Doxorubicin- and Daunorubicin-Glutathione Conjugates, but Not Unconjugated Drugs, Competitively Inhibit Leukotriene C4Transport Mediated byMRP/GS-XPump

Priebe, Waldemar; Krawczyk, Marta; Kuo, M. Tien; Yamane, Yoshio; Savaraj, Niramol; Ishikawa, Toshihisa

doi:10.1006/bbrc.1998.8887

Cited by 70 publications

(39 citation statements)

References 18 publications

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“…35,36) The GSH is thought to be associated with the efflux system of DOX and CDDP through ATP-binding cassette transporters (ABCs), such as canalicular multispecific organic anion transporter (cMOAT), and multidrug resistance-associated protein 1 (MRP1). 27,[37][38][39][40][41] Depletion of intracellular GSH using buthionine sulfoximine (BSO) causes a decrease in the efflux activity of DOX and CDDP, reducing the drug resistance of cancer cells. 41,42) We previously reported that GSTπ forms a CDDP-GSH adduct which is transported outside the cells, 25) and the efflux activity of CDDP is elevated in cancer cells resistant to CDDP.…”

Section: Discussionmentioning

confidence: 99%

Significance of Nuclear Glutathione S‐Transferase π in Resistance to Anti‐cancer Drugs

Goto

Kamada

Soh

et al. 2002

Japanese Journal of Cancer Research

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Section: Discussionmentioning

confidence: 99%

Significance of Nuclear Glutathione S‐Transferase π in Resistance to Anti‐cancer Drugs

Goto

Kamada

Soh

et al. 2002

Japanese Journal of Cancer Research

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“…Among the ABC transporters, the prognostic significance of MDR1/P-glycoprotein as an indicator of failure of chemotherapy and a poor outcome has been demonstrated in a number of clinical studies. 62,63) MRP1 transports anticancer drugs such as etoposide, doxorubicin, and vincristine [64][65][66] and acts as a drug-efflux pump, rendering cancer cells resistant to cytostatic drugs. 44) We observed a marked increase in the expression levels of Mdr1b and Mrp1 mRNA following the administration of fatfree TPN, whereas no increase was noted following the administration of fat-containing TPN.…”

Section: Clinical Implications Of Soybean Oil-con-taining Tpnmentioning

confidence: 99%

Soybean Oil Fat Emulsion to Prevent TPN-Induced Liver Damage: Possible Molecular Mechanisms and Clinical Implications

Nishimura

Yamaguchi

Naito

et al. 2006

Biological & Pharmaceutical Bulletin

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INTRODUCTIONTotal parenteral nutrition (TPN), which is recognized as one method for parenteral hyperalimentation, has been found to be an effective and relatively safe method for supplying energy and nutrients to surgical patients. Following improvements in parenteral regimens including vitamins and trace elements and in catheter techniques to reduce the septic complications associated with TPN, TPN has been widely employed to provide complete nutritional support and therapeutic benefits in a variety of pathophysiological settings in which patients are unable to eat. However, TPN-induced hepatobiliary dysfunction, which was first described by Peden et al.,1) has been recognized as a cause of severe morbidity and a life-threatening complication of TPN, especially in neonates and infants. Hepatic dysfunction with steatosis is the most common complication associated with fat-free TPN in adults, and cholestasis is more common in infants.2,3) Recently, the 3-component infusion solution containing amino acids, glucose, and soybean oil emulsion, GA-1080 (MIXID ® , Otsuka Pharmaceutical Factory, Inc.; Tokushima, Japan), has been demonstrated to be effective in overcoming such hepatic morbidity in clinical studies.4) Intravenous fat emulsions, especially soybean oil, are now available as a source of essential fatty acids in patients receiving TPN, and the "three-in-one" solution GA-1080 has been found to be clinically safe, stable, and economical. However, the multifactorial pathogenesis of TPN-induced hepatic dysfunction remains unclear, and the molecular mechanisms by which GA-1080 prevents hepatic dysfunction have not yet been identified.We have recently developed an infant rat model of hepatobiliary dysfunction.5) Using this animal model, we have clearly demonstrated the metabolic complications in the liver that may occur due to the excessive administration of fat-free TPN in infant rats. Furthermore, we have shown that including fat in the TPN regimen is very important in preventing TPN-induced hepatic dysfunction. In this review, we describe the molecular mechanisms and the clinical implications of soybean oil in TPN solutions in avoiding the hepatic complications associated with parenteral nutrition. INFANT RAT TPN MODEL WITH HEPATOBILIARY DYSFUNCTIONSince the first studies of TPN in animal models conducted in 1968 by Dudrick et al.,6) it has been known that only a limited number of species (such as the dog, cat, rabbit, and guinea pig) can tolerate the surgical procedures required for TPN, and few studies have employed rats as an animal model for TPN. In 1981, Tashiro and Meng 7) were the first to report a technique for long-term TPN in unrestrained weanling or infant (3-week-old) rats, thus establishing an animal model for pediatric TPN. Numerous studies have focused on the optimal TPN composition in mature rats, but few have addressed this issue in infant rats.We have recently developed an infant rat model with hepatic dysfunction and steatosis induced by overdose of fatfree TPN. 5) After 30 infant (3-week-ol...

