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ZJUS-B
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology)  2016, Vol. 17 Issue (1): 43-53    DOI: 10.1631/jzus.B1500065
Article     
L-Carnitine, but not coenzyme Q10, enhances the anti-osteoporotic effect of atorvastatin in ovariectomized rats
Hussam A. S. Murad1,2,?
Department of Pharmacology, Faculty of Medicine, Rabigh, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo 11562, Egypt
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Abstract  

Objective: Statins’ therapy in osteoporosis can aggravate muscle damage. This study was designed to assess which agent, L-carnitine or coenzyme Q10, could enhance the anti-osteoporotic effect of atorvastatin while antagonizing myopathy in ovariectomized rats. Methods: Forty-eight female Sprague Dawley rats were used; forty rats were ovariectomized while eight were sham-operated. Eight weeks post-ovariectomy, rats were divided into ovariectomized-untreated group and four ovariectomized-treated groups (n=8) which received by gavage (mg/(kg?d), for 8 weeks) 17β-estradiol (0.1), atorvastatin (50), atorvastatin (50)+L-carnitine (100), or atorvastatin (50)+coenzyme Q10 (20). At the end of therapy, bone mineral density (BMD), bone mineral content (BMC), and serum levels of bone metabolic markers (BMMs) and creatine kinase (CK) were measured. Femurs were used for studying the breaking strength and histopathological changes. Results: Treatment with atorvastatin+L-carnitine restored BMD, BMC, and bone strength to near normal levels. Estrogen therapy restored BMD and BMC to near normal levels, but failed to increase bone strength. Although atorvastatin and atorvastatin+coenzyme Q10 improved BMD, BMC, and bone strength, they failed to restore levels to normal. All treatments decreased BMMs and improved histopathological changes maximally with atorvastatin+L-carnitine which restored levels to near normal. Atorvastatin aggravated the ovariectomy-induced increase in CK level while estrogen, atorvastatin+L-carnitine, and atorvastatin+coenzyme Q10 decreased its level mainly with atorvastatin+L-carnitine which restored the level to near normal. Conclusions: Co-administration of L-carnitine, but not coenzyme Q10, enhances the anti-osteoporotic effect of atorvastatin while antagonizing myopathy in ovariectomized rats. This could be valuable in treatment of osteoporotic patients. However, further confirmatory studies are needed.

Key words： Atorvastatin      Coenzyme Q10      L-Carnitine      Ovariectomized     
Received: 17 March 2015      Published: 01 January 2016
Corresponding Authors: Hussam A. S. Murad   
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Hussam A. S. Murad. L-Carnitine, but not coenzyme Q10, enhances the anti-osteoporotic effect of atorvastatin in ovariectomized rats. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2016, 17(1): 43-53.

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http://www.zjujournals.com/xueshu/zjus-b/10.1631/jzus.B1500065     OR     http://www.zjujournals.com/xueshu/zjus-b/Y2016/V17/I1/43

Treatment Initial BW (g) Final BW (g)
NOVX 182.13±2.00 202.50±2.06
OVX 179.50±3.04 213.13±2.44*
OVX+E2 183.25±1.84 215.38±1.94*
OVX+AT 180.88±2.14 212.50±1.96*
OVX+AT+LC 178.25±1.62 212.75±1.74*
OVX+AT+CQ 185.38±2.07 214.75±2.88*
Table 1 Effect of treatments (for eight weeks) on body weight (BW) in OVX rats
Fig. 1 Effects of treatments (for eight weeks) on bone mineral density (BMD) (a), bone mineral content (BMC) (b), femur breaking strength (c), and percentage of trabecular bone (d) NOVX: non-ovariectomized; OVX: ovariectomized; E2: 17β-estradiol (0.1 mg/(kg?d)); AT: atorvastatin (50 mg/(kg?d)); LC: L-carnitine (100 mg/(kg?d)); CQ: coenzyme Q10 (20 mg/(kg?d)). * A significant difference (P<0.05) vs. NOVX; ** A significant difference (P<0.05) vs. OVX; *** A significant difference (P<0.05) for OVX+AT+LC vs. OVX+AT and OVX+AT+CQ (a?d) and also vs. OVX+E2 (d). Data are expressed as mean±SEM (n=8)
Fig. 2 Femurs in different rat groups stained with hematoxylin and eosin (a) NOVX (non-ovariectomized) rats showed intact and well-formed trabeculae (white arrow) with normal marrow spaces. (b) OVX (ovariectomized) rats showed an irregular and markedly deformed epiphyseal plate (white stars), decreased trabecular thickness (white arrow), and widened marrow spaces. (c, d, e, f) The treated groups with 17β-estradiol, atorvastatin, atorvastatin+L-carnitine, and atorvastatin+coenzyme Q10, respectively, showed increases in trabecular thickness (white arrows) and narrowing of the widened spaces with newly formed osteoid tissue (white triangles) maximally in the atorvastatin+L-carnitine group which is nearly normal with a regular epiphyseal plate (white stars)
Fig. 3 Effects of treatments (for eight weeks) on serum levels of bone alkaline phosphatase (BALP) (a), osteoprotegerin (OPG) (b), type I collagen C-telopeptide (CTX-1) (c), and creatine kinase (CK) (d) NOVX: non-ovariectomized; OVX: ovariectomized; E2: 17β-estradiol (0.1 mg/(kg?d)); AT: atorvastatin (50 mg/(kg?d)); LC: L-carnitine (100 mg/(kg?d)); CQ: coenzyme Q10 (20 mg/(kg?d)). * A significant difference (P<0.05) vs. NOVX; ** A significant difference (P<0.05) vs. OVX; *** A significant difference (P<0.05) for OVX+AT+LC vs. other treatments; # A significant increase (P<0.05) vs. OVX. Data are expressed as mean±SEM (n=8)
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