The influence of cyclosporine on lipid peroxidation and superoxide dismutase in adriamycine nephropathy in rats

Zima, Tomáš; Tesař, Vladimı́r; Stípek, S; Crkovská, J; Těmínová, Jana; Plátenı́k, Jan; Rychlík, Ivan; Merta, M; Němeček, Karel; Kameníková, L

doi:10.1016/s0378-4274(96)80359-6

Cited by 3 publications

(5 citation statements)

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“…The toxicity also reflects renal‐tubular injury, as indicated by the increased levels of urinary NAG (Figure 2). This distinctive value for adriamycin‐induced nephrotoxicity is comparable with those reported by other research groups [2,4,41–43].…”

Section: Discussionsupporting

confidence: 91%

“…In the non‐enzymatic mechanism, adriamycin will form a complex with iron that is able to reduce oxygen to different active oxygen species [4,44]. The role of free‐radical formation, and the consequent oxidative stress, in the induction of adriamycin‐induced nephrotoxicity is now widely accepted, as indicated by different studies that support this notion [3,4,6,41,43–46].…”

Section: Discussionmentioning

confidence: 99%

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Ginkgo biloba leaf extract (EGb 761) diminishes adriamycin‐induced hyperlipidaemic nephrotoxicity in rats: association with nitric oxide production

Abd-Ellah

Mariee

2007

Biotech and App Biochem

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The aim of this experimental study was to investigate the effect of a standardized preparation of Ginkgo biloba extract (EGb 761) on the hyperlipidaemic nephrotoxicity and oxidative stress induced by a single intravenous injection (5 mg/kg) of adriamycin. EGb 761 was received daily thereafter by a gavage at the dose of 100 mg/kg for 35 consecutive days. EGb 761 administration significantly attenuated adriamycin-induced renal dysfunction, as assessed by measuring serum lipid profile, serum total protein, serum urea and Ccr (creatinine clearance). Furthermore, urinary excretions of protein and NAG (N-acetyl-beta-D-glucosaminidase; a marker of renal tubular injury) were significantly inhibited following EGb 761 administration. EGb 761 supplementation significantly prevented the generation of TBARS (thiobarbituric acid-reacting substances) with a marked improvement in terms of GSH content and activity of antioxidant enzymes in the kidney homogenate. Moreover, EGb 761 treatment significantly reduced both renal-tissue and urine total NO (nitric oxide) levels. The results suggest that the protective potential of EGb 761 in the prevention of adriamycin-induced hyperlipidaemic nephrotoxicity in rats was associated with the decrease in the oxidative stress and the total NO levels of renal tissues. Likewise, the present study demonstrates the ability of EGb 761 to reduce the hyperlipidaemia and proteinuria associated with this nephropathy, which might be beneficial to enhance the therapeutic index of adriamycin.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Ginkgo biloba leaf extract (EGb 761) diminishes adriamycin‐induced hyperlipidaemic nephrotoxicity in rats: association with nitric oxide production

Abd-Ellah

Mariee

2007

Biotech and App Biochem

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“…Moreover, unsuccessful detection of these peptides in all RCC samples could be linked to a cancer-specific decrease. The levels of GPxP expression were evaluated in several pathological states, and in progression of autosomal dominant polycystic kidney disease [36,37], and in chronic renal failure [38]. This protein is structurally, functionally, and antigenically distinct from three Activity levels were evaluated detecting production of oxidized glutathione by all selenium-dependent enzymes, in presence of NADPH, without antigenic distinction.…”

Section: Discussionmentioning

confidence: 99%

Modified expression of plasma glutathione peroxidase and manganese superoxide dismutase in human renal cell carcinoma

Sarto¹,

Frutiger

Cappellano³

et al. 1999

Electrophoresis

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Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) is a powerful tool to separate thousands of polypeptides and to highlight the modification of protein expression in malignant diseases. By applying 2-D PAGE to ten normal human kidney and ten homologous renal cell carcinoma (RCC) tissues, we found two peptides in all ten normal tissues but not in RCCs and, conversely, two peptides were detected in all RCCs but not in normal tissues. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and internal sequence analysis, the two first peptides were identified as two isoforms of plasma glutathione peroxidase (GPxP). The two other peptides isolated in all RCCs but not in normal tissues were identified by N-terminal sequence analysis as multimeric forms of manganese superoxide dismutase (Mn-SOD). No multimeric Mn-SODs and only two monomeric forms were detected in normal tissues. GPxP and Mn-SOD are metallo-enzymes encoded on chromosome 5q32 and on chromosome 6p25, respectively. Their regions are within the locus 5q21-->qter and 6q21-6q27 on which deletions and translocations are described in some cytogenetic studies of RCC transformation. Therefore, our results might suggest a correlation between the modified expression of GPxP and Mn-SOD in tumor tissues and chromosomal modifications, and that the two proteins may be putative markers for diagnosis of RCC.

