A review of the logistic role of <scp>l</scp>‐carnitine in the management of radiation toxicity and radiotherapy side effects

Khan, Haseeb A.; Alhomida, Abdullah S.

doi:10.1002/jat.1716

Cited by 41 publications

(28 citation statements)

References 94 publications

(105 reference statements)

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“…Despite the recent advancements in chemotherapeutics, chemotherapy is still associated with severe adverse effects such as nephrotoxicity, nausea, hair loss, skin irritation, anemia, and infertility [38], [39]. Therefore, naturally occurring anticancer compounds from natural plants, especially those with low toxicity and high potency, have important implications for chemotherapy and chemoprevention.…”

Section: Discussionmentioning

confidence: 99%

Soluble Extract from Moringa oleifera Leaves with a New Anticancer Activity

2014

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Moringa oleifera has been regarded as a food substance since ancient times and has also been used as a treatment for many diseases. Recently, various therapeutic effects of M. oleifera such as antimicrobial, anticancer, anti-inflammatory, antidiabetic, and antioxidant effects have been investigated; however, most of these studies described only simple biological phenomena and their chemical compositions. Due to the increasing attention on natural products, such as those from plants, and the advantages of oral administration of anticancer drugs, soluble extracts from M. oleifera leaves (MOL) have been prepared and their potential as new anticancer drug candidates has been assessed in this study. Here, the soluble cold Distilled Water extract (4°C; concentration, 300 µg/mL) from MOL greatly induced apoptosis, inhibited tumor cell growth, and lowered the level of internal reactive oxygen species (ROS) in human lung cancer cells as well as other several types of cancer cells, suggesting that the treatment of cancer cells with MOL significantly reduced cancer cell proliferation and invasion. Moreover, over 90% of the genes tested were unexpectedly downregulated more than 2-fold, while just below 1% of the genes were upregulated more than 2-fold in MOL extract-treated cells, when compared with nontreated cells. Since severe dose-dependent rRNA degradation was observed, the abnormal downregulation of numerous genes was considered to be attributable to abnormal RNA formation caused by treatment with MOL extracts. Additionally, the MOL extract showed greater cytotoxicity for tumor cells than for normal cells, strongly suggesting that it could potentially be an ideal anticancer therapeutic candidate specific to cancer cells. These results suggest the potential therapeutic implications of the soluble extract from MOL in the treatment of various types of cancers.

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Section: Discussionmentioning

confidence: 99%

Soluble Extract from Moringa oleifera Leaves with a New Anticancer Activity

2014

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“…TML is further oxidized to γ-butyrobetaine, which is hydroxylated in the liver and kidney to form carnitine (33). Inside the mitochondria, the carnitine conjugate acetylcarnitine regulates the levels of acetyl-CoA (35), which is essential for the balance between fatty acid and carbohydrate metabolism (30). Acetylcarnitine, found to be retained intracellularly by monitoring the urinary levels (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

Development of a Metabolomic Radiation Signature in Urine from Patients Undergoing Total Body Irradiation

et al. 2014

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The emergence of the threat of radiological terrorism and other radiological incidents has led to the need for development of fast, accurate and noninvasive methods for detection of radiation exposure. The purpose of this study was to extend radiation metabolomic biomarker discovery to humans, as previous studies have focused on mice. Urine was collected from patients undergoing total body irradiation at Memorial Sloan-Kettering Cancer Center prior to hematopoietic stem cell transplantation at 4–6 h postirradiation (a single dose of 1.25 Gy) and 24 h (three fractions of 1.25 Gy each). Global metabolomic profiling was obtained through analysis with ultra performance liquid chromatography coupled to time-of-flight mass spectrometry (TOFMS). Prior to further analyses, each sample was normalized to its respective creatinine level. Statistical analysis was conducted by the nonparametric Kolmogorov-Smirnov test and the Fisher’s exact test and markers were validated against pure standards. Seven markers showed distinct differences between pre- and post-exposure samples. Of those, trimethyl-l-lysine and the carnitine conjugates acetylcarnitine, decanoylcarnitine and octanoylcarnitine play an important role in the transportation of fatty acids across mitochondria for subsequent fatty acid β-oxidation. The remaining metabolites, hypoxanthine, xanthine and uric acid are the final products of the purine catabolism pathway, and high levels of excretion have been associated with increased oxidative stress and radiation induced DNA damage. Further analysis revealed sex differences in the patterns of excretion of the markers, demonstrating that generation of a sex-specific metabolomic signature will be informative and can provide a quick and reliable assessment of individuals in a radiological scenario. This is the first radiation metabolomics study in human urine laying the foundation for the use of metabolomics in biodosimetry and providing confidence in biomarker identification based on the overlap between animal models and humans.

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“…The pathological process of radiation injury begins immediately after radiation exposure, but the clinical features may not present for weeks, months, or even years after treatment completion [2,6]. Fatigue induced by RT may be the body’s response to a toxic insult [38].…”

Section: Proposed Mechanisms Of Rifmentioning

confidence: 99%

“…Localized or total body RT is used as a primary, neo-adjuvant or adjuvant combination modality with surgery, chemotherapy, hormone therapy, or immunotherapy across different stages of cancer [2]. While external beam intensity modulated RT successfully increases disease-free survival rates and life expectancy, ionizing radiation leads to increased treatment-related adverse effects.…”

Section: Introductionmentioning

confidence: 99%

The Etiology and management of radiotherapy-induced fatigue

Hsiao

Daly

Saligan

2016

Expert Review of Quality of Life in Cancer Care

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Fatigue is one of the most common side-effects accompanying radiotherapy, but arguably the least understood. Radiotherapy-induced fatigue (RIF) is a clinical subtype of cancer treatment-related fatigue. It is described as a pervasive, subjective sense of tiredness persisting over time, interferes with activities of daily living, and is not relieved by adequate rest or sleep. RIF is one of the early side-effects and long-lasting for cancer patients treated with localized radiation. Although the underlying mechanisms of fatigue have been studied in several disease conditions, the etiology, mechanisms, and risk factors of RIF remain elusive, and this symptom remains poorly managed. The purpose of this paper is to review and discuss recent articles that defined, proposed biologic underpinnings and mechanisms to explain the pathobiology of RIF, as well as articles that proposed interventions to manage RIF. Understanding the mechanisms of RIF can describe promising pathways to identify at-risk individuals and identify potential therapeutic targets to alleviate and prevent RIF using a multimodal, multidisciplinary approach.

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A review of the logistic role of l‐carnitine in the management of radiation toxicity and radiotherapy side effects

Cited by 41 publications

References 94 publications

Soluble Extract from Moringa oleifera Leaves with a New Anticancer Activity

Soluble Extract from Moringa oleifera Leaves with a New Anticancer Activity

Development of a Metabolomic Radiation Signature in Urine from Patients Undergoing Total Body Irradiation

The Etiology and management of radiotherapy-induced fatigue

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