Pharmacokinetics, tissue distribution and excretion of manganese (III) meso-tetra [3-(2-(2-methoxy)-ethoxy) ethoxy] phenyl porphyrin chloride, a novel superoxide dismutase mimic, in Wistar rats

Bao-qiu, LI; Fang, Shi-hong; Dong, Xin; Li, Na; Gao, Ji-you; Yang, Guiqin; Gong, Xianchang; Wang, Shujuan; Wang, Fengshan

doi:10.1007/s13318-013-0118-0

Cited by 5 publications

(12 citation statements)

References 33 publications

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“…The presence of these oxygens,t ogether with the high lipophilicity confer excellent chemical and physical properties to Mn 3 + meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin, MnTnBuOE-2-PyP 5 + (MnBuOE, BMX-001). [118] Initial pharmacological studies demonstrated that HSJ-0017 improved the therapeutic effects and reduced the toxicities arising from radiation and cyclophosphamide in B16/ F1 murinem elanoma-bearing C57BL/6 models. In fact, MnBuOE reduced radiotherapy-mediated mucositis, xerostomia and fibrosis, thus, protecting normal tissue.…”

Section: Manganese Porphyrinsmentioning

confidence: 99%

“…In their preliminarys tudies, they found that HSJ-0017 is distributed quickly to blood-rich organs and accumulates in mitochondria following intravenous injection. [118] Initial pharmacological studies demonstrated that HSJ-0017 improved the therapeutic effects and reduced the toxicities arising from radiation and cyclophosphamide in B16/ F1 murinem elanoma-bearing C57BL/6 models. Their latest studies show that HSJ-0017 is a powerful SOD/CAT mimetic, which enhances the antitumour effects of chemotherapy and radiotherapy,w hilst reducing their negative side effects.…”

Section: Manganese Porphyrinsmentioning

confidence: 99%

“…developed another lipophilic Mn porphyrin‐based mimic, manganese(III) 5, 10, 15, 20‐tetrakis [3‐(2‐(2‐methoxy)‐ethoxy) ethoxy] phenylporphyrin chloride (molecular formula: C 64 H 68 ClMnN 4 O 12 ), designated HSJ‐0017, used to treat diseases related to free radicals. In their preliminary studies, they found that HSJ‐0017 is distributed quickly to blood‐rich organs and accumulates in mitochondria following intravenous injection . Initial pharmacological studies demonstrated that HSJ‐0017 improved the therapeutic effects and reduced the toxicities arising from radiation and cyclophosphamide in B16/ F1 murine melanoma‐bearing C57BL/6 models.…”

Section: Sod‐mimetics and Their Possible Clinical Usesmentioning

confidence: 99%

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Potential Therapeutic Applications of MnSODs and SOD‐Mimetics

Bonetta

2017

Chemistry A European J

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Natural as well as synthetic antioxidants are constantly being investigated for their efficiency in combatting the effects of oxidative stress, which appears to be the responsible cause of several diseases, including cancer, central nervous system disorders, ischaemia-reperfusion disorders, cardiovascular conditions, and diabetes. Superoxide dismutases (SODs) constitute the ubiquitous antioxidant defences against oxidative stress that underlies numerous pathological conditions. Therefore, the development of therapeutics aimed at either delivering MnSOD more effectively to target tissues in the body in the form of MnSOD gene therapy, or the synthesis of molecules that mimic the activity of superoxide dismutase is constantly being explored. Classes that have been developed as SOD mimetics include the Mn-metalloporphyrins, Mn-cyclic polyamines, Mn-salen complexes, MnPLED derivatives as well as the nitroxides. Thus far, SOD mimetics have shown remarkable efficacy in several animal models suffering from oxidative stress injuries. A promising approach for the future of SOD and SOD mimic therapeutics appears to involve combination treatment of the antioxidants with radiotherapy or chemotherapy.

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Section: Manganese Porphyrinsmentioning

confidence: 99%

Section: Manganese Porphyrinsmentioning

confidence: 99%

Section: Sod‐mimetics and Their Possible Clinical Usesmentioning

confidence: 99%

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Potential Therapeutic Applications of MnSODs and SOD‐Mimetics

Bonetta

2017

Chemistry A European J

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“…Several studies showed that the plasma concentration levels of porphyrin-like photosensitizers rapidly decreased after intravenous injection, exhibiting a bi-exponential decline with a rapid distribution phase followed by a moderately rapid elimination phase. 31,32 In addition, the rapid elimination of DVDMS contributed to a short light-avoidance period. C max and AUC 0−t after the first administration increased proportionally with the dose in a linear fashion, and no saturation was observed.…”

Section: Discussionmentioning

confidence: 99%

A safety study of a novel photosensitizer, sinoporphyrin sodium, for photodynamic therapy in Beagle dogs

