Cyclosporin Treatment in Rheumatoid Arthritis is Associated with an Increased Serum Activity of β-Glucuronidase

Falkenbach, A.; Wigand, R.; Unkelbach, U.; Jörgens, K; Martinovic, A.; Scheuermann, Ernst; Seiffert, U. B.; Kaltwasser, J. P.

doi:10.3109/03009749309095120

Cited by 11 publications

(5 citation statements)

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“…CsA and its metabolites are mainly eliminated via bile (Christians et al, 1991), and an apparent rise with CsA in ␤-glucuronidase activity was seen in the renal tissue in rats (Mohamadin et al, 2005) and human serum (Falkenbach et al, 1993). The C max of unconjugated silibinin in bile was decreased from 242 Ϯ 55 to 37 Ϯ 9.1 g/ml, which reduced the bile elimination of unconjugated silibinin.…”

Section: Discussionmentioning

confidence: 97%

Hepatobiliary Excretion of Silibinin in Normal and Liver Cirrhotic Rats

Wu¹,

Lin

Hung

et al. 2007

Drug Metab Dispos

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ABSTRACT:Silibinin is the main biologically active flavonolignan extracted from the seeds and fruits of milk thistle and has potential efficacy in the treatment of liver disease. The aim of the present study was to examine the hepatobiliary excretion of silibinin and its effect on dimethylnitrosamine (DMN)-induced liver cirrhosis. The experiments were divided into five groups: 10, 30, and 50 mg/kg silibinin alone, 30 mg/kg silibinin coadministered with cyclosporin A (CsA), and 50 mg/kg silibinin with liver cirrhosis induced by DMN. The data indicated that silibinin had dose-related pharmacokinetics in the dose ranges of 10 to 50 mg/kg. All of the unconjugated or total (unconjugated ؉ conjugated) silibinin concentrations in the bile were significantly higher than those in plasma at the sampling time points at each dose, suggesting active hepatobiliary excretion. When coadministered with CsA, the area under the concentration versus time curve (AUC) in bile was significantly decreased. This result suggested that the active silibinin efflux might be partially inhibited by P-glycoprotein. In the DMN-induced liver cirrhotic rats, the AUC of plasma unconjugated silibinin was reduced by 53%; however, total silibinin was increased by 182%. These results together suggest that the phase II conjugative reaction of silibinin was blocked by treatment with DNM.

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Section: Discussionmentioning

confidence: 97%

Hepatobiliary Excretion of Silibinin in Normal and Liver Cirrhotic Rats

Wu¹,

Lin

Hung

et al. 2007

Drug Metab Dispos

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“…as shown in Figure 5, since β-glucuronidase is present only in lysosomes and its activity was taken as a measure of lysosomal stability inorder to arrive at an effective dose of KA. Moreover, Falkembach et al speculate that the β-glucuronidase in serum/plasma may be a marker of intra-articular macrophage activity and would be used as an early indicator of the effectiveness of diseasemodifying drugs in RA patients (Falkenback et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic effect of Kalpaamruthaa, a herbal preparation on adjuvant induced arthritis in wistar rats

2008

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The present study was performed in order to establish the efficacy of Kalpaamruthaa (KA), a modified indigenous Siddha preparation in adjuvant induced arthritic rat (AIA) model with reference to mediators of inflammation (lysosomal enzymes) and its effect on proteoglycans. Albino rats of Wistar strain were divided into seven Groups of six animals each. Arthritis was induced to rats by subcutaneous injection of 0.1 ml of Complete Freund's Adjuvant into the plantar surface of the left hind paw. Group I served as normal control rats receiving 0.5 ml of olive oil as vehicle, Group II arthritic rats served as induced-untreated and Group III (50 mg/kg), Group IV (100 mg/kg), Group V (150 mg/kg), Group VI (200 mg/kg) and Group VII (250 mg/kg) were KA treated rats at different dose levels orally in 0.5 ml of olive oil from 14(th) day of adjuvant injection and was terminated on day 28. Animals were then sacrificed on the day 29, blood was collected, liver and kidney were dissected out, washed and 10% homogenates were prepared. The activities of lysosomal enzymes (beta-glucuronidase, beta-galactosidase, acid phosphatase, beta-N-acetyl glucosaminidase and cathepsin-D), aminotransferases (alkaline phosphatase, aspartate and aminotransferases) and levels of plasma protein bound carbohydrate components of glycoproteins were determined and were found to be elevated in arthritic rats when compared to control animals. After administration of KA, the activities of lysosomal enzymes, aminotransferases and protein-bound carbohydrate component levels were significantly normalized. The data obtained evidently indicate that Kalpaamruthaa is effective at the dose of 150 mg/kg b.wt. in AIA and plays an important role in lysosomal membrane stabilization. This was further confirmed by radiological, histological and electron microscopic studies.

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“…Serum GUS levels can serve as biomarkers for cancer diagnosis [39]. In addition, abnormal serum GUS levels are associated with several diseases, including epilepsy [40], diabetes mellitus [41] and liver disease [42,43]. To evaluate the potential application and detection accuracy in a clinical setting, we used the DCM-βGlcA probe to detect GUS in human serum of both healthy people and cancer patients and compared the results with those obtained using a commercially available GUS ELISA kit.…”

Section: Detection Of Gus In Human Serum Samplesmentioning

confidence: 99%

Highly sensitive light-up near-infrared fluorescent probe for detection and imaging of β-glucuronidase in human serum, living cells and tumor-bearing mice

Zhou

Wang

et al. 2021

Sci. China Mater.

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β-Glucuronidase (GUS) plays a key role in tumor initiation, metastasis, and progression, and thus, has been proposed as a promising cancer biomarker. In this study, we designed an enzyme-activatable near-infrared (NIR) fluorescent probe (DCM-βGlcA) for the rapid and accurate detection of GUS activity in vitro, in vivo and ex vivo. The DCM-βGlcA was prepared by linking a glucuronic acid residue to dicyanomethylene-4H-pyran (DCM). This probe exhibited significant light-up NIR fluorescent signals at 680 nm after reacting with GUS and the Stokes shift could reach 150 nm. The DCM-βGlcA showed a high sensitivity toward GUS and an excellent linear relationship at concentrations ranging between 0 and 4 U L −1 (R 2 = 0.9974) with the limit of detection as low as 0.19 U L −1 . We used the DCM-βGlcA to identify GUS serum levels in both cancer patients and healthy individuals with a similar accuracy as that of an enzyme-linked immunosorbent assay (ELISA) while being easier and faster to perform. Moreover, the DCM-βGlcA was used for tracking endogenous GUS in living cells, thereby discriminating GUSoverexpressed liver cancer from normal cells. Additionally, the DCM-βGlcA was able to detect and image endogenous GUS in liver cancer tissue and tumor-bearing mouse models. These findings demonstrate the potential of the DCM-βGlcA as a promising tool for detecting and monitoring GUS activity in preclinical applications.

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Cyclosporin Treatment in Rheumatoid Arthritis is Associated with an Increased Serum Activity of β-Glucuronidase

Cited by 11 publications

References 4 publications

Hepatobiliary Excretion of Silibinin in Normal and Liver Cirrhotic Rats

Hepatobiliary Excretion of Silibinin in Normal and Liver Cirrhotic Rats

Therapeutic effect of Kalpaamruthaa, a herbal preparation on adjuvant induced arthritis in wistar rats

Highly sensitive light-up near-infrared fluorescent probe for detection and imaging of β-glucuronidase in human serum, living cells and tumor-bearing mice

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