Protective effect of carnosine on adriamycin-induced oxidative heart damage in rats

Amaç: Oksidatif stres, adriamisinin (ADR) neden olduğu kardiyak fonksiyon bozukluğu patogenezinde, önemli faktörlerden birisidir. Bu çalışmadasıçanlarda adriamisin ile oluşturulan kalp hasarı üzerine karnozinin antioksidan savunma etkisi araştırılmıştır.Yöntemler: Dişi Spraque Dawley sıçanlar 4 gruba ayrıldı; kontrol (KONT, n=8, serum fizyolojik i.v.); karnozin (KAR, n=8, 10 mg/kg/gün, i.v.) sadeceadriamisin (ADR, n=10, 4 mg/kg dört defa, iki gün ara ile toplam 8 gün, i.v.); karnozin ile adriamisin (KAR+ADR, n=10). Karnozin, adriamisinden birhafta önce verilmeye başlandı ve sonraki bir hafta adriamisinle birlikte verildi. Fizyolojik fonksiyon değerlendirmelerinden sonra biyokimyasaltayinler için kan örnekleri alındı. Kalpler hemodinamik çalışma için izole edildi. Gruplar arası farklılıkların belirlenmesi için ANOVA ve posthocTukey testi kullanıldı.Bulgular: Adriamisin, belirgin bir şekilde kalp hasarı yapmış olup; karnozin ve kontrol grubuna göre, hemodinamik değişiklikler [azalmış solventrikül basınç gelişimi (p<0.01), maksimum-minimum sol ventrikül basınç değişim oranları (±dP/dt, p<0.01)], elektrokardiyogram (EKG) değişiklikleri(artmış ST ve azalmış R-dalgası, p<0.001), kardiyak hasar belirleyicilerindeki değişiklikler (artmış kreatin kinaz, laktat dehidrogenaz,aspartat aminotransferaz, alanin aminotransferaz), plazma antioksidan aktivite değişiklikleri (azalmış süperoksit dismutaz, glutatyon peroksidaz,katalaz aktiviteleri, p<0.03) ve lipit peroksidasyonuna (artmış malondialdehit, p<0.05) neden olmuştur. Karnozin tedavisi (KAR+ADR); ventriküler fonksiyon, EKG ve biyokimyasal değişkenleri normal değerlerine yaklaştırarak, adriamisinin neden olduğu kardiyak fonksiyon bozukluklarınınönemli derecede azalmasına sebep olmuştur.Sonuç: Adriamisinin oksidatif streste yaptığı artış, süperoksit dismutaz, glutatyon peroksidaz, katalaz gibi antioksidan enzim aktivasyon baskılayıcıetkileri ile oluşan kalp fonksiyon bozuklukları, karnozin ile engellenmiştir. (Anadolu Kardiyol Derg 2011 1: 3-10)Anahtar kelimeler: Adriamisin, karnozin, kalp hasarı, Langendorff, antioksidanObjective: Oxidative stress is one of the major factors involved in the pathogenesis of adriamycin (ADR)-induced cardiac dysfunction. Thepresent study examined the antioxidant protective effects of carnosine (CAR) on adriamycin-induced cardiac damage in rats.Methods: Female Sprague Dawley rats were divided into four groups. Control (CONT, n=8, saline only i.v.); carnosine (CAR, n=8.10 mg/kg/day,i.v.); adriamycin (ADR, n=10.4 mg/kg four times every 2 days for 8 days, i.v.) alone and carnosine with adriamycin (CAR+ADR, n=10). Carnosinewas given one week before adriamycin treatment and following one week with adriamycin treatment. After measurement of physiological functions,blood samples were collected for biochemical assays. The hearts were excised for hemodynamic study. Comparisons between differentgroups were made using ANOVA and posthoc Tukey test.Results: Adriamycin produced evident cardiac damage revealed by; hemodynamic changes - decreased left ventricular developed pressure(p<0.01), the maximum-minimum rates of change in left ventricular pressure (±dP/dt, p<0.01), electrocardiogram (ECG) changes (elevated ST,decreased R-wave, p<0.001), cardiac injury marker changes (increased creatine kinase, lactate dehydrogenase, aspartate aminotransferaseand alanine aminotransferase), plasma antioxidant enzymes activity changes (decreased superoxide dismutase, glutathione peroxidase, catalaseactivities, p<0.03) and lipid peroxidation (elevated malondialdehyde, p<0.05) to the control and carnosine groups. Carnosine treatmentcaused significant attenuation (p<0.05) of cardiac dysfunction induced by adriamycin (CAR+ADR), revealed by normalization of the ventricularfunction, ECG and biochemical variables.Conclusion: An increase in oxidative stress, superoxide dismutase, glutathione peroxidase levels, catalase inactivation and cardiac dysfunctioninduced by adriamycin were prevented by carnosine. (Anadolu Kardiyol Derg 2011 1: 3-10)Key words: Adriamycin, carnosine, cardiac damage, Langendorff, antioxidan

