Cardioprotective Effects of Oroxylum indicum Extract Against Doxorubicin and Cyclophosphamide-Induced Cardiotoxicity

Pondugula, Satyanarayana R.; Harshan, Aisha; Ramesh, Sindhu; Govindarajulu, Manoj; Almaghrabi, Mohammed; Majrashi, Mohammed; Abbott, Kodye L.; Nadar, Rishi M.; Alturki, Mansour; Salamat, Julia M.; Smith, Forrest; Majeed, Muhammed; Nagabhushanam, Kalyanam; Moore, Timothy; Ren, Jun; Dhanasekaran, Muralikrishnan

doi:10.1007/s12012-021-09701-x

Cited by 11 publications

(9 citation statements)

References 41 publications

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“…Complex‐I (NADH dehydrogenase) in the mitochondria catalyzes the conversion of NADH oxidation to NAD+. A standard curve was obtained using NADH 23,25–27 …”

Section: Methodsmentioning

confidence: 99%

“…ROS content was determined by detecting the conversion of nonfluorescent chloromethyl‐DCF‐DA (2′, 7‐dichlorofluorescindiacetate, DCF‐DA) to fluorescent DCF using an excitation wavelength of 492 nm and an emission wavelength of 527 nm. This was done using spectrofluorometry 23,25–28 …”

Section: Methodsmentioning

confidence: 99%

“…A standard curve was obtained using hydrogen peroxide. 25,29 2.14 | Activity of superoxide dismutase SOD activity was measured using pyrogallol as the substrate. The activity of superoxide dismutase was measured at 420 nm and reported as a percentage change from the control.…”

Section: Activity Of Catalasementioning

confidence: 99%

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Evaluate the in vitro effect of anthracycline and alkylating cytophosphane chemotherapeutics on dopaminergic neurons

Desai,

Majrashi,

Pathak

et al. 2024

Cancer Reports

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BackgroundIatrogenesis is an inevitable global threat to healthcare that drastically increases morbidity and mortality. Cancer is a fatal pathological condition that affects people of different ages, sexes, and races around the world. In addition to the detrimental cancer pathology, one of the most common contraindications and challenges observed in cancer patients is severe adverse drug effects and hypersensitivity reactions induced by chemotherapy. Chemotherapy‐induced cognitive neurotoxicity is clinically referred to as Chemotherapy‐induced cognitive impairment (CICI), chemobrain, or chemofog. In addition to CICI, chemotherapy also causes neuropsychiatric issues, mental disorders, hyperarousal states, and movement disorders. A synergistic chemotherapy regimen of Doxorubicin (Anthracycline‐DOX) and Cyclophosphamide (Alkylating Cytophosphane‐CPS) is indicated for the management of various cancers (breast cancer, lymphoma, and leukemia). Nevertheless, there are limited research studies on Doxorubicin and Cyclophosphamide's pharmacodynamic and toxicological effects on dopaminergic neuronal function.AimThis study evaluated the dopaminergic neurotoxic effects of Doxorubicin and Cyclophosphamide.Methods and ResultsDoxorubicin and Cyclophosphamide were incubated with dopaminergic (N27) neurons. Neuronal viability was assessed using an MTT assay. The effect of Doxorubicin and Cyclophosphamide on various prooxidants, antioxidants, mitochondrial Complex‐I & IV activities, and BAX expression were evaluated by Spectroscopic, Fluorometric, and RT‐PCR methods, respectively. Prism‐V software (La Jolla, CA, USA) was used for statistical analysis. Chemotherapeutics dose‐dependently inhibited the proliferation of the dopaminergic neurons. The dopaminergic neurotoxic mechanism of Doxorubicin and Cyclophosphamide was attributed to a significant increase in prooxidants, a decrease in antioxidants, and augmented apoptosis without affecting mitochondrial function.ConclusionThis is one of the first reports that reveal Doxorubicin and Cyclophosphamide induce significant dopaminergic neurotoxicity. Thus, Chemotherapy‐induced adverse drug reaction issues substantially persist during and after treatment and sometimes never be completely resolved clinically. Consequently, failure to adopt adequate patient care measures for cancer patients treated with certain chemotherapeutics might substantially raise the incidence of numerous movement disorders.

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“…Complex‐I (NADH dehydrogenase) in the mitochondria catalyzes the conversion of NADH oxidation to NAD+. A standard curve was obtained using NADH 23,25–27 …”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Evaluate the in vitro effect of anthracycline and alkylating cytophosphane chemotherapeutics on dopaminergic neurons

Desai,

Majrashi,

Pathak

et al. 2024

Cancer Reports

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“…Oroxylum indicum extract (OIE) significantly reduces caspase-3 and protease activity in the hearts of DOX- and CP-treated C57BL/6 J mice ( 127 ). Maltol (produced by heating Panax ginseng ) enhanced PI3K/Akt expression levels and reduced CP-induced apoptosis in H9C2 cardiomyocytes during cisplatin treatment ( 128 ) ( Figure 4 ).…”

Section: Molecular Mechanisms Of Chemoradiotherapy-related Cardiotoxi...mentioning

confidence: 99%

Role and molecular mechanism of traditional Chinese medicine in preventing cardiotoxicity associated with chemoradiotherapy

Wen

et al. 2022

Front. Cardiovasc. Med.

