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chemotherapy induced hepatotoxicity

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https://www.readbyqxmd.com/read/29897226/alleviating-the-liver-toxicity-of-chemotherapy-via-ph-responsive-hepatoprotective-prodrug-micelles
#1
Ran Tao, Min Gao, Fang Liu, Xuliang Guo, Aiping Fan, Dan Ding, Deling Kong, Zheng Wang, Yanjun Zhao
Nanocarriers have been extensively utilized to enhance the anti-tumor performance of chemotherapy, but it is very challenging to eliminate the associated hepatotoxicity. This was due to the significant liver accumulation of cytotoxic drug-loaded nanocarriers as a consequence of systemic biodistribution. To address this, we report a novel type of nanocarrier that was made of hepatoprotective compound (oleanolic acid/OA) with a model drug (methotrexate/MTX) being physically encapsulated. OA was covalently connected with methoxy poly(ethylene glycol) (mPEG) via a hydrazone linker, generating amphiphilic mPEG-OA prodrug conjugate that could self-assemble into pH-responsive micelles (ca...
June 13, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29892148/protective-effects-of-eugenol-against-hepatotoxicity-induced-by-arsenic-trioxide-an-antileukemic-drug
#2
Prakash Binu, Nellikunnath Priya, Surendran Abhilash, Radhakrishnan Chandraprabha Vineetha, Harikumaran Nair
Background: Arsenic trioxide (As2O3) has shown effectiveness in the treatment of leukemia, but it is also associated with hepatotoxicity. Given antileukemic drug-induced oxidative stress and toxicity, this study focused on the mitigatory role of eugenol, a monoterpene compound from clove oil, in the hepatic tissue of Wistar rats. Methods: Twenty-four male Wistar rats (180-250 g) were randomly divided into 4 groups (6 rats per group): normal control rats, rats treated with As2 O2 (4 mg/kg bwt), rats treated with eugenol (5 mg/kg bwt), and rats receiving co-treatment with As2 O3 (4 mg/kg bwt) and eugenol (5 mg/kg bwt), all of which orally administered for a period of 30 days...
May 2018: Iranian Journal of Medical Sciences
https://www.readbyqxmd.com/read/29879147/interrogation-of-transcriptomic-changes-associated-with-drug-induced-hepatic-sinusoidal-dilatation-in-colorectal-cancer
#3
Monika A Jarzabek, William R Proctor, Jennifer Vogt, Rupal Desai, Patrick Dicker, Gary Cain, Rajiv Raja, Jens Brodbeck, Dale Stevens, Eric P van der Stok, John W M Martens, Cornelis Verhoef, Priti S Hegde, Annette T Byrne, Jacqueline M Tarrant
Drug-related sinusoidal dilatation (SD) is a common form of hepatotoxicity associated with oxaliplatin-based chemotherapy used prior to resection of colorectal liver metastases (CRLM). Recently, hepatic SD has also been associated with anti-delta like 4 (DLL4) cancer therapies targeting the NOTCH pathway. To investigate the hypothesis that NOTCH signaling plays an important role in drug-induced SD, gene expression changes were examined in livers from anti-DLL4 and oxaliplatin-induced SD in non-human primate (NHP) and patients, respectively...
2018: PloS One
https://www.readbyqxmd.com/read/29774103/bevacizumab-exacerbates-sinusoidal-obstruction-syndrome-sos-in-the-animal-model-and-increases-mmp-9-production
#4
Azin Jafari, Hanno Matthaei, Sven Wehner, Tolga Tonguc, Jörg C Kalff, Steffen Manekeller
Background: Thanks to modern multimodal treatment the ouctome of patients with colorectal cancer has experienced significant improvements. As a downside, agent specific side effects have been observed such as sinusoidal obstruction syndrome (SOS) after oxaliplatin chemotherapy (OX). Bevazicumab targeting VEGF is nowadays comprehensively used in combination protocols with OX but its impact on hepatotoxicity is thus far elusive and focus of the present study. Results: After MCT administration 67% of animals developed SOS...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29761566/nanomaterial-based-organelles-protect-normal-cells-against-chemotherapy-induced-cytotoxicity
#5
Ruibo Zhao, Xueyao Liu, Xinyan Yang, Biao Jin, Changyu Shao, Weijia Kang, Ruikang Tang
Chemotherapy-induced cytotoxicity in normal cells and organs triggers undesired lesions. Although targeted delivery is used extensively, more than half of the chemotherapy dose still concentrates in normal tissues, especially in the liver. Enabling normal cells or organs to defend against cytotoxicity represents an alternative method for improving chemotherapy. Herein, rationally designed nanomaterials are used as artificial organelles to remove unexpected cytotoxicity in normal cells. Nanocomposites of gold-oligonucleotides (Au-ODN) can capture intracytoplasmic doxorubicin (DOX), a standard chemotherapy drug, blocking the drug's access into the cell nucleus...