The Potential Anti-Diabetic Effects of Some Plant Species

Diabetes mellitus is a global disease, of which prevalence increases rapidly. It causes severe microvascular and macrovascular complications such as retinopathy, nephropathy, cardiomyopathy, neuropathy etc. These contribute to morbidity and mortality in diabetic patients. Therefore, it is important to find an effective therapy method(s) for the protection of body from diabetes-related complications. In this sense, herbal products are of great importance. Herein, this review will highlight the potential usage of some herbals as a preventive and/or therapeutic approach in diabetes and discusses the possible underlying mechanisms of anti-diabetic actions

THE ROLE OF ANGIOTENSIN ON MITOCHONDRIAL ATP PRODUCTION AND THE EFFECT OF ANGIOTENSIN ON ADRIAMYCIN-INDUCED CARDIOMYOPATHY

Background: Adriamycin increases reactive oxygen species and this leads to diminish mitochondrial function. Angiotensin-II stimulates mitochondrial-ROS generation. It was aimed to examine whether the diminishing mitochondrial energy production induced by ADR is attenuated by rennin-angiotensin inhibitors. Methods: Rats were divided into five groups. The control group was treated with normal saline. Adriamycin was administered to the second group at a dose of 4 mg/kg i.p every other 2 days. Captopril were administered to the third group at a dose 10 mg/kg plus ADR. Aliskiren was administered to the fourth group at a dose 50 mg/kg plus ADR. Captopril, Aliskiren and ADR were administered to the last group at the same dose. Captopril and aliskiren were gavage administration daily for 8 times. Left ventricular functions, ECG variables and blood pressure were assessed at the end of injection period. Mitochondrial ATP levels were determined. Results: Only ADR treated animals had a decrease in the left ventricular developed pressure, a decrease in the maximal rate of the increased pressure, and an increase in the left ventricular end-diastolic pressure. ADR increased ST interval and decreased mean blood pressure. ADR decreased ATP level in myocyte mitochondria. By maintaining normal levels of mitochondrial ATP, captopril and aliskiren treatment prevented the changes in ECG, blood pressure and left ventricular function.Conclusions: We concluded that inhibitors of ACE and renin could be effective against ADR cardiotoxicity via the restoration of ATP production and prevention of mitochondrial damage in vivo.Key words: Adriamycin, Mitochondrial AT

Adriamycin-Induced Mitochondrial Toxicity in Rat Heart is Exacerbate by Angiotensin

Adriamycin (ADR) increases the production of reactive oxygen species, which diminishes mitochondrial function. Angiotensin-II stimulates mitochondrial-ROS generation. The aim of the study was to examine whether angiotensin converting enzyme (ACE) or renin inhibitors (captopril and/or aliskiren) protect against ADR-induced mitochondrial function impairment.Rats were divided into five groups (n=14 each). The control group was treated with saline. ADR was administered to the four other groups every 2 days (4 mg/kg i.p). One of these was co-administered captopril (10 mg/kg/daily) and the other was co-treated with aliskiren (50 mg/kg/daily), while another was co-treated with both captopril and aliskiren (captopril and aliskiren were gavage administration daily for 8 days). Left ventricular function, ECG variables and blood pressure were assessed at the end of treatment period. The hearts were homogenized and biochemical measurements were made in mitochondria, cytosol and plasma. Mitochondria membrane potential (MMP), ATP levels were determined.ADR decreased in the left ventricular developed pressure (LVDP), the maximal rate of rise of pressure (+dP/dt), and increased in the left ventricular end-diastolic pressure (LVEDP). ADR increased ST interval and decreased mean blood pressure. ADR increased oxidative stress in mitochondrial, cytosolic and plasma. ADR decreased MMP and ATP level in myocyte mitochondria. ADR co-administration with renin and ACE inhibitors improved the dissipation of MMP. The decreased in ATP level was restored by treatment with inhibitors of ACE and renin. By maintaining normal levels of mitochondrial MMP and ATP, captopril and aliskiren treatment prevented the pathologic changes in ECG, blood pressure and left ventricular function.We concluded that inhibitors of angiotensin II are effective against ADR cardiotoxicity via the restoration of MMP and ATP production and prevention of mitochondrial damage in vivo.</p