Effects of caffeic acid on doxorubicin induced cardiotoxicity in rats

2013 ◽  
Vol 2 (1) ◽  
pp. 23-27
Author(s):  
Bassim Mohammad ◽  
Nada Aharis ◽  
Maitham Yousif ◽  
Zainab Alkefae ◽  
Najah Hadi

Doxorubicin (Dox) is one of the most potent broad-spectrum antitumor anthracycline antibiotics, its use is limited by the development of life-threatening cardiomyopathy. Doxorubicin generates free radicals and induces oxidative stress associated with cellular injury. Further, it has been shown that free radicals are involved in doxorubicin-induced toxicity. The goal of this study is to investigated the cardio-protective effects of caffeic acid on doxorubicin induced cardiotoxicity. The rats were randomized into three equal groups, sham group without treatment, doxorubicin treated group at a dose 3mg/kg IP every other two days and group treated with doxorubicin plus caffeic acid 40mg/day. Two weeks later LV function measurment were performed and blood samples were collected from the heart to measurment plasma levels of cardiac Troponin-I (cTn-I), oxidative stress parameter malondialdehyde (MDA) and high a sensitive c-reactive protein (hs-CRP). The hearts were excised for cardiac tissue cytokines (TNF-α, IL-1β, IL-10) measurement and microscopic examination. Rats in the Dox+caffeic acid group had improved LV function, reduced cytokine expression, decreased myocardial marker injury (cTn-I) and less MDA, hs-CRP levels in comparison with the Dox group. Pathological finding appeared nearly normal in the Dox+caffeic acid without fibrosis. The results of the present study reveal that caffeic acid has a promising cardioprotective effect against doxorubicin-induced cardiotoxicity.

2013 ◽  
Vol 2 (1) ◽  
pp. 49-57
Author(s):  
Jens Boldron ◽  
Simon Caltabiano ◽  
Steven Debono ◽  
Robert Thompson ◽  
Malcolm Scammells ◽  
...  

Doxorubicin (Dox) is one of the most potent broad-spectrum antitumor anthracycline antibiotics, its use is limited by the development of life-threatening cardiomyopathy. Doxorubicin generates free radicals and induces oxidative stress associated with cellular injury. Further, it has been shown that free radicals are involved in doxorubicin-induced toxicity. The goal of this study is to investigated the cardio-protective effects of caffeic acid on doxorubicin induced cardiotoxicity. The rats were randomized into three equal groups, sham group without treatment, doxorubicin treated group at a dose 3mg/kg IP every other two days and group treated with doxorubicin plus caffeic acid 40mg/day. Two weeks later LV function measurment were performed and blood samples were collected from the heart to measurment plasma levels of cardiac Troponin-I (cTn-I), oxidative stress parameter malondialdehyde (MDA) and high a sensitive c-reactive protein (hs-CRP). The hearts were excised for cardiac tissue cytokines (TNF-α, IL-1β, IL-10) measurement and microscopic examination. Rats in the Dox+caffeic acid group had improved LV function, reduced cytokine expression, decreased myocardial marker injury (cTn-I) and less MDA, hs-CRP levels in comparison with the Dox group. Pathological finding appeared nearly normal in the Dox+caffeic acid without fibrosis. The results of the present study reveal that caffeic acid has a promising cardioprotective effect against doxorubicin-induced cardiotoxicity.


2019 ◽  
Vol 47 (10) ◽  
pp. 5229-5238
Author(s):  
Guo-dong Chen ◽  
Heng Fan ◽  
Jian-Hua Zhu

Objective To explore the protective effects and mechanisms of salidroside on myocardial injury induced by heat stroke (HS) in mice. Methods We pretreated mice with salidroside for 1 week and then established an HS model by exposure to 41.2°C for 1 hour. We then examined the effects of salidroside on survival. We also assessed the severity of cardiac injury by pathology, and analyzed changes in levels of myocardial injury markers, inflammatory cytokines, and oxidative stress. Results Salidroside pretreatment significantly reduced HS-induced mortality and improved thermoregulatory function. Salidroside also provided significant protection against HS-induced myocardial damage, and decreased the expression levels of cardiac troponin I, creatine kinase-MB, and lactate dehydrogenase. Moreover, salidroside attenuated HS-induced changes in the inflammation markers tumor necrosis factor-α, interleukin (IL)-6, and IL-10, and down-regulated the oxidative stress response indicated by thiobarbituric acid reactant substances, malondialdehyde, reduced glutathione, and superoxide dismutase. Conclusions Salidroside pretreatment protected against HS-induced myocardial damage, potentially via a mechanism involving anti-inflammatory and anti-oxidative effects.


