Cytotoxicity models of Huntington’s disease and relevance of hormetic mechanisms: A critical assessment of experimental approaches and strategies

Calabrese, Edward J.; Bhatia, Tarun N.; Calabrese, Vittorio; Dhawan, Gaurav; Giordano, James; Hanekamp, Yannic N.; Kapoor, Rachna; Kozumbo, Walter J.; Leak, Rehana K.

doi:10.1016/j.phrs.2019.104371

Cited by 11 publications

(6 citation statements)

References 232 publications

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“…The precise knowledge of HD pathology mechanisms is lacking, which hinders the development of effective therapeutics for HD. Preclinical research on animal models of HD has led to the identification of diverse protective agents showing an effective reduction in pathology; however, most of the studies have been performed using the toxic HD models [ 292 ]. One observation of these studies is that treating HD animals with a protective agent before causing HD by toxic drug administration may not be the best way to prove its benefits in a neurodegenerative disease, which takes years to develop.…”

Section: Discussionmentioning

confidence: 99%

Neuroinflammation in Huntington’s Disease: A Starring Role for Astrocyte and Microglia

Saba

Couselo

Bruno

et al. 2022

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: Huntington’s disease (HD) is a neurodegenerative genetic disorder caused by a CAG repeat expansion in the huntingtin gene. HD causes motor, cognitive, and behavioral dysfunction. Since no existing treatment affects the course of this disease, new treatments are needed. Inflammation is frequently observed in HD patients before symptom onset. Neuroinflammation, characterized by the presence of reactive microglia and astrocytes and inflammatory factors within the brain, is also detected early. However, in comparison with other neurodegenerative diseases, the role of neuroinflammation in HD is much less known. Work has been dedicated to altered microglial and astrocytic functions in the context of HD, but less attention has been given to glial participation in neuroinflammation. This review describes evidence of inflammation in HD patients and animal models. It also discusses recent knowledge on neuroinflammation in HD, highlighting astrocyte and microglia involvement in the disease and considering anti-inflammatory therapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

Neuroinflammation in Huntington’s Disease: A Starring Role for Astrocyte and Microglia

Saba

Couselo

Bruno

et al. 2022

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“…The NMDR characterized by some xenobiotics at low concentrations is one of the major challenges in (eco)toxicological risk assessment of both micro-pollutant and macro-pollutant of environmental concern. Therefore, the standard methods used in establishing safe exposure limits for humans and the environment by extrapolation from high dose testing might not be applicable to NMDR [61,64,65]. Studies by Calabrese and Blain [48] and Calabrese and Baldwin [64] observed that more than 9,000 examples of hormetic effects by pesticides, pharmaceuticals, or radiation, and all were independent of dose for a particular substance.…”

Section: Discussionmentioning

confidence: 99%

Effect of Diuron on Embryo-Larval Development of Javanese Medaka (<em>Oryzias</em> <em>javanicus</em>, Bleeker 1854)

Ibrahim¹,

Zulkifli²,

Azmai³

et al. 2020

Preprint

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Some herbicides exert hormetic or biphasic non-monotonic dose-response (NMDR), which is one of the major challenges for ecological risk assessment (ERA) of pesticides pollution. In this study, fish embryo toxicity test (FET) with Javanese medaka (Oryzias javanicus) to sublethal concentration of diuron was determined. Inverted U-shape heart rate was observed at 3 days post-exposure (dpe) and 7 dpe. However, at 13 dpe the heart rate (104 ± 2.90 heartbeat/min.) decreased in 10.00 mg.L-1 exposed-embryos. At 20 dpe, hatchability and survival rate were reduced in 5.00 mg.L-1 and 10.00 mg.L-1 exposed groups. Hormetic developmental deformities were observed in embryo-larvae of Javanese medaka. The results revealed a biphasic effect of low concentrations of diuron on some morphological and physiological features of Javanese medaka embryo-larvae, which might be attributed to endocrine disruption of this herbicide. Further studies to support these effects were recommended.

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“…And comparing the concentration dependency, curcumin appears to have one order of magnitude lower potency against melanoma cells (Lagoa et al, 2020a). There are also hormetic (biphasic) dose responses and, in these cases, high doses pose the risk to mask/overwhelm the capacity to induce therapeutic effects (Calabrese et al, 2019).…”

Section: Multifactorial Actions Of Natural Compoundsmentioning

confidence: 99%

Towards the Development of Delivery Systems of Bioactive Compounds With Eyes Set on Pharmacokinetics

Silva

Marques‐da‐Silva

Lagoa

2021

Modeling and Control of Drug Delivery Systems

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Cytotoxicity models of Huntington’s disease and relevance of hormetic mechanisms: A critical assessment of experimental approaches and strategies

Cited by 11 publications

References 232 publications

Neuroinflammation in Huntington’s Disease: A Starring Role for Astrocyte and Microglia

Neuroinflammation in Huntington’s Disease: A Starring Role for Astrocyte and Microglia

Effect of Diuron on Embryo-Larval Development of Javanese Medaka (<em>Oryzias</em> <em>javanicus</em>, Bleeker 1854)

Towards the Development of Delivery Systems of Bioactive Compounds With Eyes Set on Pharmacokinetics

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