Combined ß-sitosterol and trimetazidine mitigate potassium dichromate-induced cardiotoxicity in rats through the interplay between NF-κB/AMPK/mTOR/TLR4 and HO-1/NADPH signaling pathways.

Hexavalent chromium salt, like potassium dichromate (PD), is chromium's most precarious valence state in industrial wastes. Recently, there has been increasing interest in ß-sitosterol (BSS), a bioactive phytosterol, as a dietary supplement. BSS is recommended in treating cardiovascular disorders due to its antioxidant effect. Trimetazidine (TMZ) was used traditionally for cardioprotection. Through the administration of BSS and TMZ, the cardiotoxic effects of PD were to be countered in this study, in addition to examining the precise mechanism of PD-induced cardiotoxicity. Thirty male albino rats were divided into five groups; the control group: administered normal saline daily (3 mL/kg); the PD group: administered normal saline daily (3 mL/kg); BSS group: administered BSS daily (20 mg/kg); TMZ group: administered TMZ daily (15 mg/kg); and the BSS + TMZ group: administered both BSS (20 mg/kg) and TMZ (15 mg/kg) daily. All experimental groups, except the control, received on the 19th day a single dose of PD (30 mg/kg/day, S.C.). Normal saline, BSS, and TMZ were received daily for 21 consecutive days p.o. The exposure to PD promoted different oxidative stresses, pro-inflammatory, and cardiotoxicity biomarkers. BSS or TMZ succeeded solely in reducing these deleterious effects; however, their combination notably returned measured biomarkers close to normal values. The histopathological investigations have supported the biochemical findings. The combination of BSS and TMZ protects against PD cardiotoxicity in rats by reducing oxidative stress and apoptotic and inflammatory biomarkers. It may be promising for alleviating and protecting against PD-induced cardiotoxicity in people at an early stage; however, these findings need further clinical studies to be confirmed. HIGHLIGHTS: • Potassium dichromate induces cardiotoxicity in rats through the upregulation of oxidative stress, proinflammatory, and apoptotic pathways biomarkers. • ß-Sitosterol possesses a possible cardioprotective effect by modulating several signaling pathways. • Trimetazidine, the antianginal agent, has a potential cardioprotective impact on PD-intoxicated rat model. • The combination of ß-Sitosterol and trimetazidine was the best in modulating different pathways involved in PD cardiotoxicity in rats via the interplay between NF-κB/AMPK/mTOR/TLR4 and HO-1/NADPH signaling pathways.

Metabolic study of trimetazidine using ultra-high performance liquid chromatography-tandem mass spectrometry

Abstract In the present study, the application of ultra-high performance liquid chromatography-tandem mass spectrometry allowed us to study of known-as well as hitherto unknown-trimetazidine (TMZ) metabolites in human urine and to propose their renal excretion profiles. Urine samples from a healthy volunteer were analyzed at baseline and at 0-4 h, 4-8 h, 8-12 h, and 12-24 h after a single dose of TMZ. A dilute-and-shoot procedure was used as sample treatment before separation. Full-scan spectra of possible metabolites were acquired. Additionally, product ion scan spectra of precursor ions of interest were also acquired at two collision energies. Intact TMZ was a major excretion product, with a maximum concentration at 4-8 h after administration. Moreover, five minor metabolites were observed, namely trimetazidine-N-oxide (M1), N-formyl trimetazidine (M2), desmethyl-trimetazidine O-sulfate (M3), desmethyl-trimetazidine O-glucuronide (M4), and desmethyl-trimetazidine-N-oxide-O-glucuronide (M5). Metabolite M5 has not previously been reported. Excretion curves were constructed based on the chromatographic peak areas of specific mass transitions (precursor ion > product ion) related to each of the detected metabolites

Observation of Curative Effect of Trimetazidine Combined with Metoprolol in Elderly Patients with Coronary Heart Disease Complicated with Heart Failure and the Effect of Myocardial Remodeling by Integrated Traditional Chinese and Western Medicine.