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“…The two highest affinity substrates identified to date are the proinflammatory cysteinyl leukotriene C 4 (LTC 4 ) (10 -12) and the GSHconjugated epoxide of the potent mutagen, aflatoxin B 1 (13). In addition, MRP1 has been shown to be capable of direct active transport of conjugated bile salts (14) and nonpeptide hormones as well as in vitro synthesized drug conjugates such as doxorubicin-SG (15) and VP-16-glucuronide (14). MRP1 can also transport oxidized glutathione with low affinity but relatively high capacity (16,17).…”

Section: Multidrug Resistance Protein 1 (Mrp1)mentioning

confidence: 99%

Comparison of the Functional Characteristics of the Nucleotide Binding Domains of Multidrug Resistance Protein 1

Gao¹,

Cui²,

Loe³

et al. 2000

Journal of Biological Chemistry

173

259

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Multidrug Resistance Protein 1 (MRP1) 1 is a member of the ATP-binding cassette (ABC) superfamily of transmembrane transporters that has been shown to confer resistance to a variety of natural product type drugs (1-6). The drug resistance phenotype conferred by MRP1 is similar to that resulting from overexpression of P-glycoprotein (P-gp) (reviewed in Refs. 7-9) and is typically associated with an ATP-dependent decrease in drug accumulation and an increase in drug efflux (4, 6). Although both ABC proteins can function as energy-dependent efflux pumps for a range of natural product type drugs, there is very limited primary structure similarity between them, and phylogenetic analyses suggest that they evolved from different ancestral proteins. There is also considerable evidence that the mechanisms by which MRP1 and P-gp transport drugs are different (reviewed in Ref. 8).In addition to its ability to confer multidrug resistance, MRP1, unlike P-gp, has been shown by in vitro studies using inside-out membrane vesicles to transport a structurally diverse array of organic, anionic conjugates (reviewed in Ref. 9). These include GSH-, glucuronide-, and sulfate-conjugated aliphatic, prostanoid, and heterocyclic compounds. The two highest affinity substrates identified to date are the proinflammatory cysteinyl leukotriene C 4 (LTC 4 ) (10 -12) and the GSH-

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Doxorubicin- and Daunorubicin-Glutathione Conjugates, but Not Unconjugated Drugs, Competitively Inhibit Leukotriene C4Transport Mediated byMRP/GS-XPump

Cited by 70 publications

References 18 publications

Significance of Nuclear Glutathione S‐Transferase π in Resistance to Anti‐cancer Drugs

Significance of Nuclear Glutathione S‐Transferase π in Resistance to Anti‐cancer Drugs

Soybean Oil Fat Emulsion to Prevent TPN-Induced Liver Damage: Possible Molecular Mechanisms and Clinical Implications

Comparison of the Functional Characteristics of the Nucleotide Binding Domains of Multidrug Resistance Protein 1

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