Oral administration of d-galactose induces cognitive impairments and oxidative damage in rats

Budni, Josiane; Pacheco, Robson; Silva, Sabrina da; Garcez, Michelle Lima; Mina, Francielle; Bellettini-Santos, Tatiani; Medeiros, Jesiel de; Voss, Bruna Constantino; Steckert, Amanda V.; Valvassori, Samira da Silva; Quevedo, Joao L De

doi:10.1016/j.bbr.2015.12.041

Cited by 53 publications

(35 citation statements)

References 61 publications

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“…At high levels, which can be induced by exogenous galactose load or endogenously due to its dysfunctional metabolism, galactose reacts with the free amines of amino acids in proteins and peptides and consequently forms advanced glycation end products which cause oxidative damage in the body [67]. Chronic exposure of mice or rats to parenteral galactose has been widely used as a model for age-related development of brain oxidative stress and cognitive impairment [68][69][70][71][72][73]. At first glance, these parenteral galactoseinduced effects might seem contradictory to the findings presented in this study.…”

Section: Discussionmentioning

confidence: 99%

“…It should also be kept in mind that a nutrient might generally have a more acceptable safety profile than a drug. Therefore, knowing the detrimental effects of high galactose levels [67][68][69][70][71][72], the safety profile of oral galactose should be well characterised, taking into account its blood level and the appropriate pathophysiological state which might be responsive to such a therapy.…”

Section: Theorymentioning

confidence: 99%

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Glucagon-like peptide-1 mediates effects of oral galactose in streptozotocin-induced rat model of sporadic Alzheimer’s disease

et al. 2018

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Section: Discussionmentioning

confidence: 99%

Section: Theorymentioning

confidence: 99%

Glucagon-like peptide-1 mediates effects of oral galactose in streptozotocin-induced rat model of sporadic Alzheimer’s disease

et al. 2018

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“… 3) ROS and advanced glycation products have been implicated in several age-related diseases like Alzheimer’s disease, diabetes mellitus, cancers and amyotrophic lateral sclerosis, etc. 4) …”

Section: Introductionmentioning

confidence: 99%

Evaluation of Acute and Chronic Effects of D-Galactose on Memory and Learning in Wistar Rats

Chogtu

Arivazhahan

Kunder

et al. 2018

Clin Psychopharmacol Neurosci

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ObjectiveD-galactose has been commonly used in rodent models to induce accelerated effects of aging, including those on learning, memory, and muscular tone and coordination. This is normally seen on chronic administration of D-galactose. However, there is minimal suggestive evidence on the short-term effects of the same. The aim of the study was to study the acute and chronic effects of D-galactose on learning and memory in Wistar rats.MethodsTwenty four male Wistar rats were randomly assigned to the control, standard (rivastigmine), oral D-galactose (200 mg/kg/day) and subcutaneous D-galactose (200 mg/kg/day) for a total duration of 8 weeks. Effects on learning and memory were assessed at 2 weeks, 4 weeks and 8 weeks by Morris water maze model and passive avoidance testing.ResultsBoth oral and subcutaneous D-galactose showed positive effects on learning and memory on acute dosing, whereas this beneficial effect was lost during chronic dosing.ConclusionShort-term administration of D-galactose showed positive effects, while long-term administration nullified these effects.

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“…Mice administered with oral or subcutaneous D-galactose, a reducing sugar that generates advanced glycation end products in vivo [3], are extensively used to mimic the aging process. This oxidative damage-induced aging model is accompanied by high-level thiobarbituric acid reactive substances (TBARS), low superoxide dismutase (SOD) activity in various tissues [4, 5], telomere loss and compromised telomerase activities in the hippocampus [6]. …”

Section: Introductionmentioning

confidence: 99%

Polyunsaturated fatty acids ameliorate aging via redox-telomere-antioncogene axis

et al. 2016

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Polyunsaturated fatty acids (PUFA), a group of nourishing and health-promoting nutrients, ameliorate age-related chronic diseases. However, how PUFA especially n-3 PUFA exert anti-aging functions remains poorly understood. Here we link fish oil, docosahexaenoic acid (DHA) and arachidonic acid (AA) to the aging etiology via a redox-telomere-antioncogene axis based on D-galactose-induced aging mice. Both fish oil and PUFA enhanced hepatic superoxide dismutase (SOD) and catalase activities and cardiac SOD activities within the range of 18%-46%, 26%-65% and 19%-58%, respectively, whereas reduced cerebral monoamine oxidase activity, plasma F2-isoprostane level and cerebral lipid peroxidation level by 56%-90%, 20%-79% and 16%-54%, respectively. Thus, PUFA improve the in vivo redox and oxidative stress induced aging process, which however does not exhibit a dose-dependent manner. Notably, both PUFA and fish oil effectively inactivated testicular telomerase and inhibited c-Myc-mediated telomerase reverse transcriptase expression, whereas n-3 PUFA rather than n-6 PUFA protected liver and testes against telomere shortening within the range of 13%-25% and 25%-27%, respectively. Therefore, n-3 PUFA may be better at inhibiting the DNA damage induced aging process. Surprisingly, only DHA significantly suppressed cellular senescence pathway evidenced by testicular antioncogene p16 and p53 expression. This work provides evident support for the crosstalk between PUFA especially n-3 PUFA and the aging process via maintaining the in vivo redox homeostasis, rescuing age-related telomere attrition and down-regulating the antioncogene expression.

show abstract

Oral administration of d-galactose induces cognitive impairments and oxidative damage in rats

Cited by 53 publications

References 61 publications

Glucagon-like peptide-1 mediates effects of oral galactose in streptozotocin-induced rat model of sporadic Alzheimer’s disease

Glucagon-like peptide-1 mediates effects of oral galactose in streptozotocin-induced rat model of sporadic Alzheimer’s disease

Evaluation of Acute and Chronic Effects of D-Galactose on Memory and Learning in Wistar Rats

Polyunsaturated fatty acids ameliorate aging via redox-telomere-antioncogene axis

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