Diabetic retinopathy (DR) is the most common complication of diabetes and is often characterized by damage to retinal vascular microcirculation, resulting in retinal exudation, hemorrhage, fibrosis, and neovascularization. With the aging of my country's population, the incidence of DR is increasing year by year, and it has become one of the main blinding eye diseases in ophthalmic diseases also tends to be younger. So far, although the pathogenesis of DR is not completely clear, scholars generally believe that DR is based on the disorder of glucose metabolism, causing changes in the microcirculation of ocular tissues, nerves, and blood vessels, resulting in chronic damage to the nutrition and visual function of the eye disease. In order to explore the demand for cardiovascular disease treatment, make up for the lack of chronic diseases affecting people's physical harm, and improve the success rate of cardiovascular disease treatment, a method to observe the efficacy and myocardial remodeling of trimetazidine combined with metoprolol in elderly patients with coronary heart disease and heart failure based on integrated traditional Chinese and Western medicine was proposed. 54 elderly people over 60 years old are afraid of cardiovascular disease and take active protection. A method based on observation of integrated traditional Chinese and Western medicine was proposed, and at the same time, an intelligent medical monitoring system was constructed to better study, observe, and improve the efficacy of trimetazidine combined with metoprolol in elderly patients with coronary heart disease, heart failure, and myocardial impact of refactoring. The results of the study show that trimetazidine has a good clinical effect on ischemic cardiomyopathy heart failure based on the observation of integrated traditional Chinese and Western medicine.

Beneficial effect of trimetazidine on folic acid-induced acute kidney injury in mice: Role of HIF-1α/HO-1.

Acute kidney injury (AKI) is a complex syndrome associated with a decrease in renal function and a significant impact on patient outcomes. Injection of folic acid (FA) in mice is used for studying the pathogenesis of AKI. This study investigated the impact of trimetazidine (a metabolic modulator-antianginal drug; TMZ), against FA-induced AKI. AKI was induced by FA (250 mg/kg, ip) in mice. Two doses of TMZ were administered orally for 10 days. Administration of TMZ at a high dose (20 mg/kg) exhibited significant decreases in the renal somatic index (RSI), serum levels of lactate dehydrogenase (LDH), creatinine (Cr), blood urea nitrogen (1), and proteins level in urine. Moreover, TMZ significantly increased creatinine clearance (CCr), serum albumin, urine creatinine, and urine urea levels. This improvement in markers of kidney damage was associated with marked renal antioxidant effects (↓NO and ↓lipid peroxidation, normalized reduced glutathione (GSH) level and superoxide dismutase (SOD) activity, and increased HIF-1α/HO-1 level). Furthermore, TMZ significantly decreased FA-induced expression of MPO and inflammatory cytokine IL-18, TNF-α, and NF-κB p65 subunit. Renal apoptosis, along with apoptotic markers, were enhanced by FA injection and suppressed by TMZ administration (↓Caspase-3, ↓Bax, and ↑Bcl2 expression). Finally, TMZ amended FA-induced histopathological changes in kidneys. By mitigating functional alteration, oxidative stress, and preventing the development of inflammatory and apoptosis signals, TMZ provides dose-dependent defense against FA-induced AKI mainly via stimulation of hypoxia-inducible factor-1 alpha (HIF-1α)/heme oxygenase-1 (HO-1) pathway.

The inhibitory effect of trimetazidine on detrusor contractility - a potential repositioning of trimetazidine for the treatment of overactive bladder.

OBJECTIVES: This study aimed to identify the effect of trimetazidine (TMZ), an antianginal drug, on detrusor smooth muscle (DSM) contractility and its possible mechanisms of action. METHODS: We performed in-vitro contractility studies on isolated mouse DSM strips and investigated the effect of TMZ on Ca2+ levels in fura-2-loaded A7r5 cells. KEY FINDINGS: TMZ (300 or 1000 µM) inhibited carbachol (CCh)- and KCl-induced contractions and produced a concentration-dependent (10-1000 µM) relaxation in KCl-precontracted DSM strips. TMZ-induced relaxation was markedly decreased by BaCl2, an inward-rectifying K+ channel blocker, but was not altered by preincubation with tetraethylammonium, glibenclamide, 4-aminopyridine, propranolol, L-NAME or methylene blue. TMZ (300 or 1000 µM) reduced both the CaCl2-induced contraction of depolarized DSM strips under Ca2+-free conditions and the CCh-induced contraction of DSM strips preincubated with nifedipine in Ca2+-containing Krebs solution. Furthermore, TMZ (1000 µM) significantly decreased the Ca2+ levels in fura-2-loaded A7r5 cells. CONCLUSIONS: TMZ decreased DSM contractility and caused a concentration-dependent relaxation of the tissue possibly through its actions on Ca2+ transients and K+ channels. Our results provide preclinical evidence that TMZ would be a potential candidate to treat disorders related to the overactivity of the bladder.

