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Pennanen, Niina; Lapinjoki, Seppo; Urtti, Arto; Mönkkönen, Jukka

doi:10.1023/a:1016281608773

Cited by 185 publications

(32 citation statements)

References 24 publications

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“…This action is, however, at least partially attributed to the decreased viability of macrophages after the drug and LPS treatment, suggesting that the observed effect may be secondary, rather than a direct effect as produced, for example, by clodronate. 26 On the other hand, in contrast to aminobisphosphonates such as pamidronate 26 and alendronate (Mönkkönen et al, unpublished results), DNTP does not augment the LPS-induced cytokine secretion from macrophages. This increased cytokine secretion from macrophages is believed to cause the acute phase response observed in patients treated for the first time with aminobisphosphonates.…”

Section: Discussionmentioning

confidence: 97%

“…9 Previous studies demonstrated the effects of gem bisphosphonates such as etidronate, clodronate, and the nitrogen-containing pamidronate. [25][26][27] Stock solutions of DNTP and PiBP were prepared by dissolving the drugs in deionized water at a concentration of 60 mM. The pHs of the solutions were adjusted to 7.2 with sodium bicarbonate powder.…”

Section: Methodsmentioning

confidence: 99%

“…25 The effects of free DNTP on interleukin-6 (IL-6) and nitric oxide (NO) from bacterial lipopolysaccharide (LPS)-induced RAW 264 cells was studied as previously described. 26,27,30 In brief, the cells were plated on 96-well plates (2 × 10 5 cells/well) and allowed to adhere for 2 h. Then, the cells were treated with various concentrations of DNTP (1-1000 µM) overnight. The cells were washed free of drug, incubated with LPS at 10 µg/mL for an additional 24 h, and the cell supernatants were collected and assayed for IL-6 30 and NO.…”

Section: Methodsmentioning

confidence: 99%

“…26,27,30 In brief, the cells were plated on 96-well plates (2 × 10 5 cells/well) and allowed to adhere for 2 h. Then, the cells were treated with various concentrations of DNTP (1-1000 µM) overnight. The cells were washed free of drug, incubated with LPS at 10 µg/mL for an additional 24 h, and the cell supernatants were collected and assayed for IL-6 30 and NO. 27 The cell viability was evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay (Sigma, St. Louis, MO) after the drug treatment and after the LPS induction.…”

Section: Methodsmentioning

confidence: 99%

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In Vitro and In Vivo Effects of Tetrakisphosphonates on Bone Resorption, Tumor Osteolysis, Ectopic Calcification, and Macrophages

Gelder

Breuer

Schlossman

et al. 1997

Journal of Pharmaceutical Sciences

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The biological effects of bisphosphonates in calcium-related disorders are attributed to the incorporation of the bisphosphonates in bone, enabling direct interaction with osteoclasts and/or osteoblasts. The high accumulation of bisphosphonates in bone, due to their high affinity to hydroxyapatite (HAP), is essential for mediating in vitro and in vivo activity. In this study we examined the activity of tetrakisphosphonates, molecules containing two P-C-P type bisphosphonate moieties connected by a carbon chain. The novel compounds were examined in a battery of in vitro and in vivo models including HAP formation and dissolution, ectopic calcification, bone resorption, tumor osteolysis, and of macrophage-like cells (anti- or pro-inflammatory properties). The inhibition of ectopic calcification was ranked as follows: geminal bisphosphonates > bisacylphosphonates > tetrakisphosphonates. Pamidronate, but not the tetrakisphosphonates, was an effective antiosteolytic agent. Neither DNTP (tetrasodium 1,9-dihydroxynonane 1,1,9,9-tetrakisphosphonate) nor the bisacylphosphonate, PiBP (pimeloylbisphosphonate) seem to possess strong macrophage suppressive or inductive effects and can be considered to be relatively inactive in terms of anti- or pro-inflammatory action. A significant anticalcification effect was caused by various phosphonates, such as the tetrakisphosphonates, but DNTP, a tetrakisphosphonate, was found toxic as it impeded somatic growth and bone development.

