Repeated Intraperitoneal Administration of Low-Concentration Methylcellulose Leads to Systemic Histologic Lesions Without Loss of Preclinical Phenotype

The Journal of Pharmacology and Experimental Therapeutics
Stacey MeekerMelissa Barker-Haliski

Abstract

Methylcellulose (MC; 0.5% concentration) is commonly used when evaluating investigational agents for efficacy in preclinical models of disease. When administered by the oral (PO) route, MC is considered a Food and Drug Administration "generally recognized as safe" compound. Yet, there is limited data pertaining to the tolerability and impact on model fidelity of repeated intraperitoneal administration of 0.5% MC. Chronic administration of high-concentration MC (2%-2.5%) has been used to induce anemia, splenomegaly, and lesions in multiple organ systems in several preclinical species. Histopathological findings from a diagnostic pathologic analysis of a single mouse from our laboratory with experimentally induced chronic seizures that had received repeated intraperitoneal administration of antiseizure drugs delivered in MC revealed similar widespread lesions. This study thus tested the hypothesis that chronic administration of intraperitoneal, but not PO, MC incites histologic lesions without effects on preclinical phenotype. Male CF-1 mice (n = 2-14/group) were randomized to receive either 6 weeks of twice weekly 0.5% MC or saline (intraperitoneal or PO) following induction of chronic seizures. Histology of a subset of mice rev...Continue Reading

References

Feb 1, 1994·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·D R Roth, G J Krinke
Aug 2, 2002·Epilepsy Research·Henrik KlitgaardYves Lamberty
Aug 5, 2003·Pathology International·Yoko KanekoKoh Nakazawa
Dec 29, 2005·Experimental Biology and Medicine·Hertzel SalmanMeir Djaldetti
Nov 30, 2006·International Journal of Toxicology·Shayne C GadHeide Robbe
Jul 6, 2010·Neurobiology of Disease·Stéphane AuvinRaman Sankar
Jan 6, 2011·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Carol KilkennyUNKNOWN National Centre for the Replacement, Refinement and Reduction of Amimals in Research
Apr 24, 2012·Neuropharmacology·Annamaria VezzaniRaymond J Dingledine
Dec 14, 2012·Journal of Virology·Matthew F CusickRobert S Fujinami
Mar 6, 2016·Journal of Neuropathology and Experimental Neurology·Jaycie L LoewenKaren S Wilcox
Jul 29, 2016·Epilepsia·Melissa L Barker-HaliskiH Steve White
Mar 18, 2017·Neurochemical Research·Melissa L Barker-HaliskiKaren S Wilcox
Jul 29, 2018·Intensive Care Medicine Experimental·Safiah H C MaiPatricia C Liaw
Jun 30, 2019·Expert Opinion on Drug Discovery·Melissa Barker-Haliski

❮ Previous
Next ❯

Citations

Jul 2, 2021·Frontiers in Immunology·Xinxin WangXuejing Wang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.