Beijing Union Genius Pharmaceutical Technology Development Co.

Beijing, China

Beijing Union Genius Pharmaceutical Technology Development Co.

Beijing, China
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Lin N.,Peking Union Medical College | Liu T.,Peking Union Medical College | Lin L.,Peking Union Medical College | Lin S.,Peking Union Medical College | And 9 more authors.
Regulatory Toxicology and Pharmacology | Year: 2016

The standard of 5-Hydroxymethylfurfural (5-HMF) existed in dextrose injection as an inevitable by-product during high-temperature setrilization has been included in pharmacopoeias considering its hazardous effects on human health. We found that the concentrations of 5-HMF in some traditional Chinese medicine injections (TCMIs) far exceeded its limit in dextrose injection. Besides, we detected 5, 5'-Oxydimethylenebis (2-furfural) (OMBF) in those TCMIs containing high concentrations of 5-HMF. We investigated the in vivo immunomodulatory effects of 5-HMF and OMBF at three dose levels using the reporter antigen popliteal lymph node assay (RA-PLNA), which allows the straightforward examination and mechanistic study of immunotoxicity of low molecular weight compounds. We found that 5-HMF increased the production of IgG2a and IFN-γ when co-injected with TNP-OVA, indicating its capability of providing a co-stimulatory signal to evoke a typical type-1 immune response. Compared with the 5-HMF, OMBF elevated the production of IgG1, IgG2, IL-4 and IFN-γ in response to both reporter antigens, suggesting that OMBF can act as a neo-antigen or neo-epitope to elicit a mixed type-1 and type-2 immune response. It indicates that both 5-HMF and OMBF have immunosensitizing potential with different mechanisms, and exposure to 5-HMF and OMBF may represent a safety concern for humans. © 2016 Elsevier Inc.


Lin N.,Peking Union Medical College | Li C.,Beijing Union Genius Pharmaceutical Technology Development Co. | Wang Z.,Beijing Union Genius Pharmaceutical Technology Development Co. | Zhang J.,Beijing Union Genius Pharmaceutical Technology Development Co. | And 8 more authors.
Photochemical and Photobiological Sciences | Year: 2015

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. © The Royal Society of Chemistry and Owner Societies 2015.

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