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Section: Discussionmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

In Vitro and In Vivo Effects of Tetrakisphosphonates on Bone Resorption, Tumor Osteolysis, Ectopic Calcification, and Macrophages

Gelder

Breuer

Schlossman

et al. 1997

Journal of Pharmaceutical Sciences

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“…Clodronate-liposome selectively depleted macrophages from tissue by competing with ATP (van Rooijen and Sanders, 1994). When administered intravenously, liposomes are delivered to phagocytic cells of the mononuclear phagocyte system, and clodronate is released intracellularly, which destroys these phagocytic cells (Pennanen et al, 1995;Day et al, 2005;Jo et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Clodronate-superparamagnetic iron oxide-containing liposomes attenuate renal injury in rats with severe acute pancreatitis

Dang

Zeng

Wang

et al. 2014

J. Zhejiang Univ. Sci. B

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Background and objective: It has been shown that macrophages play an important role in the development of severe acute pancreatitis (SAP), and eventually lead to multiple organ failure (MOF). Clodronate-liposome selectively depleted macrophages. This study was to investigate the role of renal macrophage infiltration in acute renal injury in rats with SAP and to evaluate the potential of superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) for diagnosis. Methods: Superparamagnetic Fe 3 O 4 nanoparticles were prepared by chemical coprecipitation. SPIO-liposomes and SPIO-clodronate-liposomes were prepared by the thin film method. SAP models were prepared by injection of sodium taurocholate into the subcapsular space of rat pancreas. Sprague-Dawley rats were randomly divided into a control group, SAP plus SPIO-liposome (P) group, and SAP plus SPIO-clodronatecontaining liposome (T) group. Kidney injury was evaluated by T2-weighted MRI scan. The levels of serum amylase (SAM), blood urea nitrogen (BUN), and serum creatinine (SCr) were measured by an automated enzymatic method. Serum tumor necrosis factor-α (TNF-α) was measured by enzyme-linked immunosorbent assay (ELISA). Pathological changes in the pancreas and kidney were observed using hematoxylin and eosin (H&E) staining, while cell apoptosis was detected with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. In addition, the macrophage markers (CD68) of the renal tissue were detected with immunohistochemistry. Results: The pathological changes in the pancreas and kidneys of rats in the T group were milder than those in the P group. The MRI signal intensity of the kidneys in the P and T groups was significantly lower than that in the control group. There were significant changes in the two experimental groups (P<0.01). The levels of SAM, Bun, SCr, and TNF-α in rats in the P group were higher than those in the control group (P<0.01) and in the T group (P<0.01). The apoptosis of the kidney in the T group was higher than that in the P group at 2 and 6 h (P<0.01). Conclusions: Clodronate-containing liposomes protected against renal injury in SAP rats, and SPIO can be used as a tracer for MRI examination to detect renal injury in SAP rats. SPIO-aided MRI provided an efficient non-invasive way to monitor the migration of macrophages after renal injury in rats with SAP.

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Attenuation of the Acute-Phase Response in Thermally Injured Rats by Cholesterol-Containing Cationic Liposomes Used as a Delivery System for Gene Therapy

et al. 1999

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Cholesterol-containing cationic liposomes alone modulate the acute-phase response and cytokine expression in thermally injured rats and are an effective delivery system for gene therapy in trauma. Setting: Laboratory. Intervention: Fifty-six adult male Sprague-Dawley rats with a full-thickness scald burn covering 60% of total body surface area were randomly divided into 2 groups to receive either intravenous injections of cholesterolcontaining cationic liposomes or saline (control). Main Outcome Measures: Body weights, muscle and liver dry-wet weights, serum levels of constitutive hepatic proteins, acute-phase protein levels, and cytokine levels were determined at 1, 2, 5, and 7 days after thermal injury. Results: Rats receiving cholesterol-containing cationic liposomes had less body weight loss, increased serum transferrin levels, and decreased serum ␣ 1-acid glycoprotein levels when compared with controls (PϽ.05). Serum interleukin 1␤ and tumor necrosis factor ␣ levels were decreased in rats receiving liposomes at 1 and 2 days after burn compared with controls (PϽ.05). Conclusions: These results suggest that cholesterolcontaining cationic liposomes alone may have a beneficial effect in modulating the hypermetabolic response after burn injury by decreasing type 1 acute-phase proteins and the expression of the proinflammatory cytokines interleukin 1␤ and tumor necrosis factor ␣. Therefore, cholesterol-containing cationic liposomes appear to be suitable as a delivery system for gene therapy in trauma.

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Untitled

Cited by 185 publications

References 24 publications

In Vitro and In Vivo Effects of Tetrakisphosphonates on Bone Resorption, Tumor Osteolysis, Ectopic Calcification, and Macrophages

In Vitro and In Vivo Effects of Tetrakisphosphonates on Bone Resorption, Tumor Osteolysis, Ectopic Calcification, and Macrophages

Clodronate-superparamagnetic iron oxide-containing liposomes attenuate renal injury in rats with severe acute pancreatitis

Attenuation of the Acute-Phase Response in Thermally Injured Rats by Cholesterol-Containing Cationic Liposomes Used as a Delivery System for Gene Therapy

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