Effect of cisplatin and cobalt chloride on antioxidant enzymes in the livers of Lewis lung carcinoma-bearing mice: protective role of heme oxygenase

Christova, Tania; Gorneva, G.; Taxirov, Svetoslav; Duridanova, Dessislava; Setchenska, Milka S.

doi:10.1016/s0378-4274(02)00416-2

Cited by 37 publications

(26 citation statements)

References 36 publications

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“…The maximum tolerated doses of cisplatin in rodents have been reported to range from 6 to 12 mg/kg of body weight, depend- ing on the mouse strain (7,14,30,38). Ten percent lethal dose values of 8 mg/kg (13) to 15.5 mg/kg (37) have been reported for rodents.…”

Section: Resultsmentioning

confidence: 99%

Cisplatin Inhibition of Anthrax Lethal Toxin

Moayeri

Wiggins

Lindeman

et al. 2006

Antimicrob Agents Chemother

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Bacillus anthracis lethal toxin (LT) produces symptoms of anthrax in mice and induces rapid lysis of macrophages derived from certain inbred strains. LT is comprised of a receptor binding component, protective antigen (PA), which delivers the enzymatic component, lethal factor (LF), into cells. We found that mouse macrophages were protected from toxin by the antitumor drug cis-diammineplatinum (II) dichloride (cisplatin). Cisplatin was shown to inhibit LT-mediated cleavage of cellular mitogen-activated protein kinases (MEKs) without inhibiting LF's in vitro proteolytic activity. Cisplatin-treated PA lost 100% of its ability to function in toxicity assays when paired with untreated LF, despite maintaining the ability to bind to cells. Cisplatin-treated PA was unable to form heptameric oligomers required for LF binding and translocation. The drug was shown to modify PA in a reversible noncovalent manner. Not surprisingly, cisplatin also blocked the actions of anthrax edema toxin and of LF-Pseudomonas aeruginosa exotoxin A fusion peptide (FP59), both of which require PA for translocation. Treatment of BALB/cJ mice or Fischer F344 rats with cisplatin at biologically relevant concentrations completely protected the animals from a coadministered lethal dose of LT. However, treatment with cisplatin 2 hours before or after animals received a lethal bolus of toxin did not protect them.

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Section: Resultsmentioning

confidence: 99%

Cisplatin Inhibition of Anthrax Lethal Toxin

Moayeri

Wiggins

Lindeman

et al. 2006

Antimicrob Agents Chemother

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“…Cisplatin treatment at both the dosages brought about increase in LDH level which is related to the studies of Sudhakar et al [56] where cisplatin treatment significantly increased the enzyme activities of SGOT, SGPT and LDH levels. It has been established that lipid peroxidation might participate in the hepatotoxicity in cisplatin-treated animals despite activation of antioxidant enzymes [57]. It has been suggested that antioxidant enzymes represent the protective response against cisplatin toxicity in the livers of tumor-bearing animals [53].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Nephroprotective and Immunomodulatory Activities of Antioxidants in Combination with Cisplatin against Murine Visceral Leishmaniasis

2012

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BackgroundMost available drugs against visceral leishmaniasis are toxic, and growing limitations in available chemotherapeutic strategies due to emerging resistant strains and lack of an effective vaccine against visceral leishmaniasis deepens the crisis. Antineoplastic drugs like miltefosine have in the past been effective against the parasitic infections. An antineoplastic drug, cisplatin (cis-diamminedichloroplatinum II; CDDP), is recognized as a DNA-damaging drug which also induces alteration of cell-cycle in both promastigotes and amastigotes leading to cell death. First in vivo reports from our laboratory revealed the leishmanicidal potential of cisplatin. However, high doses of cisplatin produce impairment of kidney, which can be reduced by the administration of antioxidants.Methodology/Principal FindingsThe present study was designed to evaluate the antileishmanial effect of cisplatin at higher doses (5 mg and 2.5 mg/kg body weight) and its combination with different antioxidants (vitamin C, vitamin E and silibinin) so as to eliminate the parasite completely and reduce the toxicity. In addition, various immunological, hematological and biochemical changes induced by it in uninfected and Leishmania donovani infected BALB/c mice were investigated.Conclusion/SignificanceA significant reduction in parasite load, higher IgG2a and lower IgG1 levels, enhanced DTH responses, and greater concentration of Th1 cytokines (IFN-γ, IL-2) with a concomitant down regulation of IL-10 and IL-4 pointed towards the generation of the protective Th1 type of immune response. A combination of cisplatin with antioxidants resulted in successful reduction of nephrotoxicity by normalizing the enzymatic levels of various liver and kidney function tests. Reduction in parasite load, increase in Th1 type of immune responses, and normalization of various biochemical parameters occurred in animals treated with cisplatin in combination with various antioxidants as compared to those treated with the drug only. The above results are promising as antioxidants reduced the potential toxicity of high doses of cisplatin, making the combination a potential anti-leishmanial therapy, especially in resistant cases.

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“…24 -30 Importantly, its expression in tumors can be potently induced in response to radio-, chemo-, or photodynamic therapies. 15,31,32 Nevertheless, the knowledge about the influence of HO-1 induction on progression of tumors is limited. Specifically, there are no data concerning the role of HO-1 in melanoma, the type of tumor relatively resistant to chemotherapeutic treatment.…”

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confidence: 99%

“…82 Importantly, treatment of cancer cells with chemotherapeutics such as gemcitabine or cis-platin as well as their exposure to radiation or photodynamic therapy can further increase HO-1 expression. 15,31,32 This up-regulation in response to therapeutic procedures may have important consequences. For example, in chronic myeloid leukemia-derived cell line K562, induction of HO-1 was found to counteract Gleevec (STI571)-induced apoptosis.…”

mentioning

confidence: 99%

Overexpression of Heme Oxygenase-1 in Murine Melanoma

Waś

Cichoń²,

Smolarczyk³

et al. 2006

The American Journal of Pathology

174

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Heme oxygenases (HOs) catalyze the oxidation of heme to the biologically active products carbon monoxide (CO), biliverdin, and ferrous iron. Two distinct variants of HOs have been described in humans and rodents, each encoded by a different gene: HO-2, which is constitutively expressed, and HO-1, which is potently induced in many cell types by heme, inflammatory cytokines, and oxidative stress-related factors.

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Effect of cisplatin and cobalt chloride on antioxidant enzymes in the livers of Lewis lung carcinoma-bearing mice: protective role of heme oxygenase

Cited by 37 publications

References 36 publications

Cisplatin Inhibition of Anthrax Lethal Toxin

Cisplatin Inhibition of Anthrax Lethal Toxin

Evaluation of Nephroprotective and Immunomodulatory Activities of Antioxidants in Combination with Cisplatin against Murine Visceral Leishmaniasis

Overexpression of Heme Oxygenase-1 in Murine Melanoma

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