Nerolidol attenuates cyclophosphamide-induced cardiac inflammation, apoptosis and fibrosis in Swiss Albino mice

The chemotherapeutic and immunosuppressive agent cyclophosphamide has previously been shown to induce complications within the setting of bone marrow transplantation. More recently, cardiotoxicity has been shown to be a dose-limiting factor during cyclophosphamide therapy, and cardiooncology is getting wider attention. Though mechanism of cyclophosphamide-induced cardiotoxicity is not completely understood, it is thought to encompass oxidative and nitrative stress. As such, this review focuses on antioxidants and their role in preventing or ameliorating cyclophosphamide-induced cardiotoxicity. It will give special emphasis to the cardioprotective effects of natural, plant-derived antioxidants that have garnered significant interest in recent times.

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“…Iqubal et al [73] Male Swiss albino mice Animals were treated with nerolidol (NER) (200 and 400 mg/kg p.o.) and fenofibrate (FF) 80 mg/kg, p.o.…”

Section: Oxidative Medicine and Cellular Longevitymentioning

confidence: 99%

The Role of Antioxidants in Ameliorating Cyclophosphamide-Induced Cardiotoxicity

Ayza

Zewdie

Tesfaye

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Nerolidol has already been reported with antioxidant, anti-inflammatory, anticonvulsant and antimicrobial properties (Chan, Tan, Chan, Lee, & Goh, 2016). Recently, we have reported the protective effect of NER against cyclophosphamide-induced cardioprotective and neuroprotective manifestations (Ansari, Iqubal, Ekbbal, & Haque, 2019;Iqubal, Sharma, Ansari, et al, 2019). Thus, NER owning antioxidant and anti-inflammatory property can prove to be effective in counteracting gonadal toxicities induced by CP.…”

mentioning

confidence: 99%

Ameliorative effect of nerolidol on cyclophosphamide‐induced gonadal toxicity in Swiss Albino mice: Biochemical‐, histological‐ and immunohistochemical‐based evidences

et al. 2020

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Cyclophosphamide (CP) is commonly used as antineoplastic and immunosuppressant drug with noticeable gonadotoxic profile. Nerolidol (NER) is a sesquiterpene with potent antioxidant and anti‐inflammatory properties. Thus, the present study was designed to explore its possible gonadal protective potential against cyclophosphamide‐induced testicular, epididymal, seminal and spermatozoal toxicities. Animals were divided into five groups: control (normal saline for 14 days), treatment group (NER 200 and 400 mg/kg, p.o) for 14 days along with a single dose of cyclophosphamide (200 mg/kg, i.p) on 7th day, toxic and Per se groups (cyclophosphamide 200 mg/kg i.p) on 7th day and NER 400 mg/kg for 14 days respectively. Animals were sacrificed on the 15 day, and body weight, weight of reproductive organs, testosterone level, sperm count, biochemical parameters, histopathological and immunohistochemical studies were performed in the testes, epididymis and in the serum. CP administration induced oxidative stress, nitrative stress, inflammation, reduced testosterone level, sperm count, increased expression of MPO and caused histological aberrations in the testes, epididymis and seminal vesicles. CP caused reduced sperm count, sperm motility and testosterone level which got reversed upon treatment with nerolidol in a dose‐dependent manner. Nerolidol thus acted as a gonadoprotective molecule and prevented the gonadotoxicity of CP.

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“…Although several studies have reported pro brotic effects of anthracyclines, cyclophosphamide, paclitaxel and trastuzumab in the myocardium of experimental models of cardiotoxicity [8][9][10][11][12][13][14], and in rodent cardiac broblasts [9,11], the role of these agents in HCFs has not been characterized. In this regard, we describe that doxorubicin, cyclophosphamide and trastuzumab stimulated the differentiation to a myo broblast collagen-synthesizing phenotype, including enhanced presence of PICP in the extracellular medium.…”

