Study of subchronic toxicity of the calcium hydroxyapatite

Abstract

Background: Calcium hydroxyapatite is the main mineral component in bones and dental tissue. Nowadays, hydroxyapatite is widely used in biomedical applications, including matrices to control drug release and material engineering of bone tissues. Oral administration of calcium hydroxyapatite can accelerate fracture healing and repair and even prevent osteoporosis. Aim: To study of subchronic oral toxicity of calcium hydroxyapatite. Materials and Methods: The evaluation of oral subchronic toxicity study was according to OECD guidelines number 407. Wistar rats were randomly divided into three groups of 10 animals each. Group 1 served as control and received a daily administration of distilled water. Groups 2 and 3 administered calcium hydroxyapatite doses of 1000 mg/kg/ and 2000 mg/kg body weight, for 45 days. The general condition, toxic signs and mortality were daily observed and recorded. The hematological and biochemical analysis were conducted on 46th days. On the 46th day, the experimental rats were sacrificed, and the liver, kidneys, heart, spleen, and stomach were carefully dissected out and fixed in 10 % buffered formalin solution. Preparations were prepared by fully automated procedures, cut into 5 µm thickness and stained with hematoxylin and eosin. All fields of tissue morphology were examined under an Olympus BX41 light microscope. Results: All the rats were healthy, there was no sign of toxicity or mortality observed in any of the groups. No statistically significant (p>0.05) difference was observed in the liver and kidney function (AST, ALT, alkaline phosphatase, creatinine and urea) in rats treated with calcium hydroxyapatite at doses of 1000 mg/kg and 2000 mg/kg for 45 days between the control and experimental groups. Histopathological examination results of the experimental and control groups showed that the liver, kidney, heart and spleen, stomach organs maintained their tissue structure as normal. Conclusions: The calcium hydroxyapatite did not present liver and renal toxic effects when administered orally to rats. Histopathological examination results of rats treated with calcium hydroxyapatite at doses of 1000 mg/kg and 2000 mg/ kg showed that slight interstitial calcification in the kidney tissue and at a dose of 2000 mg/kg showed that superficial gastric erosion.