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Cardiotoxicity is a serious complication of cancer therapy. It is the second leading cause of morbidity and mortality in cancer survivors and is associated with a variety of factors, including oxidative stress, inflammation, apoptosis, autophagy, endoplasmic reticulum stress, and abnormal myocardial energy metabolism. A number of studies have shown that traditional Chinese medicine (TCM) can mitigate chemoradiotherapy-associated cardiotoxicity via these pathways. Therefore, this study reviews the effects and molecular mechanisms of TCM on chemoradiotherapy-related cardiotoxicity. In this study, we searched PubMed for basic studies on the anti-cardiotoxicity of TCM in the past 5 years and summarized their results. Angelica Sinensis, Astragalus membranaceus Bunge, Danshinone IIA sulfonate sodium (STS), Astragaloside (AS), Resveratrol, Ginsenoside, Quercetin, Danggui Buxue Decoction (DBD), Shengxian decoction (SXT), Compound Danshen Dripping Pill (CDDP), Qishen Huanwu Capsule (QSHWC), Angelica Sinensis and Astragalus membranaceus Bunge Ultrafiltration Extract (AS-AM),Shenmai injection (SMI), Xinmailong (XML), and nearly 60 other herbs, herbal monomers, herbal soups and herbal compound preparations were found to be effective as complementary or alternative treatments. These preparations reduced chemoradiotherapy-induced cardiotoxicity through various pathways such as anti-oxidative stress, anti-inflammation, alleviating endoplasmic reticulum stress, regulation of apoptosis and autophagy, and improvement of myocardial energy metabolism. However, few clinical trials have been conducted on these therapies, and these trials can provide stronger evidence-based support for TCM.

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“…Therefore, overcoming this adverse effect is so vital for accomplishing a favorable outcome in cancer patients. 1,2 Cardiotoxicity of CP is usually observed after administration of high doses. Although the associated clinical manifestations and cardiotoxic hazards are well-documented, the underlying mechanisms are still not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Role of hypoxia inducible factor/vascular endothelial growth factor/endothelial nitric oxide synthase signaling pathway in mediating the cardioprotective effect of dapagliflozin in cyclophosphamide-induced cardiotoxicity

et al. 2023

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Background Cyclophosphamide (CP) is a commonly used chemotherapeutic and immunosuppressive alkylating agent. However, cardiac adverse effects of CP interfere with its clinical benefit. Cardio-oncology research is currently an important issue and finding effective cardiopreserving agents is a critical need. For the first time, we aimed to detect if dapagliflozin (DAP) could ameliorate CP-induced cardiac injury and investigated the role of hypoxia inducible factor α (HIF1α)/vascular endothelial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS) pathway. Methods Forty male Wistar albino rats were included in the current model. Studied groups are: control group; CP-induced cardiotoxicity group; CP group treated with DAP; CP group treated with DAP and administered a nitric oxide synthase inhibitor; nitro-ω-L-arginine (L-NNA) before DAP to explore the role of eNOS. Results Our data revealed that CP could induce cardiac damage as manifested by significant increases in cardiac enzymes, blood pressure, malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), HIF1α, sodium glucose co-transporter 2 (SGLT2) and cleaved caspase-3 levels with toxic histopathological changes. However, there are significant decreases in reduced glutathione (GSH), total antioxidant capacity (TAC), VEGF, and eNOS. On the opposite side, co-administration of DAP showed marked improvement of CP-induced cardiac damage that may be due to its ability to inhibit SGLT2, antioxidant, anti-inflammatory and anti-apoptotic properties. Results showed decreasing the cardioprotective effect of DAP on administration of L-NNA, reflecting the critical effect of eNOS in mediating such protection. Conclusion DAP could reduce CP cardiotoxicity based upon its ability to modulate SGLT2 and HIF1α/VEGF/eNOS signaling pathway.

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Cardioprotective Effects of Oroxylum indicum Extract Against Doxorubicin and Cyclophosphamide-Induced Cardiotoxicity

Cited by 11 publications

References 41 publications

Evaluate the in vitro effect of anthracycline and alkylating cytophosphane chemotherapeutics on dopaminergic neurons

Evaluate the in vitro effect of anthracycline and alkylating cytophosphane chemotherapeutics on dopaminergic neurons

Role and molecular mechanism of traditional Chinese medicine in preventing cardiotoxicity associated with chemoradiotherapy

Role of hypoxia inducible factor/vascular endothelial growth factor/endothelial nitric oxide synthase signaling pathway in mediating the cardioprotective effect of dapagliflozin in cyclophosphamide-induced cardiotoxicity

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