Tannic acid ameliorates arsenic trioxide-induced nephrotoxicity, contribution of NF-κB and Nrf2 pathways

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arsenic trioxide (aTo) is commonly used to treat patients with acute promyelocytic leukemia since it was authorized by the u.S. Food and drug administration in the 1970s, but its applicability has been limited by its cardiotoxic effects. Therefore, the aim of the present study was to investigate the cardioprotective effects and underlying mechanism of crocetin (crT), the critical ingredient of saffron. Sprague-dawley rats were then randomly divided into four groups (n=10/group): i) control group; ii) aTo group, iii) crT-low (20 mg/kg) group; and iv) crT-high (40 mg/kg) group. rats in the control and aTo groups were intraperitoneally injected with equal volumes of 0.9% sodium chloride solution, and crT groups were administered with either 20 and 40 mg/kg crT. Following 6 h, all groups except the control group were intraperitoneally injected with 5 mg/kg aTo over 10 days. cardiotoxicity was indicated by changes in electrocardiographic (ecG) patterns, morphology and marker enzymes. Histomorphological changes in the heart tissue were observed by pathological staining. The levels of superoxide dismutase, glutathione peroxidase, malondialdehyde and catalase in the serum were analyzed using colometric commercial assay kits, and the levels of reactive oxygen species in the heart tissue were detected using the fluorescent probe dihydroethidium. The expression levels of inflammatory factors and activities of apoptosis-related proteins were analyzed using immunohistochemistry. The protein expression levels of silent information regulator of transcription 1 were measured using western blotting. cardiotoxicity was induced in male Sprague-dawley rats with aTo (5 mg/kg). crT (20 and 40 mg/kg) and aTo were co-administered to evaluate possible cardioprotective effects. CRT significantly reduced the heart rate and J-point elevation induced by aTo in rats. Histological changes were evaluated via hematoxylin and eosin staining. crT decreased the levels of creatine kinase and lactate dehydrogenase, increased the activities of superoxide dismutase, glutathione-peroxidase and catalase, and decreased the levels of malondialdehyde and reactive oxygen species. Moreover, crT downregulated the expression levels of the pro-inflammatory factors IL-1, TnF-α, il-6, Bax and p65, as well as increased the expression of Bcl-2. It was also identified that CRT enhanced silent information regulator of transcription 1 protein expression. Thus, the present study demonstrated that crT treatment effectively ameliorated aTo-induced cardiotoxicity. The protective effects of crT can be attributed to the inhibition of oxidative stress, inflammation and apoptosis. Therefore, CRT represents a promising therapeutic method for improving the cardiotoxic side effects caused by aTo treatment, and additional clinical applications are possible, but warrant further investigation.

Section: Detection Of Rosmentioning

confidence: 99%

“…Membranes were washed three times and proteins were visualized using the ecl detection system (TransGen Biotech co., ltd.) (53), and imaged using Tanon-1600 Gel image analysis system (Tanon Science and Technology co., ltd.). Bands were quantified using Tanon Gis 1D software (Tanon Science and Technology co., ltd.) (49).…”

Section: Detection Of Catalase (Cat)mentioning

confidence: 99%

Ameliorative effects and mechanism of crocetin in arsenic trioxide‑induced cardiotoxicity in rats

Zhao

Zheng

et al. 2020

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“…Our previous studies have indicated that TA has beneficial effects on cardiovascular disease (42)(43)(44); moreover, we found that Ta ameliorates aTo-induced nephrotoxicity (45). However, the effects of Ta on aTo-induced cardiotoxicity have not yet been reported.…”

Section: Introductionmentioning

confidence: 78%

“…The control group received isovolumic normal saline. The aTo + l-Ta and aTo + H-Ta groups underwent intragastric administration of Ta (20 and 40 mg/kg/day, respectively) every morning and were intraperitoneally injected with aTo (5 mg/kg/day) every afternoon (40,42,45). after 7 days, sodium pentobarbital (40 mg/kg, i.p.…”

Section: Methodsmentioning

confidence: 99%

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

Xue

et al. 2020

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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.

“…An increasing number of studies have consistently shown that ATO is effective against other cancer types, including hepatocellular carcinoma, pancreatic cancer and lung cancer (9,10). In past decades, clinical data have shown that excessive use of ATO causes hepatotoxicity, nephrotoxicity and cardiotoxicity (11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Exploration of the hepatoprotective effect and mechanism of magnesium isoglycyrrhizinate in mice with arsenic trioxide‑induced acute liver injury

Liu

Zheng

et al. 2021

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Arsenic trioxide (ATO)-induced hepatotoxicity limits the therapeutic effect of acute myelogenous leukemia treatment. Magnesium isoglycyrrhizinate (MgIG) is a natural compound extracted from licorice and a hepatoprotective drug used in liver injury. It exhibits anti-oxidant, anti-inflammatory and anti-apoptotic properties. The aim of the present study was to identify the protective action and underlying mechanism of MgIG against ATO-induced hepatotoxicity. A total of 50 mice were randomly divided into five groups (n=10/group): Control; ATO; MgIG and high-and low-dose MgIG + ATO. Following continuous administration of ATO for 7 days, the relative weight of the liver, liver enzyme, histological data, antioxidant enzymes, pro-inflammatory cytokines, cell apoptosis and changes in Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) signaling pathway were observed. MgIG decreased liver injury, decreased the liver weight and liver index, inhibited oxidative stress and decreased the activity of glutathione, superoxide dismutase and catalase, production of reactive oxygen species and levels of pro-inflammatory cytokines, including IL-1β, IL-6 and TNF-α. Western blotting showed a decrease in Bax and caspase-3. There was decreased cleaved caspase-3 expression and increased Bcl-2 expression. MgIG notably activated ATO-mediated expression of Keap1 and Nrf2 in liver tissue. MgIG administration was an effective treatment to protect the liver from ATO-induced toxicity. MgIG maintained the level of Nrf2 in the liver and protected the antioxidative defense system to attenuate oxidative stress and prevent ATO-induced liver injury.