Z-505 hydrochloride ameliorates chemotherapy-induced anorexia in rodents via activation of the ghrelin receptor, GHSR1a

Shiomi, Yoshihiro; Ohira, Yuta; Yoshimura, Masashi; Ozaki, Tomoko; Takei, Makoto; Tanaka, Takao

doi:10.1016/j.ejphar.2017.10.047

Cited by 16 publications

(11 citation statements)

References 40 publications

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“…This finding confirms that cisplatin-induced toxicity was dose dependent. 7 Changes in body weight and food intake after each cisplatin injection were reported by Malik et al, 24 who showed that administration of cisplatin significantly reduces food intake on the first day following cisplatin, reaching a nadir at 2 days and progressively recovering thereafter. We also observed the same phenomenon, as shown in Figure 1A and B.…”

Section: Discussionmentioning

confidence: 82%

“…Anorexia is usually defined as loss of desire to eat. Numerous studies have shown that cisplatin adversely affects food intake, 3,5,7,23 which is significantly associated with declining body weight. In the present study, the toxic effects of cisplatin on appetite, body weight and feeding efficiency increased with accumulated treatment times and doses (Figure 2 E).…”

Section: Discussionmentioning

confidence: 99%

“…[3][4][5] Among chemotherapeutic agents, cisplatin is a first-line, standard care agent for lung cancer with strong emetic activity. There is evidence that cisplatin induces anorexia, loss of adipose tissue and skeletal muscle atrophy, 3,[5][6][7] indicating that cisplatin produces serious adverse effects that can lead patients to discontinuation of treatment. The incidence of anorexia is approximately 15% among patients with cancer receiving high-dose cisplatin treatment.…”

Section: Introductionmentioning

confidence: 99%

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D-Methionine Ameliorates Cisplatin-Induced Muscle Atrophy via Inhibition of Muscle Degradation Pathway

Liao

et al. 2019

Integr Cancer Ther

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Cisplatin induces anorexia, weight loss, loss of adipose tissue, skeletal muscle atrophy, and serious adverse effects that can cause premature termination of chemotherapy. The aim of this study was to use an animal model to assess cisplatin therapy (3 cycles) with and without d-methionine to investigate its protective effects on cisplatin-induced anorexia and skeletal muscle wasting. Wistar rats were divided into 3 groups and treated as follows: saline as control (group 1), intraperitoneal cisplatin once a week for 3 weeks (group 2), and intraperitoneal cisplatin once a week for 3 weeks plus oral administration of d-methionine (group 3). Tissue somatic index (TSI), gastric emptying index (GEI), and feeding efficiency were measured. Both hepatic lipid metabolism and muscle atrophy-related gene expressions and C2C12 myotubes were determined by polymerase chain reaction. Micro–computed tomography (micro-CT) was used to conduct assessment of bone microarchitecture indices. Pathological changes of the gastric mucosa were assessed by hematoxylin and eosin staining after euthanizing the animals. d-Methionine increased food intake, weight gain, gastric emptying, and feeding efficiency, as well as decrease stomach contents, after cisplatin injections. Cisplatin caused shortening of myofibers. Cisplatin-induced muscle mass wasting was mediated by the elevation of mRNA expressions of MAFbx and MuRF-1 in ubiquitin ligases in muscle tissue homogenate. The mRNA expressions of MyoD and myogenin, markers of muscle differentiation, declined following cisplatin administration. The administration of d-methionine not only led to significant improvements in myofiber diameter and cross-sectional fiber areas but also reversed muscle atrophy-related gene expression. However, there were no significant changes in stomach histology or microarchitecture of trabecular bone among the study groups. The results indicate that d-methionine has an appetite-enhancing effect and ameliorates cisplatin-induced adipose and muscle tissue loss during cisplatin-based chemotherapy.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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D-Methionine Ameliorates Cisplatin-Induced Muscle Atrophy via Inhibition of Muscle Degradation Pathway

Liao

et al. 2019

Integr Cancer Ther

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“…Recent studies confirmed that the level of ghrelin in the blood is decreased after chemotherapy such as oxaliplatin in animals as well as humans. Therefore, ghrelin may be related in chemotherapy-induced anorexia ( Shiomi et al, 2018 ).…”

