Multiple toxicity studies of trehalose in mice by intragastric administration

Liu, Mingyuan; Zhang, Meishuo; Ye, Haiqing; Lin, Songyi; Yang, Yi; Wang, Liying; Jones, Gregory S.; Trang, Hung K.

doi:10.1016/j.foodchem.2012.09.031

Cited by 21 publications

(22 citation statements)

References 12 publications

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“…The trehalose + MPTPp group were provided 1% trehalose in the water bottle and MPTP and probenecid injections identical to that described above. In previous studies, oral intake of up to 7.2 mg trehalose/kg body weight caused only a mild decrease in food intake, but no other signs of clinical toxicity in male mice [35,36]; thus, the 1% solution used here was well below a concentration which might cause toxicity. Mice were assigned to treatment groups (n = 10/group) based on their PND 21 body weight, such that all groups had approximately equal body weights.…”

Section: Mptpp and Trehalose Treatmentmentioning

confidence: 55%

“…However, that the group exposed only to trehalose (i.e., TRE) would perform more poorly than the CON group is surprising. The dose of trehalose used here is far lower than that which might cause any overt signs of toxicity [35,36] and the poor motor coordination was the only significant behavioral alteration exhibited by the TRE group. Thus, this potential effect awaits replication.…”

Section: Discussionmentioning

confidence: 82%

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Chronic MPTP treatment produces hyperactivity in male mice which is not alleviated by concurrent trehalose treatment

Ferguson

Law

Sarkar

2015

Behavioural Brain Research

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Section: Mptpp and Trehalose Treatmentmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 82%

Chronic MPTP treatment produces hyperactivity in male mice which is not alleviated by concurrent trehalose treatment

Ferguson

Law

Sarkar

2015

Behavioural Brain Research

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“…The heart, liver, spleen, kidney and testis were weighed, and the weights were recorded. The organ coefficients were calculated by eqn (2): 30 Organ coefficient ðg=100 gÞ ¼ Organ weight ðgÞ Rat body weight ðgÞ Â 100 (2)…”

Section: Preparation Of Aos-iron Complexmentioning

confidence: 99%

Effectiveness of AOS–iron on iron deficiency anemia in rats

Huang

Liu

et al. 2019

RSC Adv.

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“…Importantly, trehalose is nontoxic. Daily administration of trehalose intragastrically at a level as high as 5 g per kg of body weight had no effect in mice as measured by body weight, food consumption, sperm abnormality test, bone marrow cell micronucleus assay, organ coefficients, or hematological parameters (23).…”

mentioning

confidence: 95%

Trehalose, an mTOR-Independent Inducer of Autophagy, Inhibits Human Cytomegalovirus Infection in Multiple Cell Types

Belzile

Sabalza

Craig

et al. 2016

J Virol

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Human cytomegalovirus (HCMV) is the major viral cause of birth defects and a serious problem in immunocompromised individuals and has been associated with atherosclerosis. Previous studies have shown that the induction of autophagy can inhibit the replication of several different types of DNA and RNA viruses. The goal of the work presented here was to determine whether constitutive activation of autophagy would also block replication of HCMV. Most prior studies have used agents that induce autophagy via inhibition of the mTOR pathway. However, since HCMV infection alters the sensitivity of mTOR kinase-containing complexes to inhibitors, we sought an alternative method of inducing autophagy. We chose to use trehalose, a nontoxic naturally occurring disaccharide that is found in plants, insects, microorganisms, and invertebrates but not in mammals and that induces autophagy by an mTOR-independent mechanism. Given the many different cell targets of HCMV, we proceeded to determine whether trehalose would inhibit HCMV infection in human fibroblasts, aortic artery endothelial cells, and neural cells derived from human embryonic stem cells. We found that in all of these cell types, trehalose induces autophagy and inhibits HCMV gene expression and production of cell-free virus. Treatment of HCMV-infected neural cells with trehalose also inhibited production of cell-associated virus and partially blocked the reduction in neurite growth and cytomegaly. These results suggest that activation of autophagy by the natural sugar trehalose or other safe mTOR-independent agents might provide a novel therapeutic approach for treating HCMV disease. IMPORTANCEHCMV infects multiple cell types in vivo, establishes lifelong persistence in the host, and can cause serious health problems for fetuses and immunocompromised individuals. HCMV, like all other persistent pathogens, has to finely tune its interplay with the host cellular machinery to replicate efficiently and evade detection by the immune system. In this study, we investigated whether modulation of autophagy, a host pathway necessary for the recycling of nutrients and removal of protein aggregates, misfolded proteins, and pathogens, could be used to target HCMV. We found that autophagy could be significantly increased by treatment with the nontoxic, natural disaccharide trehalose. Importantly, trehalose had a profound inhibitory effect on viral gene expression and strongly impaired viral spread. These data constitute a proof-of-concept for the use of natural products targeting host pathways rather than the virus itself, thus reducing the risk of the development of resistance to treatment. H uman cytomegalovirus (HCMV) infects multiple cell types, including endothelial, smooth muscle, epithelial, and fibroblast cells, monocytes/macrophages, bone marrow progenitor cells, and cells of the neural lineage, and establishes lifelong persistence in the host (for a review, see reference 1). Seroprevalence is high in the general population, and in most healthy individuals, the in...

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Multiple toxicity studies of trehalose in mice by intragastric administration

Cited by 21 publications

References 12 publications

Chronic MPTP treatment produces hyperactivity in male mice which is not alleviated by concurrent trehalose treatment

Chronic MPTP treatment produces hyperactivity in male mice which is not alleviated by concurrent trehalose treatment

Effectiveness of AOS–iron on iron deficiency anemia in rats

Trehalose, an mTOR-Independent Inducer of Autophagy, Inhibits Human Cytomegalovirus Infection in Multiple Cell Types

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