Azo reduction of sulphasalazine in healthy volunteers.

Houston, J. Brian; Day, J; Walker, Jon

doi:10.1111/j.1365-2125.1982.tb01997.x

Cited by 31 publications

(23 citation statements)

References 10 publications

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“…Although the present study utilized DOX as an example for underlining the potential utility of SASP as a sensitizing agent in combination chemotherapy, it is likely that SASP can be used in combination with a multitude of cytotoxic agents whose actions are adversely affected by intracellular GSH content and MRP activity. While oral administration of SASP would lead to its degradation by intestinal bacteria to sulfapyridine and 5-aminosalicylic acid, and hence to loss of x c --inhibitory activity [16] , this problem could likely be reduced by oral administration of SASP in combination with antibiotics, reported to diminish bacterial cleavage of the drug [36] . The fact that SASP is a relatively nontoxic, inexpensive and FDA-approved drug should facilitate its clinical use as a new anticancer agent.…”

Section: Discussionmentioning

confidence: 99%

Sulfasalazine-Induced Reduction of Glutathione Levels in Breast Cancer Cells: Enhancement of Growth-Inhibitory Activity of Doxorubicin

Narang

Pauletti²,

Gout³

et al. 2007

Chemotherapy

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Background: We previously showed that the anti-inflammatory drug, sulfasalazine (salicylazosulfapyridine, SASP), can arrest proliferation of MCF-7 and MDA-MB-231 mammary cancer cells by inhibiting uptake of cystine via the x_c^– cystine/glutamate antiporter. Here we examined SASP with regard to reduction of cellular glutathione (GSH) levels and drug efficacy-enhancing ability. Methods: GSH levels were measured spectrophotometrically. Cellular drug retention was determined with ³H-labeled methotrexate, and drug efficacy with a colony formation assay. Results: Incubation of the mammary cancer cells with SASP (0.3–0.5 mM) led to reduction of their GSH content in a time- and concentration-dependent manner. Similar to MK-571, a multidrug resistance-associated protein inhibitor, SASP increased intracellular accumulation of methotrexate. Preincubation of cells with SASP (0.3 mM) significantly enhanced the potency of the anticancer agent doxorubicin (2.5 nM). Conclusions: SASP-induced reduction of cellular GSH levels can lead to growth arrest of mammary cancer cells and enhancement of anticancer drug efficacy.

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Section: Discussionmentioning

confidence: 99%

Sulfasalazine-Induced Reduction of Glutathione Levels in Breast Cancer Cells: Enhancement of Growth-Inhibitory Activity of Doxorubicin

Narang

Pauletti²,

Gout³

et al. 2007

Chemotherapy

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“…For example, a specific intestinal bacteria Eggerthella lenta has the genetic machinery needed to inactivate the cardiac glycoside digoxin, so antibiotic administration increases serum digoxin concentrations (Lindenbaum et al, 1981;Saha et al, 1983). Bacteria in the colon cleave the prodrug sulfasalazine to 5-aminosalicylic acid (an anti-inflammatory drug) and sulfapyridine (an antibiotic), so ampicillin administration decreases the concentration of sulfapyridine in circulation (Houston et al, 1982). Hepatic phase-1 drug-metabolizing enzymes perform oxidation, reduction, and hydrolysis reactions of drugs, and phase-2 drug-metabolizing enzymes perform conjugation reactions.…”

Section: Introductionmentioning

confidence: 99%

RNA-Seq Quantification of Hepatic Drug Processing Genes in Germ-Free Mice

2015

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Intestinal bacteria have been shown to be important in regulating host intermediary metabolism and contributing to obesity. However, relatively less is known about the effect of intestinal bacteria on the expression of hepatic drug-processing genes in the host. This study characterizes the expression of hepatic drug-processing genes in germ-free (GF) mice using RNA-Seq. Total RNA were isolated from the livers of adult male conventional and GF C57BL/6J mice (n = 3 per group). In the livers of GF mice, the mRNA of the aryl hydrocarbon receptor target gene Cyp1a2 was increased 51%, and the mRNA of the peroxisome proliferator-activated receptor a (PPARa) target gene Cyp4a14 was increased 202%. Conversely, the mRNA of the constitutive androstane receptor (CAR) target gene Cyp2b10 was decreased 57%, and the mRNA of the pregnane X receptor target gene Cyp3a11 was decreased 87% in GF mice. Although other non-Cyp phase-1 enzymes in the livers of GF mice were only moderately affected, there was a marked down-regulation in the phase-2 enzymes glutathione S-transferases p1 and p2, as well as a marked up-regulation in the major bile acid transporters Na + -taurocholate cotransporting polypeptide and organic aniontransporting polypeptide 1b2, and the cholesterol transporter ATPbinding cassette transporter Abcg5/Abcg8. This study demonstrates that intestinal bacteria regulate the expression of a large number of drug-processing genes, which suggests that intestinal bacteria are responsible for some individual differences in drug responses.

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“…However, following colonic delivery these prodrugs must also undergo bacterial azoreduction before releasing 5-ASA. Although this process is usually highly efficient it may be considerably impaired by both rapid transit (van Hees et al, 1979) and antibiotic exposure (Houston et al, 1982), and is therefore a further potential source of reduced bioavailability.…”

Section: Discussionmentioning

confidence: 99%

Delayed‐release mesalazine (5‐aminosalicylic acid): coat dissolution and excretion in ileostomy subjects.

Riley

Tavares

Bennett

et al. 1988

Brit J Clinical Pharma

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Medicine and Dentistry, London and 2Leigh Infirmary, Leigh 1 Delayed-release mesalazine has been formulated to deliver 5-aminosalicylic acid to the colon. We have therefore studied the ileostomy excretion and coat dissolution of this preparation. 2 Following ingestion of a single tablet 88% (range 69-114%) of the 400 mg dose appeared unchanged in the ileosomy effluent over the subsequent 12 h. 3 Ileostomy effluent pH appeared to be a major determinant of 5-aminosalicylic acid release. 4 In vitro studies revealed rapid coat dissolution above pH 7.0, slow dissolution between pH 6.0 and 7.0 and non-dissolution at pH 2.0 and 4.0.

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Azo reduction of sulphasalazine in healthy volunteers.

Cited by 31 publications

References 10 publications

Sulfasalazine-Induced Reduction of Glutathione Levels in Breast Cancer Cells: Enhancement of Growth-Inhibitory Activity of Doxorubicin

Sulfasalazine-Induced Reduction of Glutathione Levels in Breast Cancer Cells: Enhancement of Growth-Inhibitory Activity of Doxorubicin

RNA-Seq Quantification of Hepatic Drug Processing Genes in Germ-Free Mice

Delayed‐release mesalazine (5‐aminosalicylic acid): coat dissolution and excretion in ileostomy subjects.

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