combined with TMZ treatment is superior to MSCs monotherapy for MSCs viability and cardiac function recovery.

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

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.

RETRACTED: Effect of trimetazidine on renal ischemia/reperfusion injury in rats

There is increasing evidence to suggest that toxic oxygen radicals play a role in the pathogenesis of ischemia/reperfusion (I/R) injury in the kidney. This study was designed to investigate the effects of trimetazidine, in I/R induced renal failure in rats. The protective effect of trimetazidine (Tmz) against the damage inflicted by reactive oxygen species (ROS) during renal I/R was investigated in Sprague-Dawley rats using histopathological and biochemical parameters. In one set of experiments animals were unilaterally nephrectomized, and subjected to 45 min of left renal pedicle occlusion and in another set both the renal pedicles were occluded for 45 min followed by 24 h of reperfusion. Trimetazidine (3 mg kg(-1), i.p.) was administered 30 min prior to ischemia and repeated 12 h after the first dose. At the end of the reperfusion period, rats were sacrificed. Thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) levels, glutathione reductase (GR) catalase (CAT), and superoxide dismutase (SOD) activities were determined in renal tissue. Serum creatinine and blood urea nitrogen (BUN) concentrations were measured for the evaluation of renal function. Ischemic control animals demonstrated severe deterioration of renal function, renal morphology and a significant renal oxidative stress. Pretreatment of animals with trimetazidine markedly attenuated renal dysfunction, morphological alterations, reduced elevated TBARS levels and restored the depleted renal antioxidant enzymes. The findings imply that ROS play a causal role in I/R induced renal injury and trimetazidine exert renoprotective effects probably by the radical scavenging and antioxidant activities.

SOMATOSENSORY EVOKED POTENTIAL AND HISTOPATHOLOGICAL INVESTIGATIONS IN ISCHAEMIA-INDUCED BRAIN DAMAGE: EFFECTS OF TRIMETAZIDINE IN RATS

We studied the protective effects of trimetazidine (TMZ) on brain damage by means of somatosensory evoked potentials (SEP) in rats. The TMZ group did not show any statistically significant difference from the control group with respect to SEPs. However, the percentage of cells with ischaemic cell damage in hippocampal regions was significantly smaller in the TMZ group than the control group. Trimetazidine reduced the number of damaged cells in the cerebral tissue during the ischaemia-reperfusion damage. It was suggested that higher doses of trimetazidine may further reduce the number of cells with ischaemic damage.

Protective Effect of Trimetazidine in a Model of Ischemia-Reperfusion in the Rat Retina

Trimetazidine is an anti-ischemic agent which is frequently prescribed as a prophylactic treatment of episodes of angina pectoris and as a symptomatic treatment of vertigo and tinnitus. It has also shown beneficial effects in models of visual dysfunction, but the mechanism(s) by which this occurs is as yet undefined. The present study was intended to evaluate the influence of trimetazidine on retinal damage induced by ischemia-reperfusion in a rat model. Retinal ischemia was induced by increasing intraocular pressure to 160 mm Hg for 60 min. Trimetazidine or buffer controls were administered 3 days before the ischemia or in the postischemic period. The degree of retinal damage was assessed after 15 and 30 days of reperfusion after the ischemic insult by histopathologic study according to Hughes’ quantification of ischemic damage. Retinal ischemia led to significant reductions in thickness and cell number, mainly in the inner retinal layers. The results from the study demonstrate that treatment with intraperitoneally injected trimetazidine conferred significant protection against retinal ischemic damage. Better results were obtained in the pretreatment group after 15 days of reperfusion. Trimetazidine protects the rat retina from pressure-induced ischemic injury and might be considered a potential therapeutic modality for combating retinal ischemia.

Protective effects of trimetazidine in acute hypoxia

Trimetazidine improves resistance to acute hypobaric hypoxia. Intraperitoneal injection of this preparation in an optimal protective dose (25 mg/kg) to rats prevents serious disturbances of energy metabolism and activation of lipid peroxidation in the brain, heart, and liver.