2006 ◽  
Vol 8 (2) ◽  
pp. 189-193 ◽  
Author(s):  
Huseyin Ozyurt ◽  
Hidir Pekmez ◽  
Bekir Suha Parlaktas ◽  
Ilter Kus ◽  
Birsen Ozyurt ◽  
...  

Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 159
Author(s):  
Abeer M. Alanazi ◽  
Laila Fadda ◽  
Ahlam Alhusaini ◽  
Rehab Ahmad ◽  
Iman H. Hasan ◽  
...  

Doxorubicin (DOX) is a cytotoxic anthracycline antibiotic and one of the important chemotherapeutic agents for different types of cancers. DOX treatment is associated with adverse effects, particularly cardiac dysfunction. This study examined the cardioprotective effects of carvedilol (CAR) and/or resveratrol (RES) and liposomal RES (LIPO-RES) against DOX-induced cardiomyopathy, pointing to their modulatory effect on oxidative stress, inflammation, S100A1 and sarco/endoplasmic reticulum calcium ATPase2a (SERCA2a). Rats received CAR (30 mg/kg) and/or RES (20 mg/kg) or LIPO-RES (20 mg/kg) for 6 weeks and were challenged with DOX (2 mg/kg) twice per week from week 2 to week 6. DOX-administered rats exhibited a significant increase in serum creatine kinase-MB (CK-MB), troponin-I and lactate dehydrogenase (LDH) along with histological alterations, reflecting cardiac cell injury. Cardiac toll-like receptor 4 (TLR-4), inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α and interleukin (IL)-6 protein expression were up-regulated, and lipid peroxidation was increased in DOX-administered rats. Treatment with CAR, RES or LIPO-RES as well as their alternative combinations ameliorated all observed biochemical and histological alterations with the most potent effect exerted by CAR/LIPO-RES. All treatments increased cardiac antioxidants, and the expression of S100A1 and SERCA2a. In conclusion, the present study conferred new evidence on the protective effects of CAR and its combination with either RES or LIPO-RES on DOX-induced inflammation, oxidative stress and calcium dysregulation.


2017 ◽  
Vol 44 (1) ◽  
pp. 279-292 ◽  
Author(s):  
Fan Deng ◽  
Shuang Wang ◽  
Liangqing Zhang ◽  
Xiang Xie ◽  
Shuyun Cai ◽  
...  

Background/Aims: Hearts from diabetic subjects are susceptible to myocardial ischemia reperfusion (I/R) injury. Propofol has been shown to protect against myocardial I/R injury due to its antioxidant properties while the underlying mechanism remained incompletely understood. Thus, this study aimed to determine whether or not propofol could attenuate myocardial I/R injury by attenuating mitochondrial dysfunction/damage through upregulating Caveolin (Cav)-3 under hyperglycemia. Methods: Cultured rat cardiomyocyte H9C2 cells were subjected to hypoxia/reoxygenation (H/R) in the absence or presence of propofol under high glucose (HG), and cell viability, lactate dehydrogenase (LDH) and mitochondrial viability as well as creatine kinase-MB (CK-MB), cardiac troponin I (cTnI) and intracellular adenosine triphosphate (ATP) content were measured with colorimetric Enzyme-Linked Immunosorbent Assays. Intracellular levels of oxidative stress was assessed using 2,7-dichlorodihydrofluorescein diacetate (DCF-DA) fluorescent staining and mitochondrial-dependent apoptosis was assessed by detecting mitochondrial membrane potential and the activation of apoptotic caspases 3 and 9. Results: Exposure of cells to HG without or with H/R both significantly increased cell injury, cell apoptosis and enhanced oxidative stress that were associated with mitochondrial dysfunction and decreased Cav-3 protein expression. All these changes were further exacerbated following H/R under HG. Administration of propofol at concentrations from 12.5 to 50 µM but not 100 µM significantly attenuated H/R injury that was associated with increased Cav-3 expression and activation of the prosurvival proteins Akt and STAT3 with the optimal protective effects seen at 50 µM of propofol (P25). The beneficial effects of propofol(P25) were abrogated by Cav-3 disruption with β-methyl-cyclodextrin. Conclusion: Propofol counteracts cardiomyocyte H/R injury by attenuating mitochondrial damage and improving mitochondrial biogenesis through upregulating Cav-3 during hyperglycemia.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Mona A. Hussain ◽  
Noha M. Abogresha ◽  
Ghada AbdelKader ◽  
Ranya Hassan ◽  
Eman Z. Abdelaziz ◽  
...  

