Molecular mechanism involved in cyclophosphamide-induced cardiotoxicity: Old drug with a new vision

Iqubal, Ashif; Iqubal, Mohammad Kashif; Sharma, Shrestha; Ansari, Mohd. Asif; Najmi, Abul Kalam; Ali, Syed Mansoor; Ali, Javed; Haque, Syed Ehtaishamul

doi:10.1016/j.lfs.2018.12.018

Cited by 211 publications

(181 citation statements)

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“…Although it has a wide spectrum of therapeutic applications, it is a cardiotoxic drug leading to endothelial impairment and destruction of myocardiocytes [29]. One of the main reasons for cyclophosphamide-induced cardiotoxicity is oxidative stress [9]. Oxidative stress may result in endothelial dysfunction, hypertrophy, fibrosis, inflammation, apoptosis, cell migration, and angiogenesis [30].…”

Section: Discussionmentioning

confidence: 99%

“…Mechanisms of cyclophosphamide-induced cardiotoxicity encompass oxidative and nitrative stress, protein adduct formation which leads to cardiomyocyte inflammation, altered calcium homeostasis, programmed cell death, swelling of the cardiomyocytes, nuclear splitting, vacuolization, and alteration in signaling pathways. ese events result in diseases of the heart muscle including heart failure, and if left untreated, this may result in death [9].…”

Section: Introductionmentioning

confidence: 99%

“…e inhibitory effect on xanthine oxidase activity might be another possible reason for the Croton macrostachyus protective effect. It was reported that cyclophosphamide increases myocardial xanthine oxidase activity and reduces the level of the antioxidant enzyme [9]. Xanthine oxidase is a flavoprotein, found in heart, kidney, lung, and vascular endothelium, which catalyzes the oxidation of hypoxanthine to xanthine and generates superoxide and uric acid and this leads to several diseases including CVDs [57].…”

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confidence: 99%

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Cardioprotective Effect of Croton macrostachyus Stem Bark Extract and Solvent Fractions on Cyclophosphamide‐Induced Cardiotoxicity in Rats

Ayza

Balasubramanian²,

Berhe

2020

Evidence-Based Complementary and Alternative Medicine

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Context. Croton macrostachyus Hochst. ex Delile (Euphorbiaceae) has been used in traditional medicine to manage heart failure and other heart diseases in Ethiopia. Objective. To evaluate the antioxidant and cardioprotective activities of stem bark extract and solvent fractions of Croton macrostachyus on cyclophosphamide-induced cardiotoxicity in rats. Materials and Methods. DPPH free radical scavenging assay method was used to determine antioxidant activity whereas Sprague-Dawley rats were used to evaluate the cardioprotective activity. Except for the normal control, all groups were subjected to cyclophosphamide (200 mg/kg, i.p.) toxicity on the first day. Enalapril at 10 mg/kg was used as a reference. The hydromethanolic crude extract (100, 200, and 400 mg/kg) and aqueous and ethyl acetate fractions (100 and 200 mg/kg, each) were administered for 10 days. The cardioprotective activities were evaluated using cardiac biomarkers such as Troponin I, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total cholesterol (TC), triglyceride (TG), and histopathological studies of heart tissue. Results. Crude extract and ethyl acetate and aqueous fractions exhibited free radical scavenging activities at IC50 of 594 μg/mL, 419 μg/mL, and 716 μg/mL, respectively. Crude extract at 400 mg/kg decreased the levels of troponin, AST, ALT, and ALP to 0.29 ± 0.06 ng/mL, 103.00 ± 7.63 U/L, 99.80 ± 6.18 U/L, and 108.80 ± 8.81 U/L, respectively. In addition, ethyl acetate fraction at 200 mg/kg decreased the levels of troponin, AST, ALT, and ALP to 0.22 ± 0.02 ng/mL, 137.00 ± 14.30 U/L, 90.33 ± 6.13 U/L, and 166.67 ± 13.50 U/L, respectively, compared with the cyclophosphamide control group. Conclusions. Croton macrostachyus possesses cardioprotective activities and it could be a possible source of treatment for cardiotoxicity induced by cyclophosphamide.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Cardioprotective Effect of Croton macrostachyus Stem Bark Extract and Solvent Fractions on Cyclophosphamide‐Induced Cardiotoxicity in Rats

Ayza

Balasubramanian²,

Berhe

2020

Evidence-Based Complementary and Alternative Medicine

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“…CP is a prodrug that gets metabolised into acrolein and phosphoramide mustard (PM) as a toxic and bioactive metabolite respectively. (Iqubal et al, ). Despite being a potential chemotherapeutic and immunosuppressant drug, the therapeutic use of CP remains constrained because of gonadal toxicities that it produces as side effects.…”

Section: Introductionmentioning

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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“…For instance, cyclophosphamide may actually cause harm through DNA damage, which induces more innate inflammation including through activation of the NLRP3 inflammasome. 31,32 • Ketogenic diet: a ketogenic diet has provided seizure efficacy in children with superrefractory status epilepticus, including some with FIRES. 33 Kramer et al reported that 7/63 children with FIRES in their large cohort received a ketogenic diet, with some of these children returning to baseline and others remaining in a vegetative state.…”

Section: Keep the Fire From Returningmentioning

confidence: 99%

Extinguishing Febrile Infection-Related Epilepsy Syndrome: Pipe Dream or Reality?

2020

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Febrile infection-related epilepsy syndrome (FIRES) is a rare and devastating epileptic encephalopathy with historically abysmal neurocognitive outcomes, including a high incidence of mortality. It tends to affect children and young adults and is characterized by superrefractory status epilepticus following a recent febrile illness. Growing evidence suggests a heterogeneous etiology resulting in fulminant nonantibody-mediated neuroinflammation. For some children with FIRES, this aberrant neuroinflammation appears secondary to a functional deficiency in the endogenous interleukin-1 receptor antagonist. A precise etiology has not been identified in all FIRES patients, and current treatments are not always successful. Limited treatment evidence exists to guide choice, dosing, and duration of therapies. However, the ketogenic diet and certain targeted immunomodulatory treatments, including anakinra, appear safe and have been associated with relatively excellent clinical outcomes in some FIRES patients. Future prospective multicenter collaborative studies are needed to further delineate the FIRES heterogeneous disease pathophysiology and to determine the safety and efficacy of treatment strategies through a robust measurement of neurocognitive outcomes.

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Molecular mechanism involved in cyclophosphamide-induced cardiotoxicity: Old drug with a new vision

Cited by 211 publications

References 214 publications

Cardioprotective Effect of Croton macrostachyus Stem Bark Extract and Solvent Fractions on Cyclophosphamide‐Induced Cardiotoxicity in Rats

Cardioprotective Effect of Croton macrostachyus Stem Bark Extract and Solvent Fractions on Cyclophosphamide‐Induced Cardiotoxicity in Rats

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

Extinguishing Febrile Infection-Related Epilepsy Syndrome: Pipe Dream or Reality?

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