A novel in vitro system, the integrated discrete multiple organ cell culture (IdMOC) system, for the evaluation of human drug toxicity: comparative cytotoxicity of tamoxifen towards normal human cells from five major organs and MCF-7 adenocarcinoma breast cancer cells

Li, Albert P.; Bode, Chris; Sakai, Yumiko

doi:10.1016/j.cbi.2004.09.010

Cited by 105 publications

(74 citation statements)

References 27 publications

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“…Tamoxifen induces free radicals production in renal tissue, and at the same time decreases its ability to detoxify reactive oxygen species. TM intoxication leads to disruption of the activity of glutathione metabolizing and antioxidant enzymes [5].…”

Section: Discussionmentioning

confidence: 99%

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The role of vitamin C in alteration of enzymes responsible of energy metabolism induced by administration of tamoxifen to mouse

Zuhair¹,

Al-Amri²

2011

ABC

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Tamoxifen is a synthetic non-steroidal ant estrogen. It was suggested to study the role of vitamin C in alteration of enzymes responsible of energy metabolism induced by administration of tamoxifen to mouse. The effect of tamoxifen and tamoxifen with vitamin C on some activity of enzymes in the mice representing glycolytic, gluconeogenic and glycogenolytic pathway and also, liver function enzymes represented by aspartate aminotransferase (AST), alanine amino-transferase (ALT), acid phosphatase (ACP) and alkaline phosphatase (ALP) were studied. The present results showed that a significant (p < 0.001) increase in glycolytic enzymes (HK, PK, GPI and PFK), gluconeogenic enzymes, G-6-Pase, acid phosphatase (ACP), alkaline phosphatase (ALP) and glucose, were observed in treated groups, while LDH, glycogen phosphorylase, AST and ALT enzymes activities showed significant (p < 0.01) reduction. The present results also, showed that significant reduction in glycogen, total protein, total cholesterol, uric acid, urea, and creatinine in treated mice as compared to the normal healthy control group. However, normal control mice treated with tamoxifen and vitamin C showed no side effects of most parameters compared to the normal healthy control group. It was concluded that vitamin C may prevent tamoxifen-induced testes toxicity in mice.

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Section: Discussionmentioning

confidence: 99%

“…Also, tamoxifen caused cytotoxicity on primary cells from human multiple organs: Kidney, liver and lung [5].…”

Section: Introductionmentioning

confidence: 99%

The role of vitamin C in alteration of enzymes responsible of energy metabolism induced by administration of tamoxifen to mouse

Zuhair¹,

Al-Amri²

2011

ABC

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“…Cell culture systems have been extensively used to evaluate toxicity of drugs in specific organs. 13 In vitro cell culture techniques that mimic the in vivo state of cell lines maintain similar levels of marker enzymes of metabolism exhibited by freshly isolated cells. 14 …”

Section: Introductionmentioning

confidence: 99%

The Effects ofSyzygium aromaticum-Derived Oleanolic Acid on Kidney Function of Male Sprague–Dawley Rats and on Kidney and Liver Cell Lines

et al. 2012

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Studies indicate that Syzygium spp-derived oleanolic acid (OA) enhances renal function of streptozotocin (STZ)-induced diabetic rats as evidenced by its reversal of the previously reported inability of the kidney to excrete Na þ in these animals. We postulated that OA influences Na þ excretion in the proximal tubule, the site where two-thirds of filtered NaCl is reabsorbed through a process mediated by transport proteins. Therefore, the study investigated the effects of OA on proximal tubular Na þ handling in male Sprague-Dawley rats using renal lithium clearance (C Li ). Renal C Li has been used widely in animal and clinical studies to assess proximal tubular function. Sub-chronic doses of OA were administered to rats twice every third day for 5 weeks. Rats treated with deionized water served as control animals. Cytotoxicity of OA on kidney and liver cell lines was assessed by the MTT and comet assays. OA increased Na þ excretion of conscious male Sprague-Dawley rats from week 3 to week 5. By the end of the 5-week experimental period, OA treatment significantly reduced (p < 0.05) plasma creatinine concentration of STZ-induced diabetic rats with a concomitant elevation in glomerular filtration rate (GFR). Acute OA infusion was also associated with increases in fractional excretion of sodium (FE Na ) and lithium (FE Li ) in anesthetized rats in the absence of significant changes in GFR. The MTT assay studies demonstrated that OA increased the metabolic activity of kidney and liver cell lines. Taken together with previous observations, this study implicates the proximal tubule in OA-evoked increases in urinary Na þ output.

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“…The multiple organ interaction is not covered by the TACIT approach 8 using a single cell type, as the initiating events may include effects of a toxicant on a nontarget cell. To overcome this deficiency, we have developed the IdMOC (Independent Discrete Multiple Organ Co-culture) system ( [42][43][44] ). The IdMOC allows the co-culturing of cells from different organs as physically separated cultures that are interconnected by an overlying medium, akin to the blood circulation connecting the multiple organs in the human body (Fig.…”

Section: In Vitro Experimental Model For Multiple Organ Interactions:mentioning

confidence: 99%

Critical Human Hepatocyte-Based In Vitro Assays for the Evaluation of Adverse Drug Effects

Li¹

2011

Drug Discovery and Development - Present and Future

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A novel in vitro system, the integrated discrete multiple organ cell culture (IdMOC) system, for the evaluation of human drug toxicity: comparative cytotoxicity of tamoxifen towards normal human cells from five major organs and MCF-7 adenocarcinoma breast cancer cells

Cited by 105 publications

References 27 publications

The role of vitamin C in alteration of enzymes responsible of energy metabolism induced by administration of tamoxifen to mouse

The role of vitamin C in alteration of enzymes responsible of energy metabolism induced by administration of tamoxifen to mouse

The Effects ofSyzygium aromaticum-Derived Oleanolic Acid on Kidney Function of Male Sprague–Dawley Rats and on Kidney and Liver Cell Lines

Critical Human Hepatocyte-Based In Vitro Assays for the Evaluation of Adverse Drug Effects

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