Effects of carnosine on cyclophosphamide-induced hematopoietic suppression in mice.

Cyclophosphamide is one of the most widely used chemotherapeutic agents in treating cancers. Chemotherapy drug-induced oxidative stress produces side effects. The severity of myelosuppression increases with a high dose of cyclophosphamide. Chicken soup or chicken essence, a traditional Chinese aliment, is a popular health supplement for patients with cancers or other diseases in Asia. As a major functional component of chicken meat extract, carnosine (beta-alanyl-L-histidine), a dipeptide of the amino acids beta-alanine and histidine, has been shown to have strong antioxidant activities. In the present study, we investigated the effects of carnosine on hematopoietic suppression in mice treated with cyclophosphamide. As expected, we found that cyclophosphamide administration (with a single dose of 150 mg/kg) induced a rapid (within 24 hours) and severe hematopoietic suppression in mice. We further showed that carnosine administration (100 mg/kg/day or 200 mg/kg/day for continuous seven days) could substantially improve suppressed hematopoietic functions and accelerate the recovery of leukocyte counts, bone marrow spontaneous proliferation, colony stimulating activity (CSA) in serum, and production of endogenous cytokines such as interleukin-3 (IL-3) and stem cell factor (SCF). These results indicate that carnosine has the potential to promote the recovery from hematopoietic suppression induced by cyclophosphamide. Our data suggest that carnosine holds a potential in clinical application to minimize the side effects induced by chemotherapeutic agents such as cyclophosphamide and thus will substantially improve the overall anti-tumor effects of the standard chemotherapies.

[1]  L. Ng,et al.  Immunomodulatory activities of medicinal mushroom Grifola frondosa extract and its bioactive constituent. , 2013, The American journal of Chinese medicine.

[2]  Ki Yong Lee,et al.  Safety and Efficacy Evaluation of Carnosine, an Endogenous Neuroprotective Agent for Ischemic Stroke , 2013, Stroke.

[3]  C. Yang,et al.  Effect of Curculigo orchioides on reflux esophagitis by suppressing proinflammatory cytokines. , 2012, The American journal of Chinese medicine.

[4]  David J. Fleet,et al.  A preliminary, randomized, double-blind, placebo-controlled trial of l-carnosine to improve cognition in schizophrenia , 2012, Schizophrenia Research.

[5]  S. Aydoğan,et al.  Effect of carnosine on erythrocyte deformability in diabetic rats , 2012, Archives of physiology and biochemistry.

[6]  S. Hosseinimehr,et al.  Chemoprotective effects of carnosine against genotoxicity induced by cyclophosphamide in mice bone marrow cells , 2012, Cell biochemistry and function.

[7]  Euikyung Kim,et al.  Evaluation of the genotoxicity of extracts of Houttuynia cordata Thunb. , 2012, The American journal of Chinese medicine.

[8]  H. Moins-Teisserenc,et al.  Immunomodulatory effects of aqueous and organic fractions from Petiveria alliacea on human dendritic cells. , 2012, The American journal of Chinese medicine.

[9]  Chong-Zhi Wang,et al.  Herbal medicines as adjuvants for cancer therapeutics. , 2012, The American journal of Chinese medicine.

[10]  I. Jang,et al.  Mountain ginseng extract exhibits anti-lung cancer activity by inhibiting the nuclear translocation of NF-κB. , 2012, The American journal of Chinese medicine.

[11]  R. He,et al.  Anti-Stress Effects of Carnosine on Restraint-Evoked Immunocompromise in Mice through Spleen Lymphocyte Number Maintenance , 2012, PloS one.

[12]  F. Gaunitz,et al.  Carnosine and cancer: a perspective , 2012, Amino Acids.

[13]  K. Nagai,et al.  Effects of l-carnosine on splenic sympathetic nerve activity and tumor proliferation , 2012, Neuroscience Letters.

[14]  S. Barni,et al.  Optimal use of recombinant granulocyte colony-stimulating factor with chemotherapy for solid tumors , 2011, Expert review of anticancer therapy.

[15]  J. Braybrooke,et al.  Management of uncommon chemotherapy-induced emergencies. , 2011, The Lancet. Oncology.

[16]  J. Meixensberger,et al.  Identification of Factors Involved in the Anti-Tumor Activity of Carnosine on Glioblastomas Using a Proteomics Approach , 2011, Cancer investigation.

[17]  M. Nakajima,et al.  Antioxidant Combination Inhibits Reactive Oxygen Species Mediated Damage , 2008, Bioscience, biotechnology, and biochemistry.

[18]  K. Conklin.  Chemotherapy-Associated Oxidative Stress: Impact on Chemotherapeutic Effectiveness , 2004, Integrative cancer therapies.

[19]  A. Ichikawa,et al.  Interleukin 3 promotes histamine synthesis in hematopoietic progenitors by increasing histidine decarboxylase mRNA expression. , 1993, Biochemical and Biophysical Research Communications - BBRC.

[20]  S. Biffo,et al.  Cellular localization of carnosine-like and anserine-like immunoreactivities in rodent and avian central nervous system , 1990, Neuroscience.

[21]  E. N. Goncharenko,et al.  [The radiation modifying properties of carnosine]. , 1990, Radiobiologiia.

[22]  O. Aruoma,et al.  Carnosine, homocarnosine and anserine: could they act as antioxidants in vivo? , 1989, The Biochemical journal.

[23]  F. Ruscetti,et al.  Release of colony-stimulating activity from thymus-derived lymphocytes. , 1975, The Journal of clinical investigation.

[24]  Meng Xu,et al.  Reversal effect of Stephania tetrandra-containing Chinese herb formula SENL on multidrug resistance in lung cancer cell line SW1573/2R120. , 2010, The American journal of Chinese medicine.

[25]  A. Hipkiss.  Carnosine and its possible roles in nutrition and health. , 2009, Advances in food and nutrition research.

[26]  Y. Guney,et al.  Carnosine may reduce lung injury caused by radiation therapy. , 2006, Medical hypotheses.

[27]  W. Waud,et al.  Antitumor activity of halogen analogs of phosphoramide, isophosphoramide, and triphosphoramide mustards, the cytotoxic metabolites of cyclophosphamide, ifosfamide, and trofosfamide , 2004, Cancer Chemotherapy and Pharmacology.