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

Cardioprotective effects of Na+/H+ exchanger inhibition on reperfusion injury in rats

WOS: 000379514000083

The restoration of kidney mitochondria function by inhibition of angiotensin-II production in rats with acute adriamycin-induced nephrotoxicity

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 (p<0.05). ADR significantly decreased MMP and ATP level in kidney mitochondria (p<0.05). Co-administration with ADR and Aliskren and CAP improved the dissipation of MMP (p<0.05). 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

Acute adriamycin-induced cardiotoxicity is exacerbated by angiotension II

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.Abstract 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 MMPand 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.&nbsp;</div