Trimetazidine an emerging paradigm in renal therapeutics: Preclinical and clinical insights.

Trimetazidine (TMZ) is a well-known anti-ischemic agent used for the treatment of angina pectoris. In the past decades, the efficacy of this drug has been tested in a wide range of kidney injuries, including drug-induced nephrotoxicity (DIN), radio-contrast agent-induced nephropathy, and surgically induced renal ischemic injury. TMZhas renoprotective effects by attenuating oxidative stress, inflammatory cytokine release, maintaining oxygen and energy balance. Moreover, TMZ administration prevented kidney graft rejection in the porcine model by suppressing the infiltration of mononuclear cells, preserving mitochondrial functions, and maintaining Ca+ homeostasis. In DIN and diabetic kidney diseases,TMZ treatment prevents renal injury by inactivating immune cells, attenuating renal fibrosis, inflammation, apoptosis, and histological abnormalities. Interestingly, the clinical therapeutic efficacy of TMZ has also been documented in pre-existing kidney disease patients undergoing contrast exposure for diagnostic intervention. However, the mechanistic insights into the TMZ mediated renoprotective effects in other forms of renal injuries, including type-2 diabetes, drug-induced nephrotoxicity, and hypertension-induced chronic kidney diseases, remain uninvestigated and incomplete. Moreover, the clinical utility of TMZ as a renoprotective agent in radio-contrast-induced nephrotoxicity needs to be tested in a large patient population. Nevertheless, the available pieces of evidence suggest that TMZ is a promising and emerging renal therapy for the treatment and management of kidney diseases of variable etiologies. This review discusses the various pre-clinical and clinical findings and provides mechanistic insights into the TMZ mediated beneficial effects in various kidney diseases.

Compound danshen dripping pills combined with trimetazidine in treating unstable angina pectoris: Protocol for a systematic review of randomized controlled trials.

BACKGROUND: Compound danshen dripping pills (CDDP) and trimetazidine (TMZ) are commonly used in the treatment of unstable angina pectoris (UAP). Currently, the combination of CDDP and TMZ has been widely used for UAP. However, the clinical evidence CDDP combined with TMZ for treating UAP is not sufficient. METHODS: We searched for randomized controlled trials testing CDDP combined with TMZ for the treatment of UAP in Chinese National Knowledge Infrastructure database, VIP database, Chinese Biological and Medicine database, Wangfang database, MEDLINE, EMBASE, Cochrane Library, and Web of Science. Extracted data are analyzed using Review Manager 5.3 software. The quality evaluation, forest plots and funnel plots will be conducted by RevMan5.3 software. Moreover, subgroup analysis and sensitivity analysis will also be completed by RevMan5.3. RESULTS: This systematic review will provide powerful clinical evidence of combination CDDP and TMZ for treating UAP. CONCLUSIONS: This systematic review will be provided up-to-date clinical evidence to evaluate the effectiveness and safety of CDDP combined with TMZ for the treatment of parents with UAP.Registration Number: PROSPERO CRD42019143100.

Therapeutic efficacy and safety of Shexiang Baoxin Pill combined with trimetazidine in elderly patients with heart failure secondary to ischaemic cardiomyopathy: A systematic review and meta-analysis.

BACKGROUND: Shexiang Baoxin Pill (SBP) is one of the most commonly used traditional Chinese patent medicines for cardiovascular diseases. This systematic review was designed to provide rigorous therapeutic efficacy and safety evidence on the use of SBP combined with trimetazidine in elderly patients with heart failure (HF) secondary to ischaemic cardiomyopathy (ICM). METHODS: Relevant randomized controlled trials (RCTs) investigating the clinical efficacy of SBP combined with trimetazidine in treating ICM-associated HF were widely searched in electronic databases, including PubMed, Cochrane library, EMBASE, CBM, CNKI, VMIS, and Wanfang up to January 1, 2018. The methodological quality of each trial was assessed according to the Cochrane Reviewers' Handbook 5.0. Meta-analysis was performed by using Review Manager 5.3. RESULTS: Eighteen RCTs (N = 1532) that met the criteria were included in the review for the assessment of methodological quality. Meta-analysis showed that, when compared with conventional therapy, SBP combined with trimetazidine significantly improved the clinical efficacy and indices of cardiac function (including increasing left ventricular ejection fraction [LVEF] and 6-minute walk distance [6-MWD], decreasing left ventricular end-diastolic diameter [LVEDD] and left ventricular end-systolic diameter [LVESD]) without serious adverse reactions. CONCLUSION: This work provides evidence of the benefit of SBP combined with trimetazidine for the treatment of HF secondary to ICM. More high quality and well-designed RCTs are needed to confirm these findings.

