The Effect of Systemic Delivery of Aminoguanidine versus Doxycycline on the Resorptive Phase of Alveolar Bone Following modified Widman Flap in Diabetic Rats: A Histopathological and Scanning Electron Microscope (SEM) study

Abstract

Objectives: Aminoguanidine (guanylhydrazinehydrochloride) is a drug that prevents many of the classical systemic complications of diabetes including diabetic osteopenia through its inhibitory activity on the accumulation of advanced glycation end -products (AGEs). The aim of the present study was to evaluate the effectiveness of aminoguanidine versus doxycycline in reducing alveolar bone resorption following mucoperiosteal flap in diabetic rats, using the conventional histopathology and scanning electron microscope (SEM).

Methods: Twenty-seven male albino rats were used in this study. Periodontal defects were induced experimentally on lower anterior teeth. All rats were subjected to induction of diabetes, by IV injection of the pancreatic B-cells toxin alloxan monohydrate. After eight weeks following the establishment of periodontal defects in all rats, the ligation was removed and 3 rats were scarified as negative control (group 1). The remaining animals were divided into three group based on treatment applied following mucoperiosteal flap surgery. Group 2 received saline treatment only, group 3 received doxycycline periostat (1.5 mg/kg/day) for 3 weeks, and group 4 received aminoguanidine (7.3 mmol/kg) for 3 weeks. The fasting glucose level was measured weekly post operatively. After 21 days all rats were sacrificed. Three anterior parts of the mandible of each group was prepared for histopathological examination and two parts were prepared for SEM.

Results: Aminoguanidine treated group (group 4) showed statistically significant increased new bone formation, higher number of osteoblasts and decrease osteoclasts number, resorptive lacunae and existing inflammatory cell infiltration as compared to positive control group (group 2) (P<0.05). Doxycycline was also effective in reducing bone loss as documental by histopathological study.

Conclusion: The present study showed that aminoguanidine was significantly effective in reducing alveolar bone loss and can modify the detrimental effects of diabetes in alveolar bone resorption.

Fig. (1)

Histopathlogical comparison of different treatment groups. a: negative control (group 1) showing irregular bone surface and resorptive lacunae (arrows), rounded osteoclasts with ruffled border (cross arrow) and vasodilation. b: positive control (group 2) showing alveolar bone surface is markedly irregular and many resorptive lacunae housing osteoclasts (arrows) and intense inflammatory cell infiltration. c: doxycycline group (group 3) showing nearly healthy periodontal ligament and mild inflammatory cell infiltrate (arrow). Note the line demarcating newly formed bone (NB) and old bone (OB). d: aminoguanidine group(group 4)showing healthy periodontal ligament and smooth surface of newly formed bone, Note the line demarcating newly formed bone and old bone(arrow). (H&E×400)

Fig. (2)

SEM. a: negative control (group 1) showing destruction of bone surface as different diameter pores and fractured parts of the surface ( Mic Mag× 2.000). b: positive control (group 2) showing narrowing of some pores while others still patent( Mic Mag× 1.000). c: doxycycline group (group 3) showing incomplete closure of some pores and granulated bone surface( Mic Mag× 500). d: aminoguanidine group (group 4) showing closure of all bony defects and fine granulated surface that resembles normal bone surface ( Mic Mag× 500)