Effect of D-003, a Mixture of High Molecular Weight Aliphatic Acids, on Glucocorticoid- and Lipopolysaccharides (LPS)-Induced Osteonecrosis

Overview

Journal Iran J Pharm Res

Publisher Brieflands

Specialty Pharmacology

Date 2013 Nov 20

PMID 24250554

Citations 2

Authors

Miriam Noa

Rosa Mas

Maikel Valle

Sarahi Mendoza

Nilda Mendoza

Affiliations

Soon will be listed here.

Abstract

Osteonecrosis (ON) is characterized through the impairment of osseous blood flow that leads to the collapse of femur head. Corticoid-induced ON in rats and lipopolysaccharide (LPS)-induced in rabbits are useful models to assess the efficacy of potential treatments on this disease. D-003 inhibits the mevalonate pathway, lipid peroxidation and prevents osteoporosis in rats through increasing the osteoclast apoptosis. This study investigated the effects of D-003 on corticoid- and LPS-induced ON in rats and rabbits. Corticoid-induced ON: Rats were randomized into five groups. A negative control and four groups treated with prednisolone 6 mg/Kg: a positive control and three treated with D-003 (5, 25 and 200 mg/Kg) for 80 days. All positive controls presented ON areas. D-003 significantly reduced the numbers and proportions of ON lesions, as compared to the positive control group. LPS-induced ON in rabbits: Rabbits were randomized into five groups: a negative control and four injected with a single intra-venous injection of LPS (10 μg/Kg) including a positive control and three with D-003 (5, 25 and 200 mg/Kg) for 30 days. ON was seen in all positive controls. The incidence of ON and the number of ON lesions in the groups treated with D-003 (25 and 200 mg/Kg) was significantly lower compared to the positive controls. LPS injection significantly increased the size of bone marrow fat cells in positive controls and such increase was significantly decreased by D-003. In conclusion, D-003 reduced ON lesions in corticoid-and LPS-induced ON and also the size of bone marrow fat cells in rabbits with LPS.

Citing Articles

5-Azacytidine and trichostatin A enhance the osteogenic differentiation of bone marrow mesenchymal stem cells isolated from steroid-induced avascular necrosis of the femoral head in rabbit.

Zhang P, Tao F, Li Q, Wu S, Fu B, Liu P J Biosci. 2019; 44(4).

PMID: 31502565

Anethole, a Medicinal Plant Compound, Decreases the Production of Pro-Inflammatory TNF-α and IL-1β in a Rat Model of LPS-Induced Periodontitis.

Moradi J, Abbasipour F, Zaringhalam J, Maleki B, Ziaee N, Khodadoustan A Iran J Pharm Res. 2015; 13(4):1319-25.

PMID: 25587321 PMC: 4232798.

References

Menendez R, Mas R, Amor A, Rodeiros I, Gonzalez R, Alfonso J . Inhibition of cholesterol biosynthesis in cultured fibroblasts by D003, a mixture of very long chain saturated fatty acids. Pharmacol Res. 2001; 44(4):299-304. DOI: 10.1006/phrs.2001.0851. View

Matsumoto T, Kitamura K, Ichiseki T, Kaneuji A, Sugimori T . [Oxidative stress on idiopathic osteonecrosis]. Clin Calcium. 2007; 17(6):887-91. DOI: CliCa0706887891. View

Irisa T, Yamamoto T, Miyanishi K, Yamashita A, Iwamoto Y, Sugioka Y . Osteonecrosis induced by a single administration of low-dose lipopolysaccharide in rabbits. Bone. 2001; 28(6):641-9. DOI: 10.1016/s8756-3282(01)00460-4. View

Masuhara K, Nakata K, Yamasaki S, Miki H, Yoshikawa H . Involvement of platelet activation in experimental osteonecrosis in rabbits. Int J Exp Pathol. 2001; 82(5):303-8. PMC: 2517778. DOI: 10.1046/j.1365-2613.2001.00202.x. View

Ortoft G, Oxlund H . Qualitative alterations of cortical bone in female rats after long-term administration of growth hormone and glucocorticoid. Bone. 1996; 18(6):581-90. DOI: 10.1016/8756-3282(96)00077-4. View