Doxorubicin is a drug that belongs to the anthracycline antibiotics. Nephrotoxicity is one of the serious side effects of doxorubicin treatment. Crocin, which is one of the most bioactive components of saffron, has antioxidant, anti-inflammatory, and antitumor effects. The current study was aimed at investigating the possible protective effects of crocin against doxorubicin-induced nephrotoxicity to elucidate the underlying mechanism of this effect. The study included four groups, six rats in each group: normal control, crocin control, doxorubicin, and crocin/doxorubicin. Doxorubicin and crocin/doxorubicin groups received intraperitoneal injections of doxorubicin (3.5 mg/kg twice weekly for 3 weeks). Rats in the crocin control group and the crocin/doxorubicin group were treated with intraperitoneal injections of crocin (100 mg/kg body weight per day) for 3 weeks. Biomarkers of kidney function and oxidative stress as well as the abundance of mRNA for nuclear factor-κβ and inducible nitric oxide synthase were evaluated. In addition, the abundance of cyclooxygenase 2 and tumor necrosis factor α immunoreactivity was evaluated. Crocin treatment had renoprotective effects manifested by significant improvement in kidney function as well as a reduction in the abundance of biomarkers of oxidative stress markers and inflammatory mediators. In conclusion, crocin has a protective effect against doxorubicin-induced nephrotoxicity in rats by serving as an antioxidant and attenuating the expression of NF-κB, iNOS, COX2, and TNFα.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Jacek Grebowski ◽  
Paulina Kazmierska ◽  
Anita Krokosz

Recently, much attention has been paid to the bioactive properties of water-soluble fullerene derivatives: fullerenols, with emphasis on their pro- and antioxidative properties. Due to their hydrophilic properties and the ability to scavenge free radicals, fullerenols may, in the future, provide a serious alternative to the currently used pharmacological methods in chemotherapy, treatment of neurodegenerative diseases, and radiobiology. Some of the most widely used drugs in chemotherapy are anthracycline antibiotics. Anthracycline therapy, in spite of its effective antitumor activity, induces systemic oxidative stress, which interferes with the effectiveness of the treatment and results in serious side effects. Fullerenols may counteract the harmful effects of anthracyclines by scavenging free radicals and thereby improve the effects of chemotherapy. Additionally, due to the hollow spherical shape, fullerenols may be used as drug carriers. Moreover, because of the existence of the currently ineffective ways for neurodegenerative diseases treatment, alternative compounds, which could prevent the negative effects of oxidative stress in the brain, are still sought. In the search of alternative methods of treatment and diagnosis, today’s science is increasingly reaching for tools in the field of nanomedicine, for example, fullerenes and their water-soluble derivatives, which is addressed in the present paper.


2021 ◽  
Vol 12 ◽  
Author(s):  
Fan Wan ◽  
Ruqing Zhong ◽  
Mengyu Wang ◽  
Yexun Zhou ◽  
Yuxia Chen ◽  
...  

Caffeic acid (CA) is one of the major phenolic acids of coffee with multiple biological activities. Our previous study found that 500 mg/kg of chlorogenic acid (CGA) had the potential capacity of alleviating colonic inflammation. Moreover, CGA can be degraded into caffeic acid (CA) by the gut microbiota in the colon. Therefore, we hypothesize that CA can exert protective effects on colonic inflammation. To test the hypothesis, 251 mg/kg CA was supplemented to DSS-induced colitis mice. The results showed that CA treatment recovered DSS-induced disease activity index (DAI), colon length, and histopathology scores of colon tissue. Additionally, CA treatment significantly decreased pro-inflammatory cytokines and malondialdehyde (MDA) levels and increased the level of IL-10, total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in serum. qPCR results indicated that CA treatment dramatically downregulated mRNA expression of IL-1β, IL-6, and TNF-α as well as upregulated SOD1, GPX1, GPX2, CAT, and IL-10. In addition, CA supplementation significantly increased mRNA expression of Nrf-2, HO-1, and NQO1, which showed its antioxidant and anti-inflammatory capacities potentially by activating the Nrf-2/HO-1 pathway. Moreover, CA supplementation prevented gut barrier damage by enhancing Occludin gene expression. Furthermore, CA supplementation altered the gut microbiome composition by decreasing the relative abundance of Bacteroides and Turicibacter, and enhancing the relative abundance of Alistipes and Dubosiella. Meanwhile, CA supplementation increases the abundance of Dubosiella and Akkermansia. In conclusion, CA supplementation could effectively alleviate DSS-induced colitis by improving the defense against oxidative stress and inflammatory response.


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