ÖZETAmaç: Oksidatif stres, adriamisinin (ADR) neden olduğu kardiyak fonksiyon bozukluğu patogenezinde, önemli faktörlerden birisidir. Bu çalışma-da sıçanlarda 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.) sadece adriamisin (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 bir hafta önce verilmeye başlandı ve sonraki bir hafta adriamisinle birlikte verildi. Fizyolojik fonksiyon değerlendirmelerinden sonra biyokimyasal tayinler için kan örnekleri alındı. Kalpler hemodinamik çalışma için izole edildi. Gruplar arası farklılıkların belirlenmesi için ANOVA ve posthoc Tukey testi kullanıldı. Bulgular: Adriamisin, belirgin bir şekilde kalp hasarı yapmış olup; karnozin ve kontrol grubuna göre, hemodinamik değişiklikler [azalmış sol ventrikül basınç gelişimi (p<0.01), maksimum-minimum sol ventrikül basınç değişim oranları (±dP/dt, p<0.01)], elektrokardiyogram (EKG) değişik-likleri (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 ABSTRACT Objective: Oxidative stress is one of the major factors involved in the pathogenesis of adriamycin (ADR)-induced cardiac dysfunction. The present 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). Carnosine was 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 different groups 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 aminotransferase and alanine aminotransferase), plasma antioxidant enzymes activity changes (decreased superoxide dismutase, glutathione peroxidase, catalase activities, p<0.03) and lipid peroxidation (eleva...

Adriamycin (ADR) is commonly used for many solid tumor treatments. Its clinical utility is, however, largely limited by the adverse reactions, are known to be nephrotoxic. The mechanism by which it induces kidney damage is still not completely understood, but its nephrotoxicity might relate to increase reactive oxidant status (ROS), mitochondrial dysfunction. Until now, neurohormonal activation of it is unclear. ADR might activate the renin angiotensin system. Angiotensin-II also induced ROS and mitochondrial dysfunction. The aim of this study was to investigate whether angiotensin-II production inhibition has the protective effect on attenuation of mitochondrial function in rats with acute ADR-nephrotoxicity or not. Rats were divided into five groups as a control, ADR, co-treated ADR with captopril (CAP), co-treated ADR with Aliskren, co-treated ADR with both CAP and Aliskren groups. Creatinine kinase (CK) levels were measured at the end of treatment period. The kidneys were homogenized and biochemical measurements were made in mitochondria, cytosol. Mitochondria membrane potential (MMP) and ATP levels were determined. ADR increased CK levels and oxidative stress in mitochondria too (p50.05). ADR significantly decreased MMP and ATP level in kidney mitochondria (p50.05). Co-administration with ADR and Aliskren and CAP improved the dissipation of MMP (p50.05). The decrease in ATP level was restored by treatment with inhibitors of ACE and renin. We concluded that inhibitors of angiotensin-II are effective against acute ADR induced nephrotoxicity via the restoration of MMP and ATP production and prevention of mitochondrial damage in vivo. KeywordsAdriamycin-induced nephrotoxicity, Aliskren, captopril, mitochondrial ATP, mitochondrial membrane potential, oxidative stress index History

Adriamycin (ADR) increases the production of reactive oxygen species (ROS), 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 protect against ADR-induced mitochondrial function impairment. Rats were divided into five groups as control, ADR, co-treatment ADR with captopril, co-treatment ADR with aliskiren, co-treatment ADR with both captopril and aliskiren. Left ventricular function and blood pressures were assessed at the end of treatment period. Mitochondrial membrane potential (MMP) and ATP levels were determined. ADR treatment decreased the left ventricular pressure and increased the left ventricular end-diastolic pressure. ADR decreased MMP and ATP levels in myocyte mitochondria due to increasing oxidative stress. ADR decreased MMP and ATP levels due to increased oxidative stress in the heart. Inhibitors of ACE and renin caused the elevation of the decreased of MMP and ATP levels. The pathologic changes in electrocardiogram, blood pressure and left ventricular function were decreased by inhibition of Ang-II production. 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.

ÖZETObjective: The aim of this study was to determine whether regular physical activity or acute exercise influenced plasma adrenomedullin (AM) concentration and whether it was related to gender, blood pressure and nitric oxide (NO) production. Material and Methods:Sixty healthy students participated in this study. They were divided into two groups. The first group consisted of 30 students, 16 female, 14 male athletes carrying out regular exercise. The second group was made up of 15 females, 15 males nonathletes. All students submitted to a cycle exercise test until volitional exhaustion. Heart rate (HR), blood pressure, maximal oxygen uptake (VO 2 max) and carbon dioxide production (VCO 2 ) were measured continously. Before starting, at the 1 st min and at the 30 th min of exercise, venous blood samples were taken to determine AM and NO production.Results: AM in the female and male athletes were significantly higher than in the female and male non-athletes. The plasma AM concentration in female athletes was found be significantly higher than in male athletes. Acute exercise did not affect AM concentration in subjects. We did not find any relationship between AM/BMI (Body mass index) and other variables such as systolic, diastolic pressure, heart rate, VO 2 max and VCO 2 but there was a negative relationship with NO production. Conclusion:The present data suggest that an increase in AM during prolonged physical activity may be a compensatory mechanism against further elevation of blood pressure.

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 cotreated 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 (þdP/dt), and increased in the left ventricular enddiastolic 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.

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