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Mahmoud MAA, Saleh DO, Safar MM, et al. Chloroquine ameliorates bone loss induced by d-galactose in male rats via inhibition of ERK associated osteoclastogenesis and antioxidant effect. Toxicol Rep. 2021;8:366-375doi: 10.1016/j.toxrep.2021.02.007.
Mahmoud, M. A. A., Saleh, D. O., Safar, M. M., Agha, A. M., & Khattab, M. M. (2021). Chloroquine ameliorates bone loss induced by d-galactose in male rats via inhibition of ERK associated osteoclastogenesis and antioxidant effect. Toxicology reports, 8366-375. https://doi.org/10.1016/j.toxrep.2021.02.007
Mahmoud, Mohamed A Aziz, et al. "Chloroquine ameliorates bone loss induced by d-galactose in male rats via inhibition of ERK associated osteoclastogenesis and antioxidant effect." Toxicology reports vol. 8 (2021): 366-375. doi: https://doi.org/10.1016/j.toxrep.2021.02.007
Mahmoud MAA, Saleh DO, Safar MM, Agha AM, Khattab MM. Chloroquine ameliorates bone loss induced by d-galactose in male rats via inhibition of ERK associated osteoclastogenesis and antioxidant effect. Toxicol Rep. 2021 Feb 15;8:366-375. doi: 10.1016/j.toxrep.2021.02.007. eCollection 2021. PMID: 33665135; PMCID: PMC7905189.
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Toxicol Rep. 2021 Feb 15;8:366-375. doi: 10.1016/j.toxrep.2021.02.007. eCollection 2021.

Chloroquine ameliorates bone loss induced by d-galactose in male rats via inhibition of ERK associated osteoclastogenesis and antioxidant effect.

Toxicology reports

Mohamed A Aziz Mahmoud, Dalia O Saleh, Marwa M Safar, Azza M Agha, Mahmoud M Khattab

Affiliations

  1. Department of Pharmacology, Medical Division, National Research Centre, Giza, Egypt.
  2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
  3. Department of Pharmacology and Biochemistry, Faculty of Pharmacy, The British University in Egypt, Egypt.

PMID: 33665135 PMCID: PMC7905189 DOI: 10.1016/j.toxrep.2021.02.007

Abstract

Chloroquine (CQ); a lysosomotropic agent used for decade ago as anti-malarial, was tested against aging induced osteoporosis. Osteoporosis in male rats was induced using d-galactose (D-gal) as a reducing sugar at a dose of 200 mg/kg/day; i.p. Osteoporotic rats were orally treated with CQ (10 mg/kg/day) for four successive weeks. Bone densitometry of tibia and femur were evaluated. Bone formation biomarkers; osteoprotegrin (OPG), bone specific alkaline phosphatse (BALP), and osteocalcin (OCN), and bone resorption biomarker; receptor activator of nuclear factor kappa-B ligand (RANKL), cathepsin-k (CTSK), tartrate-resistant acid phosphatase (TRAP) were estimated. Moreover, the expression of extracellular regulated kinase (ERK) in bone was determined. CQ ameliorated the bone detrimental changes induced by d-galactose. It enhanced bone health as revealed by measurement of bone densitometry, halted the activation of receptor activator of nuclear factor kappa-B ligand (RANKL) and reduced bone manifestation of ERK. Furthermore, CQ treatment abated serum cathepsin-k (CTSK) and serum tartrate-resistant acid phosphatase (TRAP) thus inhibited osteoclastogenesis and consequently restored the RANKL/OPG ratio. CQ demonstrated an antioxidant effect in bone where it increased both Catalase (CAT) and Superoxide dismutase (SOD). These CQ preserving effect in rats treated with d-galactose were confirmed by the histopathological examination. The present study points to the potential therapeutic effect of CQ as anti-osteoporotic agent possibly through its antioxidant effects and suppression of ERK associated osteoclastogenesis.

© 2021 The Authors.

Keywords: Chloroquine; ERK; OPG; Osteoporosis; RANKL; Rats

Conflict of interest statement

The authors declare no conflict of interest.

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