Trimetazidine ameliorates myocardial ischemia-reperfusion injury.

Aim of this study was to investigate the effects of trimetazidine attenuating the myocardial ischemia-reperfusion injury to myocardium in rats and the underlying mechanisms. A model of myocardial ischemia reperfusion was established via ligating the left anterior descending coronary artery in 30 rats, and then they were randomly assigned to model group (n=10), low dose group (n=10) and high dose group (n=10). Moreover, additional 10 rats were collected and allocated to sham operation group, which was served as control group. Then, rats in the low dose group and high dose group were given trimetazidine with the dose of 10mg/kg and 30mg/kg respectively by intragastric administration, while rats in the control group and model group were given the equivalent volume saline. The dose was given once a day for consecutive 4 weeks in all rats. Echocardiography was applied to evaluate cardiac function, including left ventricular end-systolic dimension (LVESD), left ventricular end diastolic dimension (LVEDD) and left ventricular ejection fraction (LVEF). Next, myocardial tissue was collected, and Bax and Bcl-2 mRNA and the protein levels in the four groups were detected by RT-PCR and Western blot respectively. The level of malonaldehyde (MDA) and super oxide dismutase (SOD) activity in rat myocaridum in each group were detected by colorimetric methods, while the variables of apoptosis were measured by TUNEL methods. In comparison with the control group, LVEDD, LVEDS of rats increased significantly, LVEF decreased obviously, as well as Bax level, MDA level and the apoptotic variables in myocardial tissue increased (P<0.05), but Bcl-2 level and SOD activity decreased significantly in low dose, high dose and model group (P<0.05). Compared with model group, LVEDD, LVEDS of rats decreased obviously, LVEF increased significantly, as well as Bax level, MDA level and the apoptotic variables in myocardial tissue decreased (P<0.05), but Bcl-2 level and SOD activity increased significantly in low dose group, high dose group (P<0.05). The regulatory role of trimetazidine on above indicators of rats was in a dose-dependent manner. Trimetazidine can ameliorate rat myocardium following ischemia-reperfusion injury by effectively attenuating the injury from myocardial cell apoptosis; meanwhile, it can resist cell apoptosis through regulating Bax and bcl-2 expression, which exhibits guiding significance for the treatment of myocardial ischemia and reperfusion.

Anxiolytic Properties of Trimetazidine in Experimental Models of Increased Anxiety.

Effect of trimetazidine (20 and 30 mg/kg) on elevated plus maze behavior of rodents was assessed in the genetic and pharmacological anxiety models. Single intraperitoneal injection of trimetazidine in a dose of 20 mg/kg prevented anxiety development in highly emotional male BALB/c mice and increased the time spent in open arms of the maze. In outbred male rats receiving 10% ethanol solution for 20 weeks, trimetazidine administered intraperitoneally in a dose of 20 mg/kg for 28 days abolished ethanol withdrawal-induced anxiogenesis developed against the background of 4-week alcohol deprivation: it increased the time spent in open arms, the number of entries into open arms, and total locomotor activity in the maze. Anxiolytic properties of trimetazidine were not inferior to those of the non-benzodiazepine anxiolytic Afobazole (fabomotizole) in acute and chronic administration.

Real-world Evidence for the Antianginal Efficacy of Trimetazidine from the Russian Observational CHOICE-2 Study.

