tannins and Cardiotoxicity

Arsenic trioxide (ATO) is a frontline chemotherapy drug used in the therapy of acute promyelocytic leukemia. However, the clinical use of ATO is hindered by its cardiotoxicity. The present study aimed to observe the potential effects and underlying mechanisms of tannic acid (TA) against ATO‑induced cardiotoxicity. Male rats were intraperitoneally injected with ATO (5 mg/kg/day) to induce cardiotoxicity. TA (20 and 40 mg/kg/day) was administered to evaluate its cardioprotective efficacy against ATO‑induced heart injury in rats. Administration of ATO resulted in pathological damage in the heart and increased oxidative stress as well as levels of serum cardiac biomarkers creatine kinase and lactate dehydrogenase and the inflammatory marker NF‑κB (p65). Conversely, TA markedly reversed this phenomenon. Additionally, TA treatment caused a notable decrease in the expression levels of cleaved caspase‑3/caspase‑3, Bax, p53 and Bad, while increasing Bcl‑2 expression levels. Notably, the application of TA decreased the expression levels of cytochrome c, second mitochondria‑derived activator of caspases and high‑temperature requirement A2, which are apoptosis mitochondrial‑associated proteins. The present findings indicated that TA protected against ATO‑induced cardiotoxicity, which may be associated with oxidative stress, inflammation and mitochondrial apoptosis.

Topics: Animals; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; Arsenic Trioxide; Cardiotoxicity; Caspases; Inflammation; Male; Mitochondria; Myocardium; Myocytes, Cardiac; Oxidative Stress; Oxides; Rats; Rats, Sprague-Dawley; Tannins

Doxorubicin (DOX) is a highly effective drug, but its cardiotoxicity restricts its therapeutic index. Oxidative stress is the major etiopathological factor in DOX-induced cardiotoxicity. Tannic acid (TA) has various anti-cancer, antioxidant, and anti-inflammatory activities. The purpose of the study was to survey the possible effects of TA against acute DOX-induced cardiotoxicity. Male Sprague-Dawleyrats were randomly divided into five groups: control, DOX (10mg/kg) alone, DOX with TA (20 and 40mg/kg), or DOX withcaptopril (30mg/kg) treatments. TA or captopril was administered once daily for six days, and DOX was injected intraperitoneally on the fourth day. TA significantlyattenuated DOX myocardial effects. Pretreatment with TA caused a decrease in levels of the serum enzymes lactate dehydrogenase, creatine kinase, and creatine kinase isoenzyme-MB to normal values. As indicators of oxidative stress, the levels of glutathione peroxidasesuperoxide dismutase and catalasesignificantly increased while the levels of malondialdehyde decreased after TA treatment. Additionally, DOX provoked inflammatory responses by causing anincrease in levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), endothelin (ET)-1 levels, and nuclear factor kappa-B (NF-κB) expression while TA pretreatment significantly inhibited TNF-α, IL-1β, ET-1, and NF-κB. Furthermore, DOX induced apoptosis by increasing bcl-2like protein and caspase-3 activities and c-fos and c-jun levels while causing a decrease in B-cell lymphoma-2 levels. Overall, there was evidence that TA could inhibit DOX-induced cardiotoxicity by inhibiting oxidative stress, inflammation and apoptotic damage.

Topics: Animals; Antibiotics, Antineoplastic; Antioxidants; Apoptosis; Cardiotoxicity; Caspase 3; Cytokines; Doxorubicin; Glutathione; Inflammation; Interleukin-1beta; Male; Malondialdehyde; Myocardium; NF-kappa B; Oxidative Stress; Protective Agents; Rats; Rats, Sprague-Dawley; Tannins; Tumor Necrosis Factor-alpha