Mangafodipir prevents liver injury induced by acetaminophen in the mouse

Bedda, Sassia; Laurent, Alexis; Conti, Filomena; Chéreau, Chistiane; Tran, A.; Nhieu, Jeanne Tran-Van; Jaffray, Patrick; Soubrane, Olivier; Goulvestre, Claire; Calmus, Yvon; Weill, Bernard; Batteux, Frédéric

doi:10.1016/s0168-8278(03)00325-8

Cited by 58 publications

(59 citation statements)

References 29 publications

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“…Since AOPP levels were reduced in mice after 4 weeks of treatment with mangafodipir, we undertook to determine which step of the oxidative cascade was targeted by the molecule. Like mangafodipir, MnTBAP is a chelate of manganese with SOD-like activity, but unlike mangafodipir, it is devoid of vitamin B6 activity (16). Unlike vitamin B6, we found that MnTBAP prevented neuromuscular hyperexcitability, findings that are in accordance with those of Ang et al following administration of vitamin B complex (28).…”

Section: Discussionsupporting

confidence: 91%

“…Vitamin B6 is known for its ability to maintain normal neurological functions and for its neuroprotective activity (15). In addition, given that mangafodipir is endowed with SOD-, catalase-, and glutathione reductase-like (GR-like) properties, it can target multiple steps of the ROS cascade by detoxifying superoxide anions and hydrogen peroxide and by restoring GSH (16,17). Moreover, this molecule is known to cross the cell membrane, and we have already shown its ability to improve the therapeutic index of oxaliplatin (18).…”

Section: Introductionmentioning

confidence: 99%

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Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir

Coriat¹,

Alexandre²,

Nicco³

et al. 2013

J. Clin. Invest.

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Background. The majority of patients receiving the platinum-based chemotherapy drug oxaliplatin develop peripheral neurotoxicity. Because this neurotoxicity involves ROS production, we investigated the efficacy of mangafodipir, a molecule that has antioxidant properties and is approved for use as an MRI contrast enhancer.Methods. The effects of mangafodipir were examined in mice following treatment with oxaliplatin. Neurotoxicity, axon myelination, and advanced oxidized protein products (AOPPs) were monitored. In addition, we enrolled 23 cancer patients with grade ≥2 oxaliplatin-induced neuropathy in a phase II study, with 22 patients receiving i.v. mangafodipir following oxaliplatin. Neuropathic effects were monitored for up to 8 cycles of oxaliplatin and mangafodipir. Funding.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir

Coriat¹,

Alexandre²,

Nicco³

et al. 2013

J. Clin. Invest.

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“…Our results suggest that the BE is mostly related to peroxynitrite because it is inhibited by a NO synthase inhibitor, L-NAME and mangafodipir, a superoxide dismutase mimic known to decrease superoxide accumulation. 20 Accordingly, catalase, the H 2 O 2 scavenger, had no significant influence on the vinorelbine BE. …”

Section: Discussionmentioning

confidence: 95%

Bystander effect of vinorelbine alters antitumor immune response

Thomas-Schoemann

Lemare

Mongaret

et al. 2011

Intl Journal of Cancer

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The bystander effect (BE) is the ability of malignant cells affected by an anticancer agent to induce damage in neighboring cancer cells. In this study, we showed that it could also affect immune cells surrounding the tumor and interfere with the antitumor immune response. We observed that the exposure of human lung cancer cells A549 to vinorelbine induced a BE on neighboring human peripheral blood mononuclear cells (PBMCs) in vitro and on mice splenocytes in vivo. In vitro, the number of PBMCs killed because of their coculture with vinorelbine-pretreated A549 cells was 33% higher than those killed by A549 control cells (p 5 0.003). In addition, we showed that when vinorelbine-pretreated A549 cells were injected into immunocompetent mice, splenocyte proliferation ex vivo toward tumor cells decreased by 27% compared with that seen in mice injected with untreated A549 cells (p 5 0.03). Finally, in vivo experiment in A549 tumor bearing nude mice showed that adoptive transfer of A549 immune splenocytes was not able to delay tumor growth when vinorelbine-pretreated A549 cells were used for immunization. Inhibition of the BE by the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester, and the superoxide dismutase mimic, mangafodipir, suggested that it was mediated by oxidative and nitrosative stress. In conclusion, exposure of cancer cells to vinorelbine alters the antitumor immune response through a BE mediated by cellular oxidative and nitrosative stress. Our results offer new prospects for using oxidative stress modulators to restore the antitumor immune response in patients treated with anticancer agents.The bystander effect (BE) initially described in the gene therapy field has recently gained popularity in oncology.

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“…Caspase-3 activity was measured in liver cytosolic fractions as previously described. 33 Results are expressed as pmol ⅐ min Ϫ1 mg Ϫ1 protein.…”

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confidence: 99%

Reg2 inactivation increases sensitivity to Fas hepatotoxicity and delays liver regeneration post-hepatectomy in mice

et al. 2006

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Reg2/RegIII␤ is the murine homologue of the human secreted HIP/PAP C-type lectin. HIP/PAP transgenic mice were protected against acetaminophen-induced acute liver failure and were stimulated to regenerate post-hepatectomy. To assess the role of Reg2, we used Reg2؊/؊ mice in a model of fulminant hepatitis induced by Fas and in the post-hepatectomy regeneration. Within 4 hours of J0-2 treatment (0.5 g/g), only 50% of the Reg2؊/؊ mice were alive but with an increased sensitivity to Fas-induced oxidative stress and a decreased level of Bcl-xL. In contrast, HIP/PAP transgenic mice were resistant to Fas, with HIP/PAP serving as a sulfhydryl buffer to slow down decreases in glutathione and Bcl-xL. In Reg2؊/؊ mice, liver regeneration was markedly impaired, with 29% mortality and delay of the S-phase and the activation of ERK1/2 and AKT. Activation of STAT3 began on time at 3 hours but persisted strongly up to 72 hours despite significant accumulation of SOCS3. Thus, Reg2 deficiency induced exaggerated IL-6/STAT-3 activation and mito-inhibition. Because the Reg2 gene was activated between 6 and 24 hours after hepatectomy in wild-type mice, Reg2 could mediate the TNF-␣/IL-6 priming signaling by exerting a negative feedback on STAT3/IL-6 activation to allow the hepatocytes to progress through the cell cycle. In conclusion, Reg2 deficiency enhanced liver sensitivity to Fas-induced oxidative stress and delayed liver regeneration with persistent TNF-␣/IL6/STAT3 signaling. In contrast, overexpression of human HIP/PAP promoted liver resistance to Fas and accelerated liver regeneration with early activation/deactivation of STAT3. Reg2/HIP/PAP is therefore a critical mitogenic and antiapoptotic factor for the liver. (HEPATOLOGY 2006;44:1452-1464 F as/FasL (APO-1, CD95) interaction is involved in many pathological situations such as graft-versushost disease, liver transplant and major surgical resection, hepatitis B and C, acute alcoholic hepatitis, drug overdose, and some biliary diseases. Fas activation-induced acute liver failure is characterized by massive hepatic necrosis/apoptosis. Survival of patients depends on the speed with which quiescent liver cells re-enter the cell

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Mangafodipir prevents liver injury induced by acetaminophen in the mouse

Cited by 58 publications

References 29 publications

Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir

Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir

Bystander effect of vinorelbine alters antitumor immune response

Reg2 inactivation increases sensitivity to Fas hepatotoxicity and delays liver regeneration post-hepatectomy in mice

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