INTRODUCTION: The guidelines recommend a beta-blocker or calcium channel blocker as the first-line medication for angina, supplemented by other agents for additional symptoms. One such agent is trimetazidine (TMZ), which has been shown to reduce the frequency of anginal episodes and improve exercise performance without affecting haemodynamic parameters. However, extensive real-world evidence for its efficacy in combination with first-line therapies has been lacking. METHODS: The aim of this large-scale, Russian, multicentre, 6-month, open-label, prospective observational study was to assess the effect of adding TMZ modified release 35 mg bid to background antianginal therapy in the real-world clinical setting. RESULTS: The study included 896 patients: 54% women, aged 29-90 years (42.6% >65 years), 63% with class II angina, and receiving beta-blockers alone or in combination (93%). Add-on TMZ reduced angina frequency and short-acting nitrate use within 2 weeks (both p < 0.0001) regardless of background therapy and maintained this effect over 6 months. It increased the proportion of patients with class I angina sixfold while decreasing that of class 3 angina almost fourfold. It also improved walking distance and well-being at 6 months (both p < 0.0001). Treatment was well tolerated. CONCLUSION: Add-on TMZ is a safe and rapidly effective treatment for reducing angina attacks and nitrate use in the real-world clinical setting. It also increases exercise capacity and well-being. These effects are observed within 2 weeks and persist for at least 6 months.

Metabolic support for the heart: complementary therapy for heart failure?

The failing heart has an increased metabolic demand and at the same time suffers from impaired energy efficiency, which is a detrimental combination. Therefore, therapies targeting the energy-deprived failing heart and rewiring cardiac metabolism are of great potential, but are lacking in daily clinical practice. Metabolic impairment in heart failure patients has been well characterized for patients with reduced ejection fraction, and is coming of age in patients with 'preserved' ejection fraction. Targeting cardiomyocyte metabolism in heart failure could complement current heart failure treatments that do improve cardiovascular haemodynamics, but not the energetic status of the heart. In this review, we discuss the hallmarks of normal cardiac metabolism, typical metabolic disturbances in heart failure, and past and present therapeutic targets that impact on cardiac metabolism.

Effects of atorvastatin combined with trimetazidine on myocardial injury and inflammatory mediator in unstable angina patients during perioperative of percutaneous coronary intervention.

OBJECTIVE: To investigate the effects of atorvastatin combined with trimetazidine on periprocedural myocardial injury and serum inflammatory mediators in unstable angina pectoris (UAP) patients following percutaneous coronary intervention (PCI) treatment. PATIENTS AND METHODS: 90 patients with UAP treated with conventional medications and PCI were recruited and were randomly divided into the control group and the experimental group. The control group had 42 patients were treated with atorvastatin alone, while the experimental group had 48 cases treated with atorvastatin combined with trimetazidine. All the patients were checked the preoperative 24h and postoperative 24h PCI concentrations of cardiac troponin I (cTnI), hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), serum interferon-γ (IFN-γ) and interlukin-10 (IL-10). RESULTS: At the pre-PCI stage, every serum factors was no significant difference. 24 hours after the PCI intervention, the occurence of abnormal cTnI level in the experimental group was remarkable reduced than the control group. In the experimental group, the serum levels of TNF-α and IFN-γ significantly decreased (p < 0.05); while IL-10 was increased. In the control group, all the mediators were increased significantly except the hs-CRP (p < 0.05). CONCLUSIONS: No unexpected symptom was found in patients with large dose atorvastatin combined with large dose trimetazidine. The administration of conventional medications together with the atorvastatin plus trimetazidine were able to reduce the prevalence of postoperative myocardial injury.

Efficacy of medical therapy in the prevention of residual dizziness after successful repositioning maneuvers for Benign Paroxysmal Positional Vertigo (BPPV).

OBJECTIVES: The aim of this study was to investigate the efficacy of trimetazidine, betahistine, and ginkgo biloba extract in the treatment of residual dizziness after successful repositioning maneuvers for benign paroxysmal positional vertigo. METHODOLOGY: This was a randomized controlled clinical trial. Complete clinical data were analyzed from 100 patients (27 men and 73 women; mean age 52.16 ± 13.2 years, range 11-80 years) with BPPV who underwent succcessful repositioning maneuvers and then received betahistine, trimetazidine, gingko biloba extract, or no medication (n = 25 for each group) for 1 week. On days 1, 3, and 5 after the repositioning maneuver, scores obtained from the Dizziness Handicap Inventory (DHI) questionnaire were compared. RESULTS: There were no statistically significant differences in the premedication DHI scores of patients with residual dizziness among the four groups (p > 0.005). After 3 and 5 days of treatment, the mean DHI scores of the groups receiving medication did not differ significantly from the the mean DHI score of the control group (p > 0.005). CONCLUSIONS: Our study results suggest that betahistine, trimetazidine, and gingko biloba extract do not alleviate residual dizziness after successful repositioning maneuvers.