Section: Gastrointestinal Toxicitymentioning

confidence: 99%

Multi-Component Herbal Products in the Prevention and Treatment of Chemotherapy-Associated Toxicity and Side Effects: A Review on Experimental and Clinical Evidences

et al. 2018

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Chemotherapy is nowadays the main treatment of human cancers. Chemotherapeutic agents target rapidly dividing cancer cells to suppress tumor progression, however, their non-specific cytotoxicity often leads to significant side effects that might be intolerable to cancer patients. Multi-component herbal products have been used for thousands of years for the treatment of multiple human diseases. This study aims to systematically summarize and evaluate the experimental and clinical evidences of the efficacy of multi-component herbal products in improving chemotherapy-induced side effect. Literature was retrieved from PubMed database and evaluated based on the side effects described. Multi-component herbal products were found to be effective in ameliorating the neurotoxicity, gastrointestinal toxicity, hematological toxicity, cardiotoxicity, hepatotoxicity and nephrotoxicity. Both experimental and clinical evidences were found, indicating the potential of applying multicomponent herbal products in the clinical treatment of chemotherapy-induced side effects. However, the lack of mechanistic and pharmacokinetic studies, inconsistency in product quality, as well as insufficient clinical evidence suggested that more investigations are urgently necessary. In all, our review shed light on the potential of using multi-component herbal products in the clinical management of chemotherapy-induced toxicity and side effects. We also discussed the potential threats of natural products for cancer treatment and compared the advantages of using herbs to conventional chemical drugs.

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“…Hexarelin and JMV2894 counteracted anorexia and preserved muscle function in rats with cisplatin-induced cachexia (Conte et al, 2017). Z-505 ameliorated chemotherapy-and cancer-induced cachexia-anorexia in rodents (Shiomi et al, 2018). Anamorelin was successfully used in clinical trials in cancer patients (Garcia et al, 2015;Temel et al, 2016;Currow et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

In Vitro and In Vivo Characterization of Novel Stable Peptidic Ghrelin Analogs: Beneficial Effects in the Settings of Lipopolysaccharide-Induced Anorexia in Mice

Holubová

Blechová

Kákonová

et al. 2018

J Pharmacol Exp Ther

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Ghrelin, the only known orexigenic gut hormone produced primarily in the stomach, has lately gained attention as a potential treatment of anorexia and cachexia. However, its biologic stability is highly limited; therefore, a number of both peptide and nonpeptide ghrelin analogs have been synthesized. In this study, we provide in vitro and in vivo characterization of a series of novel peptide growth hormone secretagogue receptor (GHS-R1a) agonists, both under nonpathologic conditions and in the context of lipopolysaccharide (LPS)-induced anorexia. These analogs were based on our previous series modified by replacing the Ser with diaminopropionic acid (Dpr), the N-terminal Gly with sarcosine, and Phe with various noncoded amino acids. New analogs were further modified by replacing the n-octanoyl bound to Dpr with longer or unsaturated fatty acid residues, by incorporation of the second fatty acid residue into the molecule, or by shortening the peptide chain. These modifications preserved the ability of ghrelin analogs to bind to the membranes of cells transfected with GHS-R1a, as well as the GHS-R1a signaling activation. The selected analogs exhibited long-lasting and potent orexigenic effects after a single s.c. administration in mice. The stability of new ghrelin analogs in mice after s.c. administration was significantly higher when compared with ghrelin and [Dpr]ghrelin, with half-lives of approximately 2 hours. A single s.c. injection of the selected ghrelin analogs in mice with LPS-induced anorexia significantly increased food intake via the activation of orexigenic pathways and normalized blood levels of proinflammatory cytokines, demonstrating the anti-inflammatory potential of the analogs.

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Z-505 hydrochloride ameliorates chemotherapy-induced anorexia in rodents via activation of the ghrelin receptor, GHSR1a

Cited by 16 publications

References 40 publications

D-Methionine Ameliorates Cisplatin-Induced Muscle Atrophy via Inhibition of Muscle Degradation Pathway

D-Methionine Ameliorates Cisplatin-Induced Muscle Atrophy via Inhibition of Muscle Degradation Pathway

Multi-Component Herbal Products in the Prevention and Treatment of Chemotherapy-Associated Toxicity and Side Effects: A Review on Experimental and Clinical Evidences

In Vitro and In Vivo Characterization of Novel Stable Peptidic Ghrelin Analogs: Beneficial Effects in the Settings of Lipopolysaccharide-Induced Anorexia in Mice

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