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“…Therefore, redox-directed therapies that increase prooxidant levels, deplete low molecular weight thiol antioxidants, or inhibit antioxidant enzymes have offered avenues to selectively induce cytotoxicity in cancer cells[218]. MM patients show parameters of oxidative stress[141] and manipulation of cellular redox parameters to augment therapeutic responses have provided encouraging results in B-cell malignancies[219]. Our published results show that oxidative stress-inducing drug combinations result in selective cytotoxicity in MM cells…”

mentioning

confidence: 79%

“…Despite the increasing evidence that IL-6-induced pro-oxidant production could confer an adaptive response in normal tissues, the relationship between IL-6-mediated resistance to oxidative stress and myeloma cell resistance to therapy is unknown.In comparison with normal tissues, cancer cells thrive in a prooxidant environment and are tolerant to oxidative stress[297]. Indeed, MM patients show increased lipid peroxidation and lower levels of antioxidant enzymes in plasma and erythrocytes[141,219,298,299]. MnSOD [manganese SOD (superoxide dismutase)] plays a major role in maintaining cellular antioxidant capacity[300,301].…”

mentioning

confidence: 99%

Copper-zinc superoxide dismutase and glucose metabolism as redox targets for bortezomib resistance in multiple myeloma

Salem¹

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Kristen, who were always there to say "it works because it is science" or "I hear the jury's still out on science" just to make me laugh. I am truly blessed by each of you. To my niece who is the most welcomed of distractions and with just a picture can brighten my day. Words do no justice with how grateful I am to each Salem, thank you for your love and support without it, I would not have made it to the finish line. v ABSTRACT Multiple myeloma (MM) is a prevalent B-cell neoplasm that remains incurable with currently available chemotherapeutic drugs. Existing drug regimens result in initial disease remission but MM often relapses with an aggressive, drug resistant phenotype with uniform mortality. Bortezomib (BTZ, proteasome inhibitor) is a frontline anti-MM drug that is used for treatment of newly diagnosed and relapsed MM. However both intrinsic and acquired BTZ resistance is observed. Hence, gaining a mechanistic understanding of BTZresistance can provide novel targets to increase and restore BTZ cytotoxicity in MM. Studies show that BTZ-mediated proteasome inhibition generates oxidative stress therefore, BTZ resistance can be caused by an increase in cellular antioxidant capacity of MM cells. Antioxidants like superoxide dismutases (SODs), glutathione (GSH), and glutathione peroxidases (GPxs) can maintain cellular redox homeostasis and confer resistance to oxidative stress. Additionally, an increased glucose metabolism can assist in maintaining low reactive oxygen species (ROS) levels formed as by-products of endogenous or therapy induced oxidative stress. This led us to test the hypothesis that BTZ resistance in MM is linked to redox regulation via the antioxidant network and generation of reducing equivalents. Retrospective analysis of clinically annotated MM dataset shows a correlation between SOD1 gene expression, MM progression, and poor overall and event free survival. In a MM cell line model with intrinsic or acquired BTZ resistance, our results show a correlation between half maximal inhibitory concentration (IC 50) of BTZ and CuZnSOD activity. Upon inhibition of CuZnSOD vi activity with a clinically approved drug, disulfiram (DSF, Antabuse), BTZ cytotoxicity was increased. Furthermore, enforced overexpression of CuZnSOD conferred BTZ resistance in an otherwise BTZ sensitive MM cell line. MM cell lines with differential intrinsic BTZ cytotoxicity displayed a correlation between BTZ IC 50 and GSH levels as well as GPx-1 activity. Gene expression profiling data from patients showed that poor prognosis associates with increased glycolytic gene expression in MM. Also, MM cell lines with intrinsic resistance toward BTZ exhibited increased glucose uptake, increased mRNA expression and activity of glucose-6-phosphate dehydrogenase (G6PD) with increased cytotoxicity with glucose deprivation or 2-deoxyglucose (2-DG) treatment. In conclusion, our results provide a rationale for utilizing redox-based combination protocols of clinically approved drugs (i.e. DSF and 2-DG) with BTZ to improve MM therapy responses....

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The influence of cyclosporine on lipid peroxidation and superoxide dismutase in adriamycine nephropathy in rats

Cited by 3 publications

References 0 publications

Ginkgo biloba leaf extract (EGb 761) diminishes adriamycin‐induced hyperlipidaemic nephrotoxicity in rats: association with nitric oxide production

Ginkgo biloba leaf extract (EGb 761) diminishes adriamycin‐induced hyperlipidaemic nephrotoxicity in rats: association with nitric oxide production

Modified expression of plasma glutathione peroxidase and manganese superoxide dismutase in human renal cell carcinoma

Copper-zinc superoxide dismutase and glucose metabolism as redox targets for bortezomib resistance in multiple myeloma

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