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

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

doi:10.1016/j.toxrep.2021.02.007

Cited by 5 publications

(7 citation statements)

References 56 publications

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“…Our in vitro study demonstrated that D-gal and hyperinsulinism promoted osteoclast differentiation equally. Consistent with this finding an increased secretory activity of the osteoclasts has been well-established at either 8 weeks after the onset of D-gal injection- or long-term HFD consumption-induced osteoporosis, as indicated by an elevation of cathepsin K level in serum 41 , 53 – 55 . These previous findings suggested that either D-gal- or hyperinsulinism-induced increase in osteoclast number was mediated by the increased secretory activity of osteoclasts, resulting in increased osteoclast differentiation.…”

Section: Discussionsupporting

confidence: 72%

“…At week 8, D-gal plus HFD-induced aging and obesity both independently and synergistically stimulated the increases in serum CTX-I level and RANKL mRNA expression in the bone. Interestingly, the role of oxidative stress in the alteration of RANKL expression has been well-established in aging models 40 , 41 . Specifically, a prior study in rats revealed that 8 weeks of D-gal administration compromised the activity of antioxidant enzymes (superoxide dismutase and catalase) in serum, increased serum RANKL level, and increased osteoporosis 41 .…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, the role of oxidative stress in the alteration of RANKL expression has been well-established in aging models 40 , 41 . Specifically, a prior study in rats revealed that 8 weeks of D-gal administration compromised the activity of antioxidant enzymes (superoxide dismutase and catalase) in serum, increased serum RANKL level, and increased osteoporosis 41 . These findings suggested that both D-gal and HFD-induced increased oxidative stress was also associated with increased RANKL expression.…”

Section: Discussionmentioning

confidence: 99%

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D-galactose-induced aging aggravates obesity-induced bone dyshomeostasis

Imerb

Thonusin

Pratchayasakul

et al. 2022

Sci Rep

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We aimed to compare the time-course effect of D-galactose (D-gal)-induced aging, obesity, and their combined effects on bone homeostasis. Male Wistar rats were fed with either a normal diet (ND; n = 24) or a high-fat diet (HFD; n = 24) for 12 weeks. All rats were then injected with either vehicle or 150 mg/kg/day of D-gal for 4 or 8 weeks. Blood was collected to measure metabolic, aging, oxidative stress, and bone turnover parameters. Bone oxidative stress and inflammatory markers, as well as bone histomorphometry were also evaluated. Additionally, RAW 264.7 cells were incubated with either D-gal, insulin, or D-gal plus insulin to identify osteoclast differentiation capacity under the stimulation of receptor activator of nuclear factor κB ligand. At week 4, D-gal-induced aging significantly elevated serum malondialdehyde level and decreased trabecular thickness in ND- and HFD-fed rats, when compared to the control group. At week 8, D-gal-induced aging further elevated advanced glycation end products, increased bone inflammation and resorption, and significantly impaired bone microarchitecture in HFD-fed rats. The osteoclast number in vitro were increased in the D-gal, insulin, and combined groups to a similar extent. These findings suggest that aging aggravates bone dyshomeostasis in the obese condition in a time-dependent manner.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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D-galactose-induced aging aggravates obesity-induced bone dyshomeostasis

Imerb

Thonusin

Pratchayasakul

et al. 2022

Sci Rep

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“…Age‐related bone loss induced by d ‐galactose through the activation of RAS locally in skeletal tissues plays a pivotal role in bone remodeling and metabolism [23, 24]. In the current study, treatment with d ‐galactose dramatically augmented the expression of AT 1 R in bone over AT 2 R, which was consistent with a former study conducted by [5] in d ‐galactose‐induced aging in rats.…”

Section: Discussionsupporting

confidence: 91%

“…Data were statistically evaluated using one-way ANOVA followed by Tukey's multiple comparisons test. Differences were considered statistically significant when *P < 0.05 compared with the control group and @ P < 0.05 compared with Dgal-treated group pivotal role in bone remodeling and metabolism [23,24].…”

Section: Discussionmentioning

confidence: 99%

Telmisartan: An angiotensin receptor blocker regulates osteoclastogenesis via inhibition of the ERK triggering in osteoporotic male rats

Mahmoud

Safar

Agha

et al. 2022

Fundamemntal Clinical Pharma

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Great attention was recently given to the importance of RAS in controlling inflammatory bone diseases, following the discovery of its local existence in skeletal tissues. Local RAS was found to be expressed on osteoblastic and osteoclastic cells and to exert its action via angiotensin II (AngII) receptors, including angiotensin II type 1 receptor (AT 1 R) and angiotensin II type 2 receptors. Telmisartan (TLM), an AT 1 R blocker (ARBs), was investigated in the present study for its therapeutic effect on bone health in osteoporotic rats. D-Galactose, a reducing sugar at a dose of 200 mg/kg/day/i.p., was used to induce osteoporosis in male rats. TLM, at a dose of 5 mg/kg/day, was orally introduced in the osteoporotic rats for four consecutive weeks. Tibia and femur bone densitometry was estimated, bone formation and bone resorption biomarkers serum levels were measured, mineral content in blood was also valued, and finally the extracellular regulated kinase (ERK) expression in bone was determined. TLM considerably improved the deleterious effect of D-galactose on bone mineral density. It blunted serum bone-specific alkaline phosphatase and osteocalcin while elevating serum osteoprotegrin (OPG). On the other hand, TLM turned off the pronounced elevation in serum receptor activator of nuclear factor-κβ ligand (RANKL), tartrate-resistant acid phosphatase, and cathepsin K. Furthermore, it significantly hindered the bone expression of ERK which hampered osteoclastogenesis. AT 1 R inhibition abolished the rise in serum calcium and phosphorus and normalized serum superoxide dismutase and catalase. These TLM protective effects in D-galactose-treated rats were confirmed by the histopathological examination. The results all together denote the potential therapeutic value of ARBs therapy in osteoporosis. K E Y W O R D S angiotensin receptor blockerosteoporosis, D-galactose, extracellular regulated kinase, rats

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