Li²,

Wang³

et al. 2015

Photochem Photobiol Sci

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Sinoporphyrin sodium (DVDMS) is a novel hematoporphyrin-like photosensitizer developed for photodynamic therapy (PDT), an effective therapeutic modality for tumor treatment; however, the safety of photosensitizer-based PDT is always of great concern. The purpose of the current study was to investigate the potential repeated-dose toxicity and describe the toxicokinetic process of DVDMS-based PDT in Beagle dogs. The dogs were randomly allocated to six groups, and then were administrated a DVDMS preparation intravenously at dose levels of 0, 1, 3, 9, 1 and 9 mg per kg body weight, respectively; then, the latter two groups were illuminated 24 h later with a 630 nm laser for 10 min, once every seven days for 5 weeks. During the study period, clinical signs, mortality, body weight, food consumption, body temperature, ophthalmoscopy, hematology, serum biochemistry, urinalysis, electrocardiograms, toxicokinetics, organ weights, gross anatomy and histopathology were examined. After the administration, no deaths were observed; however, the dogs that received PDT showed skin swelling and ulceration, indicating that DVDMS-PDT induced a phototoxic effect. DVDMS led to an increase in blood coagulation in dogs in the 9 mg kg(-1) group and in the two PDT groups on Day 35, whereas it induced a decrease in dogs in the 3 mg kg(-1) group and in the two PDT groups on Day 49. The toxicokinetic study showed that the systematic exposure of DVDMS in dogs occurred in a dose-dependent manner, and DVDMS did not accumulate in blood plasma. The DVDMS-based PDT group showed no obvious treatment-related pathological changes; however, slight or mild brown-and-yellow pigmentation of DVDMS (or its metabolite) was observed to deposit in the liver, spleen, local lymph nodes and marrow of dogs in the mid- and high-dose groups, as well as the high-dose PDT group. In females, the absolute and relative spleen weights increased in dogs in the 9 mg kg(-1) DVDMS groups with and without PDT during the treatment and recovery period, respectively. The target organs are presumed to be the liver and immune organs (spleen, bone marrow and lymph nodes), while all of the responses were slight. Based on the results above, the no-observed-adverse-effect level (NOAEL) was considered to be 1 mg kg(-1), and DVDMS-PDT appeared to be a safe and promising anti-tumor therapy in the clinic.

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“…Our previous studies have demonstrated that HSJ-0017 can be rapidly distributed to blood-rich organs and accumulated in mitochondria after intravenous injection. 17 Preliminary pharmacological studies have revealed that HSJ-0017 can enhance the therapeutic effects and reduce the toxicities of radiation and cyclophosphamide in B16/ F1 murine melanoma-bearing C57BL/6 mice. 18 Despite its good pharmacokinetic properties and potent, synergistic antitumor effects, the therapeutic potential of HSJ-0017 has not been extensively studied.…”

Section: Introductionmentioning

confidence: 99%

In vitro enzyme-mimic activity and in vivo therapeutic potential of HSJ-0017, a novel Mn porphyrin-based antioxidant enzyme mimic

Bao-qiu

Dong²,

Li³

et al. 2014

Exp Biol Med (Maywood)

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Manganese (III) 5, 10, 15, 20-tetrakis [3-(2-(2-methoxy)-ethoxy) ethoxy] phenyl porphyrin chloride, designated HSJ-0017, is a novel antioxidant enzyme mimic. The aim of the present study was to investigate the enzyme-mimic activity and the therapeutic potential of HSJ-0017 in free radical-related diseases. Superoxide dismutase (SOD) mimic activity was measured by the nitroblue tetrazolium chloride monohydrate reduction assay. Catalase (CAT) mimic activity was measured based on the decomposition of hydrogen peroxide. The antitumor, radioprotective and chemoprotective effects of HSJ-0017 were evaluated in H22 or S180 tumor-bearing Kunming mice. The anti-inflammatory and hepatoprotective effects were, respectively, evaluated in histamine-induced edema model and CCl4-induced hepatic damage model in Wistar rats. HSJ-0017 over a concentration range of 0.001-10 µmol/L significantly inhibited the generation of superoxide anion. Significant hydrogen peroxide scavenging activity was observed when the concentration of HSJ-0017 was higher than 0.01 µmol/L. HSJ-0017 at a dose of 3.0 mg/kg exhibited significant antitumor effect on S180 tumor xenografts, whereas no significant antitumor effect was observed in H22 tumor xenografts. HSJ-0017 at a dose of 3.0 mg/kg enhanced the antitumor effects of radiotherapy and chemotherapy, and reduced their toxicity. However, HSJ-0017 counteracted the antitumor effects of radiotherapy when administered simultaneously with radiotherapy. HSJ-0017 showed significant anti-inflammatory and hepatoprotective effects. Our results demonstrate that HSJ-0017 exhibits antioxidant, antitumor, anti-inflammatory, radioprotective, chemoprotective, and hepatoprotective effects. It is a potent dual SOD/CAT mimic.

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Pharmacokinetics, tissue distribution and excretion of manganese (III) meso-tetra [3-(2-(2-methoxy)-ethoxy) ethoxy] phenyl porphyrin chloride, a novel superoxide dismutase mimic, in Wistar rats

Cited by 5 publications

References 33 publications

Potential Therapeutic Applications of MnSODs and SOD‐Mimetics

Potential Therapeutic Applications of MnSODs and SOD‐Mimetics

A safety study of a novel photosensitizer, sinoporphyrin sodium, for photodynamic therapy in Beagle dogs

In vitro enzyme-mimic activity and in vivo therapeutic potential of HSJ-0017, a novel Mn porphyrin-based antioxidant enzyme mimic

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