Repeated dose 28-day oral toxicity study of DEAE-Dextran in mice: An advancement in safety chemotherapeutics |
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| Institution: | 1. Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat 382 481, India;2. Zydus Research Centre, Sarkhej-Bavla, Changodhar, Gujarat 382210, India;3. Sukoon Pathology Laboratory, Ahmedabad, Gujarat 380052, India;1. Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ, 07677, USA;2. Member RIFM Expert Panel, Columbia University Medical Center, Department of Dermatology, 161 Fort Washington Ave., New York, NY, 10032, USA;3. Member RIFM Expert Panel, Malmo University Hospital, Department of Occupational & Environmental Dermatology, Sodra Forstadsgatan 101, Entrance 47, Malmo, SE-20502, Sweden;4. Member RIFM Expert Panel, School of Natural Resources & Environment, University of Michigan, Dana Building G110, 440 Church St., Ann Arbor, MI, 58109, USA;5. Member RIFM Expert Panel, Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Strasse 1, 30625, Hannover, Germany;6. Member RIFM Expert Panel, University of Sao Paulo, School of Veterinary Medicine and Animal Science, Department of Pathology, Av. Prof. dr. Orlando Marques de Paiva, 87, Sao Paulo CEP, 05508-900, Brazil;7. Member RIFM Expert Panel, University of Wuerzburg, Department of Toxicology, Versbacher Str. 9, 97078 Würzburg, Germany;8. Member RIFM Expert Panel, Oregon Health Science University, 3181 SW Sam Jackson Park Rd., Portland, OR, 97239, USA;9. Member RIFM Expert Panel, Vanderbilt University School of Medicine, Department of Biochemistry, Center in Molecular Toxicology, 638 Robinson Research Building, 2200 Pierce Avenue, Nashville, TN, 37232-0146, USA;10. Member of RIFM Expert Panel, University of Pennsylvania, Perelman School of Medicine, Center of Excellence in Environmental Toxicology, 1316 Biomedical Research Building (BRB) II/III, 421 Curie Boulevard, Philadelphia, PA, 19104-3083, USA;11. Member RIFM Expert Panel, The University of Tennessee, College of Veterinary Medicine, Department of Comparative Medicine, 2407 River Dr., Knoxville, TN, 37996- 4500, USA;12. Member RIFM Expert Panel, Department of Pharmacology, University of Arizona, College of Medicine, 1501 North Campbell Avenue, P.O. Box 245050, Tucson, AZ, 85724-5050, USA;13. Member RIFM Expert Panel, The Journal of Dermatological Science (JDS), Editor-in-Chief, Professor and Chairman, Department of Dermatology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan;1. Research Institute for Fragrance Materials, Inc, 50 Tice Boulevard, Woodcliff Lake, NJ, 07677, USA;2. Columbia University Medical Center, Department of Dermatology, 161 Fort Washington Ave, New York, NY, 10032, USA;3. Malmo University Hospital, Department of Occupational & Environmental Dermatology, Sodra Forstadsgatan 101, Entrance 47, Malmo, SE-20502, Sweden;4. School of Natural Resources & Environment, University of Michigan, Dana Building G110, 440 Church St, Ann Arbor, MI, 58109, USA;5. Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Strasse 1, 30625, Hannover, Germany;6. University of Sao Paulo, School of Veterinary Medicine and Animal Science, Department of Pathology, Av. Prof. dr. Orlando Marques de Paiva, 87, Sao Paulo, CEP 05508-900, Brazil;7. University of Wuerzburg, Department of Toxicology, Versbacher Str. 9, 97078, Würzburg, Germany;8. Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA;9. Vanderbilt University School of Medicine, Department of Biochemistry, Center in Molecular Toxicology, 638 Robinson Research Building, 2200 Pierce Avenue, Nashville, TN, 37232-0146, USA;10. University of Pennsylvania, Perelman School of Medicine, Center of Excellence in Environmental Toxicology, 1316 Biomedical Research Building (BRB) II/III, 421 Curie Boulevard, Philadelphia, PA, 19104-3083, USA;11. The University of Tennessee, College of Veterinary Medicine, Department of Comparative Medicine, 2407 River Dr, Knoxville, TN, 37996- 4500, USA;12. Department of Pharmacology, University of Arizona, College of Medicine, 1501 North Campbell Avenue, P.O. Box 245050, Tucson, AZ, 85724-5050, USA;13. The Journal of Dermatological Science (JDS), Editor-in-Chief, Professor and Chairman, Department of Dermatology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan;1. DSM Nutritional Products, 6480 Dobbin Rd., Columbia, MD 21045, USA;2. DSM Nutritional Products, Wurmisweg 576, 4303 Kaiseraugst, Switzerland;3. Charles River Laboratories Preclinical Services, Spencerville, OH 45887, USA;1. Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, UT, USA;2. Department of Research and Pathology, Office of Comparative Medicine, University of Utah, Salt Lake City, UT, USA;3. Department of Radiology, Clinical Neurosciences Center, University of Utah, Salt Lake City, UT, USA;4. ARUP and Department of Veterinary Pathology, University of Utah, Salt Lake City, UT, USA;1. Bioneedle Group, Landgraaf, The Netherlands;2. Den Dolder, The Netherlands;3. Center for Dermatopathology, Freiburg, Germany;4. Dermatopharmacological Center, Freiburg, Germany |
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| Abstract: | Cancer has emerged as a global threat with challenges for safe chemotherapeutics. Most of the currently available anti-cancer drugs exhibit significant toxicity. Amongst novel agents, interferons have exhibited anti-proliferative and cytoprotective roles. However, due to stability drawbacks of interferons, we have identified an interferon inducer DEAE-Dextran, which resolves the stability issues. Based on the previous history of toxicity pertaining to the current chemotherapeutic agents, it is equally essential to determine the safety of DEAE-Dextran. In the present study, repeated dose 28 day oral toxicity of DEAE-Dextran has been evaluated in accordance to OECD-407. We found absence of any CNS behavioral changes related to self-mutilation, walking backwards, aggressiveness on handling or tonic-clonic seizures during the 28 day study. Neither the motor activity nor grip strength was altered during the treatment duration with DEAE-Dextran implying absence of any effect on the skeletal muscles. Interestingly, we also found that treatment with DEAE-Dextran did not present any significant cardiac, hepatic, renal, gastrointestinal, lymphatic or reproductive system toxicity or alteration in the body's normal physiology based upon the various organ function tests. Henceforth, it may be concluded that DEAE-Dextran is a safe anti-cancer agent devoid of any sub-acute toxicity. |
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| Keywords: | Oral toxicity DEAE-Dextran OECD 407 Gross necropsy Gross histopathology |
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