[Pharmacological therapy of age-related macular degeneration based on etiopathogenesis]. / Adalékok az idoskori maculadegeneráció - etiopatogenezisébol fakadó - gyógyszeres intervenciójához.

It is of great therapeutic significance that disordered function of the vascular endothelium which supply the affected ocular structures plays a major role in the pathogenesis and development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfunction, and age-related macular degeneration is accompanied by a general inflammatory response. According to current concept, age-related macular degeneration is a local manifestation of systemic vascular disease. This recognition could have therapeutic implications because restoration of endothelial dysfunction can restabilize the condition of chronic vascular disease including age-related macular degeneration as well. Restoration of endothelial dysfunction by pharmaacological or non pharmacological interventions may prevent the development or improve endothelial dysfunction, which result in prevention or improvement of age related macular degeneration as well. Medicines including inhibitors of the renin-angiotensin system (converting enzyme inhibitors, angiotensin-receptor blockers and renin inhibitors), statins, acetylsalicylic acid, trimetazidin, third generation beta-blockers, peroxisome proliferator-activated receptor gamma agonists, folate, vitamin D, melatonin, advanced glycation end-product crosslink breaker alagebrium, endothelin-receptor antagonist bosentan, coenzyme Q10; "causal" antioxidant vitamins, N-acetyl-cysteine, resveratrol, L-arginine, serotonin receptor agonists, tumor necrosis factor-alpha blockers, specific inhibitor of the complement alternative pathway, curcumin and doxycyclin all have beneficial effects on endothelial dysfunction. Restoration of endothelial dysfunction can restabilize chronic vascular disease including age-related macular degeneration as well. Considering that the human vascular system is consubstantial, medicines listed above should be given to patients (1) who have no macular degeneration but have risk factors for the disease and are older than 50 years; (2) who have been diagnosed with unilateral age-related macular degeneration in order to prevent damage of the contralateral eye; (3) who have bilateral age-related macular degeneration in order to avert deterioration and in the hope of a potential improvement. However, randomised prospective clinical trials are still needed to elucidate the potential role of these drug treatments in the prevention and treatment of age-related macular degeneration.

Management of sudden hearing loss with hyperbaric oxygen therapy.

UNLABELLED: Idiopathic sudden sensorineural hearing loss (ISSHL) is defined as the sensorineural hearing loss of a minimum of 30 dB in at least three frequencies for three days or more. This study aims to evaluate the clinical efficacy of hyperbaric oxygen therapy (HBO2) in the management of idiopathic sudden sensorineural hearing loss. MATERIAL-METHODS: Patients with ISSHL received treatment including oral corticosteroids and HBO2. HBO2 protocol included five phases of five sessions each. ISSHL was assessed by measuring the tonal audiogram before and after each phase. Tinnitus was assessed using a questionnaire and a visual analogue scale at the beginning and the end of the study. Secondary assessment points included changes in the intensity and the improvement of tinnitus. RESULTS: 56 patients were included in the study. All patients completed Phases I and II of HBO2, 43 completed Phase III, 13 completed Phase IV, and six completed all five phases. Overall, a significant improvement was noted between the initial and final audiogram after HBO2 (p < 0.001). Tinnitus evaluation score, intensity and related problems were also significantly reduced (p < 0.001). CONCLUSION: This study affirms previous findings that the use of HBO2 and vasodilators are efficacious in the treatment of ISSHL. Our findings also suggest benefit for the treatment of tinnitus.