May 15, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29695909/increase-in-spleen-volume-as-a-predictor-of-oxaliplatin-toxicity
#6
Alissar El Chediak, Ali A Haydar, Ayman Hakim, Sarah Abdel Massih, Lara Hilal, Deborah Mukherji, Sally Temraz, Ali Shamseddine
Background: Oxaliplatin is a nonconventional third-generation platinum compound. It is an important chemotherapeutic agent in regimens used in gastrointestinal carcinomas as well as other malignancies. Oxaliplatin toxicity profile includes neurotoxicity, hepatotoxicity, and splenomegaly. The primary aim of this study was to measure the spleen volume of patients on oxaliplatin therapy before and during chemotherapy to detect any increase in splenic size as a biomarker for early oxaliplatin toxicity...
2018: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/29672189/abrogation-of-hepatic-damage-induced-by-anticancer-drug-methotrexate-by-zobo-hibiscus-sabdariffa-extract-supplementation-via-targeting-oxidative-hepatotoxicity-in-rats
#7
Ademola C Famurewa, Abiola M Folawiyo, Michael A Epete, Emeka C Igwe, Paul I Okike, Ekenechukwu K Maduagwuna
Clinical use of methotrexate (MTX) in cancer chemotherapy is limited due to its side effects, notably associated with increased oxidative stress and hepatotoxicity. Zobo is an aqueous extract of Hibiscus sabdariffa known to contain natural antioxidants. The present study investigated the hepatoprotective effect of zobo drink (ZD) on MTX-induced oxidative stress and hepatotoxicity in rats. Rats randomized to control group received distilled water orally; MTX group received intraperitoneal (ip) injection of MTX (20 mg/kg) on day 11; ZD + MTX group was administered ZD (10 ml/kg) for 14 days and was injected with MTX on day 11...
April 19, 2018: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/29621129/plants-and-surgery-the-protective-effects-of-thymoquinone-on-hepatic-injury-a-systematic-review-of-in-vivo-studies
#8
REVIEW
Aysun Tekbas, Jutta Huebner, Utz Settmacher, Uta Dahmen
Multimodal treatment concepts including liver transplantation for hepatocellular carcinoma (HCC), extended resection methods and neoadjuvant chemotherapy for colorectal liver metastasis significantly improve patients’ outcome. However, surgery-induced hepatic ischemia-reperfusion injury (IRI) and chemotherapy-associated hepatotoxicity result in hepatocellular damage and compromised liver function. Activation of common key pathways in ischemic liver and hepatotoxic injury results in oxidative stress, inflammatory responses and apoptosis causing organ damage...
April 5, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29569486/pharmacoepigenetics-in-childhood-acute-lymphoblastic-leukemia-involvement-of-mirna-polymorphisms-in-hepatotoxicity
#9
Angela Gutierrez-Camino, Maitane Umerez, Borja Santos, Idoia Martin-Guerrero, Nagore García de Andoin, Ana Sastre, Aurora Navajas, Itziar Astigarraga, Africa Garcia-Orad
AIM: Hepatotoxicity is one of the most common drug-related toxicities during the treatment of childhood acute lymphoblastic leukemia (ALL). Many genes involved in liver-specific signaling pathways are tightly controlled by miRNAs, and miRNA function could be modulated by SNPs. As a consequence, we hypothesized that variants in miRNAs could be associated with drug-induced hepatotoxicity. METHODS: We analyzed 213 SNPs in 206 miRNAs in a cohort of 179 children with ALL homogeneously treated...
April 1, 2018: Epigenomics
https://www.readbyqxmd.com/read/29564988/detection-of-the-incidence-of-infections-and-acute-biochemical-changes-in-diffuses-large-b-cell-lymphoma-patients-treated-with-cyclophosphamide-doxorubicin-vincristine-and-prednisone-chop-with-and-without-rituximab
#10
Kashif Ali, Ali Akbar Sial, Mirza Tasawer Baig, Saqib Hussain Ansari, Syed Omair Adil, Tahir Sultan Shamsi
AIM AND OBJECTIVES: Acute biochemical changes, hepatotoxicity, nephrotoxicity and frequency of infections are common in diffuse large B-cell Lymphoma patients undergoing Cyclophosphamide, hydroxyrubicin, Oncovin (Vincristine) Prednisolone (CHOP) and Rituximab plus CHOP chemo cycles. Eventually, it leads to prolong hospital stay and suspending the next chemotherapy cycles. Changes in biochemical profile and immunosuppressant effects correlated with dose intensity ratio, the findings of this study will be helpful in choices for the physician to discontinue therapy or delaying treatment...
