ABSTRACT
An animal model of chronic tympanic membrane (TM) perforation is needed for experiments on supporting healing of TM perforations. The basic fibroblast growth factor is important in TM wound healing. The object of this study was to investigate the efficacy of fibroblast growth factor receptor 1 (FGFR1) inhibition to arrest wound healing of experimental TM perforation. Bilateral instrumental myringotomies were performed in 12 rats. A specific inhibitor of the FGFR1 tyrosine kinase (SU5402) was applied to the left TM (2 mg/ml) and to the right TM (10 mg/ml) of each animal daily for 12 consecutive days. Thereafter, TMs were observed weekly for a total of 30 days. TM healing was delayed in a dose-dependent manner. We observed differences in the histologic parameters between both groups. SU 5402 is a strong inhibitor of TM healing but seems not to be suitable to create a chronic TM perforation in rat.
Subject(s)
Pyrroles/pharmacology , Receptor, Fibroblast Growth Factor, Type 1/antagonists & inhibitors , Tympanic Membrane Perforation/physiopathology , Wound Healing/drug effects , Animals , Dose-Response Relationship, Drug , Female , Male , Protein-Tyrosine Kinases/antagonists & inhibitors , Rats , Rats, Inbred Lew , Tympanic Membrane/pathology , Tympanic Membrane Perforation/pathologyABSTRACT
OBJECTIVES/HYPOTHESIS: It is generally assumed that glycemic control in diabetic patients is important in optimizing wound healing. The goal of this study was to examine tympanic membrane (TM) wound healing in spontaneously diabetic rats depending on the diabetic metabolic state compared to nondiabetic control animals. STUDY DESIGN: Prospective controlled study in experimental animals. METHODS: Right-sided myringotomy was performed in 20 normoglycemic rats, 17 well-compensated, and 23 poorly compensated diabetic rats. TMs were observed for a total of 3 weeks. Effect of diabetic metabolic state on the healing of the TMs was evaluated by closure rates and histology. RESULTS: Diabetic rats showed a significant delay in TM wound healing compared to the control group, but there were no significant differences between both diabetes groups. CONCLUSIONS: Glycemic control does not influence TM wound repair in an animal model of type 1 diabetes.
Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Type 1/pathology , Fructosamine/blood , Tympanic Membrane Perforation/pathology , Tympanic Membrane/pathology , Wound Healing/physiology , Animals , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/genetics , Rats , Rats, Inbred BBABSTRACT
Recently, a report on a bilateral tympanic membrane (TM) perforation in a patient after long-term treatment with erlotinib was published. The object of this study was to investigate the destructive potential of topical applied epidermal growth factor receptor (EGFR) inhibitors on wound healing of experimental TM perforation in rats by evaluating closure rates and histology. In 12 rats, erlotinib (10 mg/ml) was applied to one TM of each animal and cetuximab (5 mg/ml) to the other side daily for 12 consecutive days. Both the erlotinib group (11.8 days) and cetuximab group (9 days) had prolonged healing latencies compared to a reference value (7 days). We observed differences in the histologic parameters between both groups. Our results suggest that in normal TM, the inhibition of EGFR does not lead to a persistent perforation. However, in case of preexisting TM pathology, a spontaneous perforation in patients under long-term treatment of EGFR inhibitors seems to be possible.
Subject(s)
ErbB Receptors/antagonists & inhibitors , Protein Kinase Inhibitors/pharmacology , Tympanic Membrane Perforation/physiopathology , Tympanic Membrane/physiology , Wound Healing/drug effects , Administration, Topical , Animals , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal, Humanized , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cetuximab , Disease Models, Animal , ErbB Receptors/metabolism , Erlotinib Hydrochloride , Female , Male , Quinazolines/administration & dosage , Quinazolines/pharmacology , Rats , Rats, Inbred Lew , Tympanic Membrane/anatomy & histology , Tympanic Membrane/drug effects , Tympanic Membrane Perforation/pathologyABSTRACT
An animal model of chronic tympanic membrane (TM) perforation is needed for experiments on supporting wound healing of TM perforations. The epidermal growth factor receptor (EGFR) has been implicated in the regulation of wound healing. The object of this study was to investigate the efficacy of topical EGFR-inhibitor (erlotinib) to arrest wound healing of experimental TM perforation in rats. Bilateral instrumental myringotomies were performed in 13 male rats. A solution of erlotinib (10 mg/mL) was applied to one TM of each animal and vehicle only (control group) to the other side. The application procedure was repeated on both sides daily for 12 consecutive days. Thereafter, tympanic membranes were observed weekly for a total of 30 days. The mean healing period was found to be 12.1 days in the group with erlotinib and 6.4 days in the control group. The difference was significant. We observed differences in the histologic parameters between erlotinib group and control group. The inhibition of EGFR by topical application of erlotinib did delay the healing rate of myringotomies but seems not to be suitable to create a chronic TM perforation in rat.
