Anthelmintics nitazoxanide protects against experimental hyperlipidemia and hepatic steatosis in hamsters and mice

Li, Fengfeng; Jiang, Man; Ma, Mingguo; Chen, Xuyang; Zhang, Yidan; Zhang, Yixin; Yu, Yuanyuan; Y, Cui; Chen, Jiahui; Zhao, Hui; Sun, Zeyu; Dong, De-Li

doi:10.1016/j.apsb.2021.09.009

Cited by 17 publications

(14 citation statements)

References 68 publications

(86 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Discussionmentioning

confidence: 99%

“…In our in vivo experiments studying the effect of nitazoxanide on Western diet (WD)-induced atherosclerosis in ApoE (À/À) mice, we also measured the serum lipid profile and the data were reported in our previous work (F. F. Li et al, 2022). Compared with wild type mice fed on a normal diet, the serum level of total cholesterol in WD-fed Apoe(À/À) mice increased, and the increase was reduced by nitazoxanide treatment (F. F. Li et al, 2022). Although an increase of serum cholesterol level is a major factor contributing to atherogenesis, comprehensively, we thought that the anti-atherosclerotic effects of nitazoxanide were through multiple mechanisms, including reducing the serum cholesterol level, inhibiting inflammation, inducing cellular autophagy, and inhibiting smooth muscle cell proliferation and migration (Figure 12).…”

Section: Discussionmentioning

confidence: 99%

“…In short, we speculate that nitazoxanide would be protective against atherosclerosis through inhibiting vascular smooth muscle cell proliferation and migration, and inhibiting macrophage NLRP3 inflammasome activation, in addition to improving hyperlipidaemia (F. F. Li. et al, 2022).…”

Section: Introductionmentioning

confidence: 94%

“…Furthermore, nitazoxanide showed a mitochondrial uncoupling effect in neurons (Amireddy et al, 2017). Our previous study demonstrated that nitazoxanide and tizoxanide induced mitochondrial uncoupling and activated AMPK in HepG2 cells in vitro and oral nitazoxanide improved experimental hyperlipidaemia in vivo (F. F. Li et al, 2022). In short, we speculate that nitazoxanide would be protective against atherosclerosis through inhibiting vascular smooth muscle cell proliferation and migration, and inhibiting macrophage NLRP3 inflammasome activation, in addition to improving hyperlipidaemia (F. F. Li.…”

Section: Introductionmentioning

confidence: 96%

See 3 more Smart Citations

Repurposing nitazoxanide as a novel anti‐atherosclerotic drug based on mitochondrial uncoupling mechanisms

et al. 2022

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

Background and Purpose The anthelmintic drug nitazoxanide has a mitochondrial uncoupling effect. Mitochondrial uncouplers have been proven to inhibit smooth muscle cell proliferation and migration, inhibit NLRP3 inflammasome activation of macrophages and improve dyslipidaemia. Therefore, we aimed to demonstrate that nitazoxanide would protect against atherosclerosis. Experimental Approach The mitochondrial oxygen consumption of cells was measured by using the high‐resolution respirometry system, Oxygraph‐2K. The proliferation and migration of A10 cells were measured by using Edu immunofluorescence staining, wound‐induced migration and the Boyden chamber assay. Protein levels were measured by using the western blot technique. ApoE (−/−) mice were fed with a Western diet to establish an atherosclerotic model in vivo. Key Results The in vitro experiments showed that nitazoxanide and tizoxanide had a mitochondrial uncoupling effect and activated cellular AMPK. Nitazoxanide and tizoxanide inhibited serum‐ and PDGF‐induced proliferation and migration of A10 cells. Nitazoxanide and tizoxanide inhibited NLRP3 inflammasome activation in RAW264.7 macrophages, the mechanism by which involved the AMPK/IκBα/NF‐κB pathway. Nitazoxanide and tizoxanide also induced autophagy in A10 cells and RAW264.7 macrophages. The in vivo experiments demonstrated that oral administration of nitazoxanide reduced the increase in serum IL‐1β and IL‐6 levels and suppressed atherosclerosis in Western diet‐fed ApoE (−/−) mice. Conclusion and Implications Nitazoxanide inhibits the formation of atherosclerotic plaques in ApoE (−/−) mice fed on a Western diet. In view of nitazoxanide being an antiprotozoal drug already approved by the FDA, we propose it as a novel anti‐atherosclerotic drug with clinical translational potential.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 96%

See 2 more Smart Citations

Repurposing nitazoxanide as a novel anti‐atherosclerotic drug based on mitochondrial uncoupling mechanisms

et al. 2022

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Nitazoxanide (Alinia ® ) is an FDA-approved broad-spectrum thiazolide antiprotozoal and antiparasitic agent, lately reported to be a potent AMPK activator and inhibitor of HSC activation. In experimental studies in mice, nitazoxanide (100 mg/kg/d) attenuated dyslipidaemia, liver steatosis [ 204 ], fibrosis, inflammation, and HCB, demonstrating synergistic effects with the pan-PPAR agonist elafibranor [ 205 ]. Moreover, the anti-anaerobic activity of nitazoxanide may determine its use in preventing the recurrence of hepatic encephalopathy as a viable alternative to rifaximin (NCT04161053) [ 206 ].…”

Section: Other Agentsmentioning

confidence: 99%

Pharmacotherapy for Non-Alcoholic Fatty Liver Disease: Emerging Targets and Drug Candidates

2022

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD), or metabolic (dysfunction)-associated fatty liver disease (MAFLD), is characterized by high global incidence and prevalence, a tight association with common metabolic comorbidities, and a substantial risk of progression and associated mortality. Despite the increasingly high medical and socioeconomic burden of NAFLD, the lack of approved pharmacotherapy regimens remains an unsolved issue. In this paper, we aimed to provide an update on the rapidly changing therapeutic landscape and highlight the major novel approaches to the treatment of this disease. In addition to describing the biomolecules and pathways identified as upcoming pharmacological targets for NAFLD, we reviewed the current status of drug discovery and development pipeline with a special focus on recent evidence from clinical trials.

show abstract

Thiazole, a privileged scaffold in drug discovery

Alam

2023

Privileged Scaffolds in Drug Discovery

View full text Add to dashboard Cite

Anthelmintics nitazoxanide protects against experimental hyperlipidemia and hepatic steatosis in hamsters and mice

Cited by 17 publications

References 68 publications

Repurposing nitazoxanide as a novel anti‐atherosclerotic drug based on mitochondrial uncoupling mechanisms

Repurposing nitazoxanide as a novel anti‐atherosclerotic drug based on mitochondrial uncoupling mechanisms

Pharmacotherapy for Non-Alcoholic Fatty Liver Disease: Emerging Targets and Drug Candidates

Thiazole, a privileged scaffold in drug discovery

Contact Info

Product

Resources

About