Effects of cisplatin on urinary thromboxane B2 excretion*

Blöchl-Daum, Brigitte; Pehamberger, Hubert; Kurz, Christine; Kyrle, Paul-Alexander; Wagner, Oswald; Müller, Markus; Monitzer, Brigitte; Eichler, Hans‐Georg

doi:10.1016/0009-9236(95)90055-1

Cited by 17 publications

(12 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results are in good agreement with those of previous reports [22,23]. Several reports demonstrate different mechanisms involved in the CDDP-induced nephrotoxicity including protein kinase C activation [24], elevation of caspase-3 activity resulting in renal cell apoptosis [25], enhancement of intrarenal synthesis of thromboxane A 2 [26] and dyslipidemia [27].…”

Section: Discussionsupporting

confidence: 82%

Protection Effects of Taurine Supplementation against Cisplatin-Induced Nephrotoxicity in Rats

Saad

Al-Rikabi²

2002

Chemotherapy

View full text Add to dashboard Cite

Backgound: Taurine, which is the major intracellular free β-amino acid, is known to be an antioxidant and a membrane-stabilizing agent. This study was designed to investigate the protective role of taurine supplementation against cisplatin-induced nephrotoxicity. Methods: Male Wistar rats were divided into six groups and treated as follows: (1) saline-treated control drinking tap water, (2) saline-treated plus taurine-supplemented (1.5% taurine in the drinking water), (3) saline-treated plus taurine-depleted (3% β-alanine in the drinking water), (4) cisplatin-treated, CDDP 6 mg/kg intraperitoneally, (5) taurine-supplemented plus CDDP-treated and (6) taurine-depleted plus CDDP-treated. Rats were sacrificed 7 days after CDDP treatment, and serum as well as kidneys were isolated and analyzed. Results: CDDP-treated rats showed increased kidney weight as a percentage of total body weight, serum creatinine and BUN levels and decreased serum albumin and calcium levels. Also, CDDP treatment resulted in a depletion of kidney GSH content, a reduction in the kidney glutathione peroxidase (GSH-Px) activity and increased kidney MDA production level. Taurine supplementation attenuated CDDP-induced nephrotoxicity which was manifested by jeopardizing the elevation in serum creatinine and BUN levels and the reduction in serum albumin and calcium levels. Moreover, taurine supplementation restored kidney GSH content and GSH-Px activity and reduced platinum accumulation and MDA production levels in the kidney tissue following CDDP treatment. Histopathological examination of the kidney of CDDP-treated rats revealed tubular atrophy, tubular necrosis and desquamation of renal tubular cells. However, taurine supplementation protected against CDDP-induced histopathological changes. Conclusions: The data suggest that taurine supplementation effectively attenuates the accumulation of platinum within kidney tissue and counteracts the deleterious effect of CDDP on the renal tubular function.

show abstract

Section: Discussionsupporting

confidence: 82%

Protection Effects of Taurine Supplementation against Cisplatin-Induced Nephrotoxicity in Rats

Saad

Al-Rikabi²

2002

Chemotherapy

View full text Add to dashboard Cite

show abstract

“…Cisplatin has been used as a chemotherapeutic agent for the treatment of bladder cancer (32), but its use is associated with renal toxicity (33) and increased renal synthesis of thromboxane A 2 (34,35). Increased intrarenal synthesis of TP has been shown to be associated with impaired function (36,37).…”

Section: Discussionmentioning

confidence: 99%

Novel Role of Thromboxane Receptors β Isoform in Bladder Cancer Pathogenesis

et al. 2008

View full text Add to dashboard Cite

These studies were undertaken to determine the potential role of thromboxane receptors (TP) in bladder cancer. The data reported herein show that expression of the TP-B receptor protein is increased in tissue obtained from patients with bladder cancer and associated with a significantly poorer prognosis (P < 0.005). Bladder cancer cell lines express the TP-B isoform, unlike immortalized nontransformed urothelial cells (SV-HUC) that express only the TP-A isoform. TP-B receptor expression, but not TP-A, promoted cell proliferation, migration, and invasion in vitro, and also resulted in malignant transformation of SV-HUC cells in vivo. Agonist-mediated phosphorylation of extracellular signal-regulated kinase and FAK was dependent on the expression of TP-B. Furthermore, TP-B mediated multiple biological effects by signaling through either G-protein A subunit 12 or B-arrestin 2. Treatment of mice with the TP receptor antagonist GR32191, alone or in combination with cisplatin, significantly delayed tumor onset and prolonged survival of mice transplanted with TCC-SUP bladder cancer cells compared with vehicle or cisplatin alone. These results support the model that the TP-B receptor isoform plays a unique role in bladder cancer progression and its expression may have predictive value and provide a novel therapeutic target. [Cancer Res 2008;68(11):4097-104]

show abstract

“…Clinically, it was reported that urinary excretion of TXB 2 was increased 4.5-fold during and immediately after cisplatin infusion in patients treated for various malignancies. 31 TXA 2 production was also observed following treatment with other cytotoxic drugs such as gentamicin 32 and cyclosporine. 33 This further supports the clinical relevance of our findings and implies that not only might a defective TP-Siva axis contribute to apoptosis resistance in tumours, but a functional TP-Siva axis in surrounding normal tissues and organs might also contribute to the toxicity of the chemotherapeutic treatment.…”

Section: Discussionmentioning

confidence: 92%

Thromboxane A2 modulates cisplatin-induced apoptosis through a Siva1-dependent mechanism

Iorio-Morin

Germain

et al. 2012

Cell Death Differ

View full text Add to dashboard Cite

Thromboxane A 2 (TXA 2 ) is an important lipid mediator whose function in apoptosis is the subject of conflicting reports. Here, a yeast two-hybrid screen for proteins that interact with the C-terminus of the TXA 2 receptor (TP) identified Siva1 as a new TP-interacting protein. Contradictory evidence suggests pro-and anti-apoptotic roles for Siva1. We show that a cisplatin treatment induces TXA 2 synthesis in HeLa cells. We demonstrate that endogenous TP stimulation promotes cisplatin-induced apoptosis of HeLa cells and that such modulation requires the expression of Siva1, as evidenced by inhibiting its endogenous expression using siRNAs. We reveal that, upon stimulation of TP, degradation of Siva1 is impeded, resulting in an accumulation of the protein, which translocates from the nucleus to the cytosol. Translocation of Siva1 correlates with its reduced interaction with Mdm2 (an inhibitor of p53 signalling), as well as with its increased interaction with TRAF2 and XIAP (known to enhance pro-apoptotic signalling). Our data provide a model that reconciles the pro-and anti-apoptotic roles that were reported for Siva1 and identify a new mechanism for promoting apoptosis by G protein-coupled receptors. Our findings may have implications in the use of cyclo-oxygenase inhibitors during cisplatin chemotherapy and might provide a target to reduce cisplatin toxicity on non-cancerous tissues.

show abstract

Effects of cisplatin on urinary thromboxane B2 excretion*

Cited by 17 publications

References 8 publications

Protection Effects of Taurine Supplementation against Cisplatin-Induced Nephrotoxicity in Rats

Protection Effects of Taurine Supplementation against Cisplatin-Induced Nephrotoxicity in Rats

Novel Role of Thromboxane Receptors β Isoform in Bladder Cancer Pathogenesis

Thromboxane A2 modulates cisplatin-induced apoptosis through a Siva1-dependent mechanism

Contact Info

Product

Resources

About