[An efficacy comparison of betahistin, trimetazidine and ginkgo biloba extract in patients with tinnitus]. / Tinnituslu hastalarda trimetazidin, betahistin ve ginkgo biloba ekstresi etkinliginin karsilastirilmasi

OBJECTIVES: This study aims to investigate the efficacy of trimetazidine, betahistine and ginkgo biloba extract in the treatment of tinnitus. PATIENTS AND METHODS: Complete clinical data of 90 patients (48 males, 42 females; mean age 52.3±15.1 years; range 20 to 61 years) who received betahistine, trimetazidine and ginkgo biloba extract for three months were retrospectively analyzed. The patients were divided into three groups including 30 in each group according to treatments received. Pre-treatment and post-treatment scores of tinnitus disability questionnaire were compared statistically. RESULTS: There was no statistically significant difference between pre-treatment scores of tinnitus disability questionnaire among all three groups (p>0.05), while there was a statistically significant difference among the groups following treatment (p=0.019, p<0.05). After a-three-month treatment, a decrease of 19.7±15.5 units in trimetazidine group, 12.2±12.7 units in betahistine group, and 3.80±5.9 units in ginkgo biloba extract group were found to be statistically significant, compared to the mean pretreatment tinnitus disability questionnaire scores (p=0.002, p<0.01). CONCLUSION: Our study results suggest that trimetazidine, betahistin and ginkgo biloba extract reduce tinnitus symptoms. However, symptomatic relief can be mostly achieved with trimetazidine treatment.

[Clinical aspects of the use of trimetazidine in the prevention and treatment of myocardial diseases]. / Kliniczne aspekty zastosowania trimetazydyny w prewencji i terapii chorób miesnia sercowego.

Trimetazidine, next to ranolazine and L-carnitine, belongs to cardioprotective drugs and as their main agent is used in experimental and clinical trials to evaluate its effect on modulation of cardiomyocytes metabolism. The blockade of fatty acid oxidation in ischemic myocardium and increase in the glucose utilization are the main mechanisms of trimetazidine action, which eventually lead to the reduction in intracellular acidosis. Recent studies concerning cardioprotective treatment encourage to continue the research on effectiveness, possible side effects, and clinical outcome which arise from "metabolic shift" toward the improvement of glucose metabolism. It has been demonstrated that trimetazidine not only ameliorate the quality of life by increasing physical tolerance, but also inhibits cardiac remodeling associated with long-standing diabetes or ischemia. Futhermore, trimetazidine exhibits antiarrhythmic properties and reduces myocardial damage associated with oxidative stress and inflammation after invasive procedures. In the light of these findings, trimetazidine seems to be an attractive therapeutic option andlor complementary therapy for treated conservatively patients with heart disease and with high risk of postreperfusal damage after cardiac invasive procedures. Moreover, particularly large benefits from introducing the metabolic treatment obtain patients with diabetes. The literature concerning trimetazidine function and treatment is broad. Therefore, the aim of this article is to summarize recent multicenter clinical trials on metabolic cardioprotection, showing its effectiveness or neutrality to the myocardial damaging factors.

Trimetazidine protects against smoking-induced left ventricular remodeling via attenuating oxidative stress, apoptosis, and inflammation.

Trimetazidine, a piperazine derivative used as an anti-anginal agent, improves myocardial glucose utilization through inhibition of fatty acid metabolism. The present study was designed to investigate whether trimetazidine has the protective effects against smoking-induced left ventricular remodeling in rats. In this study, Wistar rats were randomly divided into 3 groups: smoking group (exposed to cigarette smoke), trimetazidine group (exposed to cigarette smoke and treated with trimetazidine), and control group. The echocardiographic and morphometric data indicated that trimetazidine has protective effects against smoking-induced left ventricular remodeling. Oxidative stress was evaluated by detecting malondialdehyde, superoxide dismutase, and glutathione peroxidase in the supernatant of left ventricular tissue. Cardiomyocyte apoptotic rate was determined by flow cytometry with Annexin V/PI staining. Gene expression and serum levels of inflammatory markers, including interleukin-1ß, interleukin-6, and tumor necrosis factor-α, were deteced by quantitative real-time PCR and enzyme-linked immunosorbent assay. Our results suggested that trimetazidine could significantly reduce smoking-induced oxidative stress, apoptosis, and inflammation. In conclusion, our study demonstrates that trimetazidine protects against smoking-induced left ventricular remodeling via attenuating oxidative stress, apoptosis, and inflammation.

[Myocardial cytoprotectors, a reserve therapeutic modality for patients with stable angina of effort].

The study included 1418 patients with FC I-IV stable angina of effort (42.4% men and 57.6% women, mean age 74.6 +/- 1.2 years). The possibility to supplement standard therapy with myocardial cytoprotectors (trimetasidin, mexidol, qudesan) was estimated in 4 groups of patients from the severity of pain syndrome, chronic cardiac insufficiency, and heart rhythm disturbances.