Effects of Bisphosphonate Derivatives on Macrophage Function

Mian, M.; Benetti, D; Aloisi, R; Rosini, S; Fantozzi, Roberto

doi:10.1159/000139251

Cited by 9 publications

(2 citation statements)

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“…This inhibition of the Fenton reaction could explain the decrease in H 2 O 2 , MDA, and PC levels (64), and the increase in antioxidant enzyme activity (CAT, GPx, SOD). These results are in agreement with those of Mian et al (65) showing that gem-bisphosphonates could prevent serum ROS production.…”

Section: Discussionsupporting

confidence: 93%

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3‐Keto‐1,5‐bisphosphonates Alleviate Serum‐Oxidative Stress in the High‐fat Diet Induced Obesity in Rats

et al. 2015

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Obesity has become a leading global health problem owing to its strong association with a high incidence of oxidative stress. Many epidemiologic studies showed that an antioxidant supplementation decreases the state of oxidative stress. In the present work, a HFD-induced rat obesity and oxidative stress were used to investigate the link between fat deposition and serum-oxidative stress markers. We also studied the effect of a chronic administration of 3-keto-1,5-bisphosphonates 1 (a & b) (40 μg/kg/8 weeks/i.p.). Exposure of rats to HFD during 16 weeks induced fat deposition, weight gain and metabolic disruption characterized by an increase in cholesterol, triglyceride and glycemia levels, and a decrease in ionizable calcium and free iron concentrations. HFD also induced serum-oxidative stress status vocalized by an increase in ROS (H2 O2 ), MDA and PC levels, with a decrease in antioxidant enzyme activity (CAT, GPx, SOD). Importantly, 3-keto-1,5-bisphosphonates corrected all the deleterious effects of HFD treatment in vivo, but it failed to inhibit lipases in vitro and in vivo. These studies suggest that 3-keto-1,5-bisphosphonates 1 could be considered as safe antioxidant agents that should also find other potential biological applications.

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Section: Discussionsupporting

confidence: 93%

“…These results are in agreement with those of Mian et al . showing that gem ‐bisphosphonates could prevent serum ROS production.…”

Section: Discussionmentioning

confidence: 99%

3‐Keto‐1,5‐bisphosphonates Alleviate Serum‐Oxidative Stress in the High‐fat Diet Induced Obesity in Rats

et al. 2015

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Treatment for experimental autoimmune neuritis with clodronate (Bonefos)

et al. 2013

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Experimental autoimmune neuritis (EAN) serves as an animal model for human Gullain-Barre syndrome (GBS), an autoimmune disease causing demyelination and inflammation of peripheral nerves. Macrophages, which play a major role in this autoimmune inflammatory process, can be selectively targeted by high doses of bisphophonates. The goal of this study was to examine the effect of the bisphosphonate, clodronate, on the severity of the EAN model. EAN was induced in female adult rats by immunization with bovine peripheral myelin. A number of treatment protocols with clodronate were used based on the common dosage regimen of 20 mg/kg in humans starting with the appearance of clinical signs on day 10 post-immunization. The clinical parameters measured included a clinical score, a motor performance test performed on a Rotarod and body weight. The expression of the matrix metaloprotease (MMP-9) in the sciatic nerves was measured as a marker of inflammatory macrophages. Treatment with clodronate, 20 mg/kg daily and 40 mg/kg every 2 days, significantly reduced the disease severity (a 75% decrease in severity, p < 0.01 by ANOVA) as measured by the clinical score compared to controls. Performance on the Rotarod test and body weight confirmed the clinical score findings. MMP-9 expression levels were significantly lower in the sciatic nerves of clodronate-treated rats. The present findings support the efficiency of clodronate in inflammatory diseases of the peripheral nervous system. The mechanism of action includes inhibition of inflammatory macrophages. The results suggest the use of bisphosphonates be considered in humans with GBS.

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