Effects of Carnosine on the Toxicity of Doxorubicin in Rabbits and Mice

Zieba, Remigiusz; Czarnecka, E; Wągrowska-Danilewicz, Małgorzata; Dzielska-Olczak, Małgorzata; Graczyk, J

doi:10.1515/pteridines.2003.14.3.94

Cited by 9 publications

(8 citation statements)

References 30 publications

(16 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Its levels in the body decline 63% from age 10 years to age 70 years (). Considerable evidence indicates that it has protective properties in several diseases, including atherosclerosis (), cardiomyopathy (), and osteoporosis (). To date, there are no reported studies concerning the in vivo beneficial effects of carnosine in OA.…”

Section: Discussionmentioning

confidence: 99%

New Evidence Implicating 4‐Hydroxynonenal in the Pathogenesis of Osteoarthritis In Vivo

Shi

Abusarah

Zaouter

et al. 2014

Arthritis & Rheumatology

View full text Add to dashboard Cite

Objective. To demonstrate the involvement of 4-hydroxynonenal (HNE), a very reactive aldehyde derived from lipid peroxidation, in the pathogenesis of osteoarthritis (OA) in vivo.Methods. In the first experimental protocol, OA was induced by anterior cruciate ligament transection (ACLT) of the right knees of crossbred dogs (n ‫؍‬ 6 per group). The animals were treated with placebo or HNEtrapping carnosine (5 or 20 mg/kg/day) orally for 8 weeks. Another group of dogs was treated for 4 weeks with 20 mg/kg/day of carnosine starting 4 weeks after surgery. Sham-operated dogs served as controls. In the second experimental protocol, a pathophysiologic dose of HNE (80 nmoles/ml) or vehicle was injected weekly into the right knee joints of crossbred dogs (n ‫؍‬ 6 per group) for 8 weeks. Articular cartilage was subjected to macroscopic, histomorphologic, and immunohistochemical analyses. Cartilage-degrading enzymes and oxidative stress-related products were assessed in synovial fluid and cartilage explants. Markers of inflammation were evaluated in synovium and synovial fluid.Results. In dogs that had undergone ACLT, carnosine treatment reduced the severity and histopathology score of OA cartilage lesions and also decreased HNE-protein adducts, pentosidine, nitrosylated proteins, cartilage-degrading enzymes, and markers of inflammation. Intraarticular injection of HNE induced cartilage lesions, as assessed by macroscopic and microscopic criteria. Cartilage-degrading enzymes and markers of inflammation increased in HNE-treated dogs.Conclusion. This is the first in vivo study to demonstrate the pathophysiologic role of HNE in OA. That carnosine abolishes HNE production and a number of factors known to be involved in OA pathogenesis renders it a clinically valuable agent in prevention of the disease.

show abstract

Section: Discussionmentioning

confidence: 99%

New Evidence Implicating 4‐Hydroxynonenal in the Pathogenesis of Osteoarthritis In Vivo

Shi

Abusarah

Zaouter

et al. 2014

Arthritis & Rheumatology

View full text Add to dashboard Cite

show abstract

“…Two studies determined the protective effect of carnosine (CAR) on the cardiotoxicity of adriamycin (ADR) (7,8). These studies evaluated the influences of adriamycin on the hemodynamic parameters and on the degree of cardiac muscle cell alterations.…”

Section: Introductionmentioning

confidence: 99%

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

Özdoğan¹,

Taşkın²,

Dursun³

2011

Anadolu Kardiyol Derg

View full text Add to dashboard Cite

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...

show abstract

“…Carnosine attenuated microglia activation and cortical neuron apoptosis in a rat model of experimental subarachnoid hemorrhage [107]. Co-administration of carnosine with doxorubicin normalized blood pressure, improved cardiac and stroke indices, and reduced cardiac muscle damage in rabbits with doxorubicin-induced congestive heart failure [108]. …”

Section: Reactive Carbonyl Species Scavengers Ameliorate Diseasementioning

confidence: 99%

Reactive Carbonyl Species Scavengers—Novel Therapeutic Approaches for Chronic Diseases

Davies

Zhang

2017

Curr Pharmacol Rep

View full text Add to dashboard Cite

Purpose of the review To summarize recent evidence supporting the use of reactive carbonyl species scavengers in the prevention and treatment of disease. Recent findings The newly developed 2-aminomethylphenol class of scavengers shows great promise in preclinical trials for a number of diverse conditions including neurodegenerative diseases and cardiovascular disease. In addition, new studies with the thiol-based and imidazole-based scavengers have found new applications outside of adjunctive therapy for chemotherapeutics. Summary Reactive oxygen species (ROS) generated by cells and tissues act as signaling molecules and as cytotoxic agents to defend against pathogens, but ROS also cause collateral damage to vital cellular components. The polyunsaturated fatty acyl chains of phospholipids in the cell membranes are particularly vulnerable to damaging peroxidation by ROS. Evidence suggests that the breakdown of these peroxidized lipids to reactive carbonyls species plays a critical role in many chronic diseases. Antioxidants that abrogate ROS-induced formation of reactive carbonyl species also abrogate normal ROS signaling and thus exert both beneficial and adverse functional effects. The use of scavengers of reactive dicarbonyl species represent an alternative therapeutic strategy to potentially mitigate the adverse effects of ROS without abrogating normal signaling by ROS. In this review, we focus on three classes of reactive carbonyl species scavengers: thiol-based scavengers (2-mercaptoethanesulfonate and amifostine), imidazole-based scavengers (carnosine and its analogs), and 2-aminomethylphenols-based scavengers (pyridoxamine, 2-hydroxybenzylamine, and 5’-O-pentyl-pyridoxamine) that are either undergoing pre-clinical studies, advancing to clinical trials, or are already in clinical use.

show abstract

Effects of Carnosine on the Toxicity of Doxorubicin in Rabbits and Mice

Cited by 9 publications

References 30 publications

New Evidence Implicating 4‐Hydroxynonenal in the Pathogenesis of Osteoarthritis In Vivo

New Evidence Implicating 4‐Hydroxynonenal in the Pathogenesis of Osteoarthritis In Vivo

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

Reactive Carbonyl Species Scavengers—Novel Therapeutic Approaches for Chronic Diseases

Contact Info

Product

Resources

About