Myelotoxicity of carboplatin is increased in vivo in db/db mice, the animal model of obesity-associated diabetes mellitus

Géresi, Krisztina; Megyeri, A; Szabo, Barbara; Szabó, Zsolt; Aradi, J.; Németh, József; Benkö, Ilona

doi:10.1007/s00280-015-2679-x

Cited by 6 publications

(5 citation statements)

References 42 publications

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“…The results showed an increase in suppression of bone marrow and induction of neutropenia by carboplatin with higher myelotoxicity in db/db mice for each of the cytotoxic drugs. Furthermore, a two‐ to five‐fold increase in myelotoxicity for each cytotoxic drug was seen on CFU‐GM, indicating a defect in hematopoietic progenitor cells in obesity‐associated diabetes (Géresi et al, ).…”

Section: Resultsmentioning

confidence: 99%

The effect of diabetes mellitus on pharmacokinetics, pharmacodynamics and adverse drug reactions of anticancer drugs

Mashayekhi‐Sardoo

Mohammadpour

Nomani

et al. 2019

Journal Cellular Physiology

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Diabetes mellitus (DM) and cancer are global problems carrying huge human, social, and economic impact. Type 2 diabetes (T2DM) is associated with an increased risk for a number of cancers, including breast, pancreatic, and liver cancer. Moreover, adverse drug reactions are higher in paitents with cancer with T2DM compared to cancer patients without T2DM. Cellular mechanisms of hyperglycemia and chemotherapy efficacy may be different depending upon the particular cancer type and the condition of the patient. This review evaluates the effect of DM on the pharmacokinetic, pharmacodynamic, and adverse drug reactions of commonly used anticancer drugs such as cisplatin, methotrexate, paclitaxel, doxorubicin, and adriamycin in both clinical and animal models. A literature search was conducted in scientific databases including Web of Science, PubMed, Scopus, and Google Scholar including the relevant keywords. The results of the effectiveness of anticancer therapies in patients with DM are, however, inconsistent because DM can negativelyimpact multiple diverse entities including nerves and vascular structures, insulin-like growth factor 1, the function of the innate immune system, drug pharmacokinetics, the expression levels of hepatic CYP 450 , Mdr 1b and enzymes that then lead to drug toxicity. However, in a few circumstances, DM led to attenuation of the toxicity of anticancer drugs secondary to attenuation of the energy-dependent renal uptake process. Overall, the impact of DM on patients with cancer is variable because of the diverse types of cancers and the spectrum of anticancer drugs. With respect to the evidence for cancer involvement in DM pathophysiology and the response to anticancer treatment in patients with DM, many questions still remain and further clinical trials are needed.

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Section: Resultsmentioning

confidence: 99%

The effect of diabetes mellitus on pharmacokinetics, pharmacodynamics and adverse drug reactions of anticancer drugs

Mashayekhi‐Sardoo

Mohammadpour

Nomani

et al. 2019

Journal Cellular Physiology

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“…These observations suggested that obese Zucker rats may be more susceptible to 3-MCPD-dependent toxicity in the hematopoietic tissue than their lean counterparts. Previous studies have also demonstrated that anticancer agent-induced myelotoxicity is more severe in rodent models of obesity including obese Zucker rats and db/db mice, than in controls (Géresi et al, 2012(Géresi et al, , 2015. In addition, recent epidemiological studies have shown that obesity is significantly associated with iron deficiency, leading to anemia (Becker et al, 2015;Zhao et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Altered susceptibility of an obese rat model to 13-week subchronic toxicity induced by 3-monochloropropane-1,2-diol

et al. 2017

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-3-Monochloropropane-1,2-diol (3-MCPD) is a heat-induced food contaminant that has been shown to be a nongenotoxic renal carcinogen. Although the toxicity of 3-MCPD has been widely investigated for decades, there is a further concern that 3-MCPD might exert more potent toxicity in highrisk population with underlying diseases such as hyperlipidemia associated with obesity. In the present study, we performed a 13-week subchronic toxicity study for 3-MCPD using an obesity rat model to investigate the differences in susceptibility between obese and normal individuals. Male F344 and obese Zucker (lean and fatty) rats were administered 0, 9, 28.5, 90, 285, or 900 ppm 3-MCPD in drinking water for 13 weeks. 3-MCPD treatment decreased body weight gain, increased relative kidney weights, induced anemia, and induced epithelial cell necrosis in epididymal ducts in all 3 strains. The degrees of epididymal damage were higher in F344 and lean rats than in fatty rats, while renal toxicity was most potent in F344 rats and comparable in lean and fatty rats. In contrast, the hematology data indicated that anemia was worse in fatty rats than in F344 and lean rats, and a significant decrease in hematopoietic cells in the bone marrow was observed only in fatty rats. The no-observed-adverse-effect level was estimated to be 28.5 ppm in all 3 strains for 3-MCPD. These results suggested that obese Zucker rats may be more susceptible to 3-MCPD-dependent toxicity in the hematopoietic tissues than their lean counterparts.

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“…Another study showed that increasing DNA fragmentation in BM cells from rat models receiving carboplatin treatment was linked to rising HPCs apoptosis [ 62 ]. Apoptosis of HPCs and myelosuppression are also linked to increased DNA fragmentation, according to two further investigations using carboplatin [ 63 , 64 ]. Therefore, the acute BM injury is mainly due to the apoptosis induced by chemotherapy in the rapidly proliferating HPCs [ 65 ].…”

Section: Mechanismmentioning

confidence: 99%

Chemotherapy-induced thrombocytopenia: literature review

2023

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Chemotherapy-induced thrombocytopenia (CIT) is a common condition that frequently results in reduced chemotherapy dosages, postponed treatment, bleeding, and unfavorable oncological outcomes. At present, there is no clear suggestions for preventing or treating CIT. Thrombopoietin (TPO) replacement therapy has been invented and used to treat CIT to promote the production of megakaryocytes and stimulate the formation of platelets. However, this treatment is limited to the risk of immunogenicity and cancer progression. Therefore, an unmet need exists for exploring alternatives to TPO to address the clinical issue of CIT. Application of appropriate therapeutic drugs may be due to understanding the potential mechanisms of CIT. Studies have shown that chemotherapy significantly affects various cells in bone marrow (BM) microenvironment, reduces their ability to support normal hematopoiesis, and may lead to BM damage, including CIT in cancer patients. This review focuses on the epidemiology and treatment of cancer patients with CIT. We also introduce some recent progress to understand the cellular and molecular mechanisms of chemotherapy inhibiting normal hematopoiesis and causing thrombocytopenia.

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Myelotoxicity of carboplatin is increased in vivo in db/db mice, the animal model of obesity-associated diabetes mellitus

Cited by 6 publications

References 42 publications

The effect of diabetes mellitus on pharmacokinetics, pharmacodynamics and adverse drug reactions of anticancer drugs

The effect of diabetes mellitus on pharmacokinetics, pharmacodynamics and adverse drug reactions of anticancer drugs

Altered susceptibility of an obese rat model to 13-week subchronic toxicity induced by 3-monochloropropane-1,2-diol

Chemotherapy-induced thrombocytopenia: literature review

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