March 20, 2018: Current Drug Safety
https://www.readbyqxmd.com/read/29530589/cisplatin-induced-gastrointestinal-toxicity-an-update-on-possible-mechanisms-and-on-available-gastroprotective-strategies
#11
REVIEW
Faaiza Shahid, Zeba Farooqui, Farah Khan
Cisplatin (cis-diamminedichloroplatinum [II], CP) is most widely prescribed in chemotherapy and efficaciously treats diverse human cancers, with remission rates > 90% in testicular cancers. However, clinical use of CP is associated with numerous untoward side effects, in particular, at the gastrointestinal level that reduces the therapeutic efficacy of CP and often results in withdrawal of its clinical usage in long term cancer chemotherapy. Substantial strides have been made to identify effective protective strategies against CP-induced nephrotoxicity, hepatotoxicity and ototoxicity...
May 15, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29486335/crocin-attenuates-cyclophosphamide-induced-testicular-toxicity-by-preserving-glutathione-redox-system
#12
Ajay Godwin Potnuri, Lingesh Allakonda, Mangala Lahkar
Chemotherapy induced testicular toxicity is an emerging reason for azoospermia and impotency in males. Cyclophosphamide (CP) is a widely used chemotherapeutic agent to manage neoplastic and non-neoplastic autoimmune diseases. Testicular toxicity along with bladder and hepatotoxicity are its widely reported adverse effects. Crocin (CR) is the digentiobiosyl ester of crocetin, found in the fruits of gardenia (Gardenia jasminoides E.) and dried stigmas of saffron (Crocus sativus L.) possess antioxidant, anti-depressant, anti-tumor and aphrodisiac properties...
May 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29329420/pyrrolidine-dithiocarbamate-reverses-bcl-xl-mediated-apoptotic-resistance-to-doxorubicin-by-inducing-paraptosis
#13
Seok Soon Park, Dong Min Lee, Jun Hee Lim, Dongjoo Lee, Sang Jun Park, Hwan Myung Kim, Seonghyang Sohn, Gyesoon Yoon, Young Woo Eom, Seong-Yun Jeong, Eun Kyung Choi, Kyeong Sook Choi
Elevated Bcl-xL expression in cancer cells contributes to doxorubicin (DOX) resistance, leading to failure in chemotherapy. In addition, the clinical use of high-dose doxorubicin (DOX) in cancer therapy has been limited by issues with cardiotoxicity and hepatotoxicity. Here, we show that co-treatment with pyrrolidine dithiocarbamate (PDTC) attenuates DOX-induced apoptosis in Chang-L liver cells and human hepatocytes, but overcomes DOX resistance in Bcl-xL-overexpressing Chang-L cells and several hepatocellular carcinoma (HCC) cell lines with high Bcl-xL expression...
March 8, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29301090/evaluation-of-therapeutic-effect-of-rice-husk-silica-combined-with-platelets-derived-growth-factor-in-hepatic-veno-occlusive-disease
#14
Eithar K Al Adham, Amal I Hassan, M M Hazem, Ahmed Shebl
Veno- occlusive disease is an important pattern of hepatotoxicity associated with antineoplastic drugs. The study aimed to investigate the possible therapeutic impact of rice husk silica (RHS) nanoparticles combined with a platelet-derived growth factor (PDGF) on the Veno-occlusive disease in liver (VOD) elicited by dactinomycin (DAC) in rats. Forty-eight male Sprague-Dawely rats were classified into six groups, 8 rats each. The first group served as control, the second, animals were infused by intraperitoneal injection with DAC (0...
January 4, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29262297/antiallodynic-and-antihyperalgesic-activity-of-new-3-3-diphenyl-propionamides-with-anticonvulsant-activity-in-models-of-pain-in-mice
#15
Anna Rapacz, Jolanta Obniska, Paulina Koczurkiewicz, Katarzyna Wójcik-Pszczoła, Agata Siwek, Anna Gryboś, Sabina Rybka, Aleksandra Karcz, Elżbieta Pękala, Barbara Filipek
Anticonvulsant drugs are used to treat a wide range of non-epileptic conditions, including chronic pain. The aim of the present experiments was to examine analgesic activity of three new 3,3-diphenyl-propionamides, which had previously demonstrated anticonvulsant activity in the MES (maximal electroshock seizure), scPTZ (subcutaneous pentylenetetrazole) and/or 6Hz (psychomotor seizure) tests in mice. Antinociceptive activity was examined in mouse models of acute pain (the hot plate test) and tonic pain (the formalin test) in mice...
