Reduced renal blood flow in early cisplatin-induced acute renal failure in the rat

Winston, Jonathan; Safirstein, Robert

doi:10.1152/ajprenal.1985.249.4.f490

Cited by 127 publications

(117 citation statements)

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“…A common adverse side effect of cisplatin treatment is nephrotoxicity. For example, a single intraperitoneal injection of cisplatin (5 mg/kg) induces acute renal failure in a rat model (Winston and Safirstein, 1985). The nephrotoxic effect of cisplatin on the kidney is thought to be mediated in part through the thromboxane A 2 pathway (Jariyawat et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of thromboxane synthase activity modulates bladder cancer cell responses to chemotherapeutic agents

et al. 2007

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Recently, we reported prognostic significance of thromboxane synthase (TXAS) gene expression in invasive bladder cancer. The positive correlation between elevated TXAS expression and shorter patient survival supports a potential role for TXAS-regulated pathways in tumor metastases. In this study, using immunohistochemical analysis, we found an increased expression of TXAS protein in bladder cancer. Treatment of T24 and transitional cell carcinoma TCC-SUP bladder cancer cells with the TXAS inhibitors furegrelate or ozagrel induced an apoptotic effect measured as an increase in caspase-3 activation and cell death, and decreased survivin expression. Pharmacological inhibition of TXAS using the TXAS inhibitor furegrelate increased sensitivity to the chemotherapeutic agents cisplatin and paclitaxel. Molecular inhibition of TXAS expression by siRNA significantly decreased cell growth and migration. In concordance with the pharmacological data, siRNAmediated reduction of TXAS expression increased sensitivity to cisplatin and paclitaxel in T24 and TCC-SUP cells. In summary, the data support a role for the thromboxane A 2 pathway in the pathogenesis of bladder cancer and the potential utility of modulation of this signaling pathway for cancer chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Inhibition of thromboxane synthase activity modulates bladder cancer cell responses to chemotherapeutic agents

et al. 2007

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“…Although cell death in renal tubules is widely recognized, cisplatin also is expected to disrupt vasculature in the kidneys, leading to hypoperfusion or hypoxia (16). This view is supported by direct evidence from recent studies that detected the staining of outer renal medulla and cortex of cisplatin-treated animals by pimonidazole, a hypoxia-specific dye (6).…”

mentioning

confidence: 92%

Cytoprotective Effects of Hypoxia against Cisplatin-Induced Tubular Cell Apoptosis

Wang

Biju

Wang

et al. 2006

Journal of the American Society of Nephrology

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Hypoxia that is caused by vascular defects or disruption is commonly associated with renal diseases. During cisplatin nephrotoxicity, hypoxic regions are identified in the outer medulla and the renal cortex. However, the regulation of cisplatin injury by hypoxia is unclear. Previous work has demonstrated the cytoprotective effects of hypoxia against apoptotic injury. This study further examines the cytoprotective mechanisms in models of cisplatin-induced tubular cell apoptosis. In cultured renal tubular cells, 20 M cisplatin induced approximately 60% apoptosis within 16 h. The rate of apoptosis was suppressed to <20%, when the incubation was conducted under hypoxia (2% O 2 ). Mitochondrial events of apoptosis, namely Bax accumulation and cytochrome c release, also were ameliorated. During cisplatin treatment, cell ATP was maintained in both normoxic and hypoxic cells. Hypoxic incubation lowered extracellular pH, but prevention of the pH decrease did not restore cisplatin-induced apoptosis. The cytoprotective effects of hypoxia also were independent of hypoxia-inducible factor 1 (HIF-1). Cobalt, as hypoxia, activated HIF-1 yet did not suppress cisplatin-induced apoptosis. Moreover, hypoxia suppressed cisplatin-induced apoptosis in HIF-1-deficient mouse embryonic stem cells and renal proximal tubular cells. Conversely, mitochondrial inhibitors, particularly inhibitors of respiration complex III (antimycin A and myxothiazol), mimicked hypoxia in apoptosis suppression. The effects of hypoxia and mitochondrial inhibitors were not additive. It is interesting that both hypoxia and complex III inhibitors ameliorated cisplatin-induced p53 activation. Therefore, the cytoprotective effects of hypoxia are independent of changes in cell ATP, pH, or HIF but may involve mitochondrial inhibition and the suppression of p53.

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“…CP is the inhibitor of desoxyribonucleic acid synthesis (4) and nephrotoxicity of CP seems to be related to reactive oxygen species. Reactive oxygen species, especially the hydroxyl radical, induce lipid peroxidation and cell membrane damage and reduce glomerular filtration rate (GFR) (7)(8)(9). It is reported that CP-induced nephrotoxicity may be ameliorated by scavenging agents such as vitamins E and C, losartan, melatonin, selenium, superoxide dismutase, and erythropoietin (10)(11)(12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Protective Role of Aerobic Exercise Against Cisplatin-Induced Nephrotoxicity in Rats

et al. 2015

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Background: Cisplatin (CP) is a chemotherapy drug and nephrotoxicity is considered as its major side effect. Aerobic exercise is well known as an approach to reduce the side effects of many drugs. Objectives: This study was designed to determine the protective role of aerobic exercise against CP-induced nephrotoxicity. Materials and Methods: Thirty male Wistar rats were randomly divided into four groups. Group I had aerobic exercise on a treadmill one hour per day and five days per week for eight weeks. Then, the exercise protocol was continued for another week, but during this week, the animals also received CP (2.5 mg/kg/day; ip). Group II underwent the same protocol as group I without exercise in the last week during the CP therapy. Groups III and IV were assigned as positive and negative control groups, and were treated with CP and saline without exercise, respectively. Finally, the animals were sacrificed for the biochemical measurement and tissue histopathology investigation. Results: CP alone without exercise increased serum levels of blood urea nitrogen (BUN), creatinine (Cr), and malondialdehyde (MDA); and kidney nitrite level, while treadmill exercise in group I significantly ameliorated these parameters (P < 0.05). Kidney and serum levels of MDA and nitrite did not alter significantly. Also, the severity of kidney tissue damage decreased significantly in groups I and II (P < 0.05). Conclusions: Aerobic exercise may reduce CP-induced nephrotoxicity with a favorable effect on renal function by increasing activation of antioxidant system.

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Reduced renal blood flow in early cisplatin-induced acute renal failure in the rat

Cited by 127 publications

References 0 publications

Inhibition of thromboxane synthase activity modulates bladder cancer cell responses to chemotherapeutic agents

Inhibition of thromboxane synthase activity modulates bladder cancer cell responses to chemotherapeutic agents

Cytoprotective Effects of Hypoxia against Cisplatin-Induced Tubular Cell Apoptosis

Protective Role of Aerobic Exercise Against Cisplatin-Induced Nephrotoxicity in Rats

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