Section: Discussionmentioning

confidence: 99%

“…Traditionally, cardiotoxicity due to breast cancer treatment, particularly anthracycline-based cancer chemotherapy (ACC), has been attributed to cardiomyocyte damage and death, with amino-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponins (hs-Tn) as the most commonly used biomarkers to detect cardiac damage in these patients [5,6]. However, it has been suggested that myocardial interstitial brosis (MIF) is an additional important mechanism contributing to left ventricular dysfunction (LVD) and adverse clinical evolution in ACC-treated patients [6,7], as well as in patients treated with other oncologic drugs such as cyclophosphamide, taxane agents and anti-HER2 therapies [8][9][10][11][12][13][14]. As cumulative evidence suggest that the detrimental impact of MIF on LV function is related to both an excess in collagen type-I ber cross-linking and deposition [15], these characteristics of the collagen ber should be evaluated in the myocardium of patients receiving ACC.…”

Section: Introductionmentioning

confidence: 99%

Increased Serum Procollagen Type I C-terminal Propeptide Levels are Associated with Subclinical Left Ventricular Dysfunction in Patients with Breast Cancer Treated with Anthracycline-Based Cancer Chemotherapy

Adl

Santisteban

Lupón

et al. 2020

Preprint

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Background Anthracycline-based cancer chemotherapy (ACC) has been related to myocardial interstitial fibrosis (MIF), a lesion contributing to left ventricular dysfunction (LVD). We investigated whether biomarker-assessed MIF was associated with LVD in patients with breast cancer receiving ACC and in patients with ACC-induced heart failure (ACC-HF). Moreover, chemotherapy agent’s pro-fibrotic activity was evaluated in human cardiac fibroblasts (HCFs). Methods Echocardiography, serum biomarkers of collagen deposition (procollagen type-I C-terminal-propeptide [PICP]) and crosslinking (collagen type-I C-terminal-telopeptide/matrix metalloproteinase-1 ratio), and biomarkers of myocardial and vascular stress (galectin-3, sST2, amino-terminal pro-brain natriuretic peptide [NT-proBNP], hs-troponin-T and vascular cell adhesion molecule-1 [VCAM-1]) were assessed in 70 breast cancer patients at baseline, and during ACC at 3 and 6 months. Subclinical cardiotoxicity was defined as global longitudinal strain (GLS) relative reduction>15%. In addition, PICP and NT-proBNP were determined in 347 patients with different HF etiologies, 37 with ACC-HF (of whom 65% had been diagnosed with breast cancer) and 12-month-follow-up LVEF assessment. HCFs activation was examined after incubation with doxorubicin, cyclophosphamide, paclitaxel and trastuzumab for 24 hours. Results In patients with breast cancer, six-months-ACC reduced GLS and upregulated PICP, hs-troponin-T, NT-proBNP and VCAM-1 (P<0.01) versus baseline. At 6 months, elevation of PICP was higher in patients with subclinical cardiotoxicity versus the remaining patients (P for interaction<0.001). PICP levels were directly and independently associated with a relative reduction in GLS (P<0.001). In ACC-HF patients, baseline LVEF was inversely associated with PICP and NT-proBNP (P<0.01). After 12 months, LVEF did not change in patients with higher basal PICP (3rd tertile) but improved in the remaining patients (P<0.001). Doxorubicin, cyclophosphamide and trastuzumab stimulated collagen synthesis in HCFs. Conclusion These results indicate that biomarker-assessed MIF associates with early LVD in ACC-treated patients with breast cancer. In addition, these findings suggest that MIF may be associated with established LVD in ACC-HF patients, hindering LV functional improvement after 12 months. Finally, chemotherapy can directly activate collagen metabolism in HCFs.

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Nerolidol attenuates cyclophosphamide-induced cardiac inflammation, apoptosis and fibrosis in Swiss Albino mice

Cited by 56 publications

References 50 publications

The Role of Antioxidants in Ameliorating Cyclophosphamide-Induced Cardiotoxicity

The Role of Antioxidants in Ameliorating Cyclophosphamide-Induced Cardiotoxicity

Ameliorative effect of nerolidol on cyclophosphamide‐induced gonadal toxicity in Swiss Albino mice: Biochemical‐, histological‐ and immunohistochemical‐based evidences

Increased Serum Procollagen Type I C-terminal Propeptide Levels are Associated with Subclinical Left Ventricular Dysfunction in Patients with Breast Cancer Treated with Anthracycline-Based Cancer Chemotherapy

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