Mechanisms underlying the protective effect of tannic acid against arsenic trioxide‑induced cardiotoxicity in rats: Potential involvement of mitochondrial apoptosis

Abstract

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.

Based on Activation of p62-Keap1-Nrf2 Pathway, Hesperidin Protects Arsenic-Trioxide-Induced Cardiotoxicity in Mice

“…Recent studies have demonstrated that oxidative stress injury, inflammation and apoptosis of myocardial cells are potential mechanisms associated with ATO-induced cardiotoxicity, in which oxidative stress is the main cause (Chang et al, 2007;Das et al, 2010;Ye et al, 2010;Birari et al, 2020;Xue et al, 2020). Reactive oxygen species (ROS) are produced through a series of extracellular and intracellular activities, considered as a novel signalling mediator involved in cell growth, differentiation, progression and death (Sena and Chandel, 2012;Zhang et al, 2013a).…”

Mitochondrial Homeostasis and Mast Cells in Experimental Hepatic Ischemia-Reperfusion Injury of Rats

“…Although many different oxidative damage products have been identified, 8-OHdG is an important marker defined many years ago in DNA damage. 27 Therefore, in our study, 8-OhDG expression was immunohistochemically and immunofluorescent examined in terms of DNA damage, but no difference was found between the I/R group and the groups treated with uridine in terms of 8-OHDG expression. This situation is attributed to the shortness of the I/R time or the role of a different I/R-induced oxidative stress pathway.…”

Neuroprotective effects of tannic acid in the postischemic brain via direct chelation of Zn2+

“…Ashafaq et al have suggested the neuroprotective effects of TA in the MCAO model; however, detailed mechanisms explaining TA-mediated inhibition of inflammation or oxidative stress are lacking. A protective mechanism of TA by inhibiting NF-κB has been previously suggested in nephrotoxicity and cardiotoxicity (Jin et al, 2020 ; Xue et al 2020 ); however, the TA mechanism underlying these effects remains unclear. We speculated that the neuroprotective effects of TA were mainly derived from its chelating effect, given that TA is a water-soluble polyphenol with an 8 gallic acid group and acts as a metal chelator (Strlic et al 2002 ).…”