Kabata T, Kubo T, Matsumoto T, Hirata T, Fujioka M, Takahashi K . Onset of steroid-induced osteonecrosis in rabbits and its relationship to hyperlipaemia and increased free fatty acids. Rheumatology (Oxford). 2005; 44(10):1233-7. DOI: 10.1093/rheumatology/keh721. View

Boss J, Misselevich I . Osteonecrosis of the femoral head of laboratory animals: the lessons learned from a comparative study of osteonecrosis in man and experimental animals. Vet Pathol. 2003; 40(4):345-54. DOI: 10.1354/vp.40-4-345. View

Meizer R, Radda C, Stolz G, Kotsaris S, Petje G, Krasny C . MRI-controlled analysis of 104 patients with painful bone marrow edema in different joint localizations treated with the prostacyclin analogue iloprost. Wien Klin Wochenschr. 2005; 117(7-8):278-86. DOI: 10.1007/s00508-005-0326-y. View

Marker D, Seyler T, McGrath M, Delanois R, Ulrich S, Mont M . Treatment of early stage osteonecrosis of the femoral head. J Bone Joint Surg Am. 2008; 90 Suppl 4:175-87. DOI: 10.2106/JBJS.H.00671. View

10.

Noa M, Mendoza S, Mas R, Mendoza N, Goicochea E . Long-term effects of D-003, a mixture of high molecular weight acids from sugarcane wax, on bones of ovariectomized rats: a one year study. Pharmazie. 2008; 63(6):486-8. View

11.

Miyanishi K, Yamamoto T, Irisa T, Motomura G, Jingushi S, Sueishi K . Effects of different corticosteroids on the development of osteonecrosis in rabbits. Rheumatology (Oxford). 2004; 44(3):332-6. DOI: 10.1093/rheumatology/keh505. View

12.

Molina V, Arruzazabala M, Carbajal D, Mas R, Valdes S . Antiplatelet and antithrombotic effect of D-003. Pharmacol Res. 2000; 42(2):137-43. DOI: 10.1006/phrs.2000.0664. View

13.

Sen R . Management of avascular necrosis of femoral head at pre-collapse stage. Indian J Orthop. 2009; 43(1):6-16. PMC: 2739499. DOI: 10.4103/0019-5413.45318. View

14.

Wang G, Cui Q, Balian G . The Nicolas Andry award. The pathogenesis and prevention of steroid-induced osteonecrosis. Clin Orthop Relat Res. 2000; (370):295-310. DOI: 10.1097/00003086-200001000-00030. View

15.

Miyanishi K, Yamamoto T, Irisa T, Yamashita A, Jingushi S, Noguchi Y . Bone marrow fat cell enlargement and a rise in intraosseous pressure in steroid-treated rabbits with osteonecrosis. Bone. 2002; 30(1):185-90. DOI: 10.1016/s8756-3282(01)00663-9. View

16.

Menendez R, Mas R, Perez J, Gonzalez R, Jimenez S . Oral administration of D-003, a mixture of very long chain fatty acids prevents casein-induced endogenous hypercholesterolemia in rabbits. Can J Physiol Pharmacol. 2004; 82(1):22-9. DOI: 10.1139/y03-123. View

17.

Wang Y, Yin L, Li Y, Liu P, Cui Q . Preventive effects of puerarin on alcohol-induced osteonecrosis. Clin Orthop Relat Res. 2008; 466(5):1059-67. PMC: 2311465. DOI: 10.1007/s11999-008-0178-7. View

18.

Mendoza S, Noa M, Mas R, Mendoza N . Comparison of the effects of D-003, a mixture of high-molecular-weight aliphatic acids from sugarcane wax, and pravastatin on bones and osteoclast apoptosis of ovariectomized rats. Drugs Exp Clin Res. 2006; 31(5-6):181-91. View

19.

Castano G, Menendez R, Mas R, Ledon N, Fernandez J, Perez J . Effects of d-003, a new hypocholesterolaemic and antiplatelet compound, on lipid profile and lipid peroxidation in healthy volunteers. Clin Drug Investig. 2013; 23(3):193-203. DOI: 10.2165/00044011-200323030-00005. View

20.

Motomura G, Yamamoto T, Miyanishi K, Kondo K, Hirota Y, Iwamoto Y . Risk factors for developing osteonecrosis after prophylaxis in steroid-treated rabbits. J Rheumatol. 2008; 35(12):2391-4. DOI: 10.3899/jrheum.080416. View