February 15, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29096656/liver-resection-for-hepatocellular-carcinoma-in-patients-with-hematological-malignancies
#16
Hui-Chen Lin, Yang-Shen Yang, Chieh-Lin Jerry Teng, Ching-Hui Shen, Yee-Gee Jan, Shao-Bin Cheng, Cheng-Chung Wu, Yi-Ling Lin, Chu-Chun Huang, Fang-Ku P'eng
BACKGROUND: Improvements in antimetabolite drugs have prolonged the survival of patient with hematological malignancies. However, these drugs may have hepatotoxic side effects and may induce acute liver failure, chronic liver fibrosis, cirrhosis, or even hepatocellular carcinoma (HCC). Although liver resection remains a curative option for HCC, its role in HCC with hematological malignancies has never been fully explored. METHODS: A retrospective review of 1725 patients who underwent curative liver resection for newly diagnosed HCC between 1994 and 2016 was conducted...
November 2, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29095437/metformin-ameliorates-arsenic-trioxide-hepatotoxicity-via-inhibiting-mitochondrial-complex-i
#17
Sunbin Ling, Qiaonan Shan, Peng Liu, Tingting Feng, Xuanyu Zhang, Penghui Xiang, Kangchen Chen, Haiyang Xie, Penghong Song, Lin Zhou, Jimin Liu, Shusen Zheng, Xiao Xu
Arsenic trioxide (ATO) is a well-accepted chemotherapy agent in managing promyelocytic leukemia. ATO often causes severe health hazards such as hepatotoxicity, dermatosis, neurotoxicity, nephrotoxicity and cardiotoxicity. The production of reactive oxygen species, (ROS) play a significant role in ATO-induced hepatotoxicity. The oral hypoglycemic drug, metformin, is considered to be a potential novel agent for chemoprevention in the treatment of cancer. Moreover, metformin has also been shown to have hepatoprotective effects...
November 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28781805/successful-oral-desensitization-with-crizotinib-after-crizotinib-induced-hepatitis-in-an-anaplastic-lymphoma-kinase-rearranged-non-small-cell-lung-cancer-patient-a-case-report
#18
Yuto Yasuda, Yasuyo Nishikawa, Yuichi Sakamori, Makoto Terao, Kentaro Hashimoto, Tomoko Funazo, Takashi Nomizo, Takahiro Tsuji, Hironori Yoshida, Hiroki Nagai, Hiroaki Ozasa, Toyohiro Hirai, Young Hak Kim
Crizotinib is one of the molecularly-targeted agents targeted against anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC). Although its effects appear to be promising, crizotinib may cause adverse effects in patients with ALK-rearranged NSCLC. Hepatic laboratory abnormalities are frequently observed with crizotinib and treatment discontinuation is occasionally required. We herein report the case of a 51-year-old woman diagnosed with relapsed ALK-rearranged NSCLC, who received crizotinib as second-line systemic chemotherapy...
August 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28718673/ameliorative-effect-of-gallic-acid-in-doxorubicin-induced-hepatotoxicity-in-wistar-rats-through-antioxidant-defense-system
#19
Temidayo Olutayo Omobowale, Ademola Adetokunbo Oyagbemi, Uchechukwu Enwiwe Ajufo, Olumuyima Abiola Adejumobi, Olufunke Eunice Ola-Davies, Adeolu Alex Adedapo, Momoh Audu Yakubu
Hepatotoxicity has been found to be one of the main side effects associated with doxorubicin (Dox) administration in cancer therapy. The aim of the present study was to examine the ameliorative effect of gallic acid (GA) in Dox-induced hepatotoxicity. Sixty male Wistar rats of 10 rats per group were used in this study and were randomly divided into 6 experimental groups (A-F). Rats in Group A served as the control group and received distilled water orally for 7 days; Group B was given Dox at 15 mg/kg body weight intraperitoneally (IP) on Day 8...
March 4, 2018: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28656202/ameliorative-efficacy-of-quercetin-against-cisplatin%C3%A2-induced-mitochondrial-dysfunction-study-on-isolated-rat-liver-mitochondria
#20
Mohammad Waseem, Heena Tabassum, Monica Bhardwaj, Suhel Parvez
The present study aimed to investigate the hepatoprotective effects of the bioflavonoid quercetin (QR) on cisplatin (CP)‑induced mitochondrial oxidative stress in the livers of rats, to elucidate the role of mitochondria in CP‑induced hepatotoxicity, and its underlying mechanism. Isolated liver mitochondria were incubated with 100 µg/ml CP and/or 50 µM QR in vitro. CP treatment triggered a significant increase in membrane lipid peroxidation (LPO) levels, protein carbonyl (PC) contents, and a decrease in reduced glutathione (GSH) and non‑protein thiol (NP‑SH) levels...
September 2017: Molecular Medicine Reports
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