Rutin hydrate ameliorates cadmium chloride-induced spatial memory loss and neural apoptosis in rats by enhancing levels of acetylcholine, inhibiting JNK and ERK1/2 activation and activating mTOR signalling

Ghada A Abdel-Aleem; Eman F Khaleel

doi:10.1080/13813455.2017.1411370

Rutin hydrate ameliorates cadmium chloride-induced spatial memory loss and neural apoptosis in rats by enhancing levels of acetylcholine, inhibiting JNK and ERK1/2 activation and activating mTOR signalling

Arch Physiol Biochem. 2018 Oct;124(4):367-377. doi: 10.1080/13813455.2017.1411370. Epub 2017 Dec 7.

Authors

Ghada A Abdel-Aleem^{1

2}, Eman F Khaleel^{3

4}

Affiliations

¹ a Department of Medical Biochemistry, College of Medicine , King Khalid University , Abha , Saudi Arabia.
² b Department of Medical Biochemistry, Faculty of Medicine , Tanta University , Tanta , Egypt.
³ c Department of Medical Physiology, College of Medicine , King Khalid University , Abha , Saudi Arabia.
⁴ d Department of Medical Physiology, Faculty of Medicine , Cairo University , Cairo , Egypt.

PMID: 29214892
DOI: 10.1080/13813455.2017.1411370

Abstract

This study aimed at studying the potential neuroprotective effect of Rutin hydrate (RH) alone or in conjugation with α-tocopherol against cadmium chloride (CdCl₂)-induced neurotoxicity and cognitive impairment in rats and to investigate the mechanisms of action. Rats intoxicated with CdCl₂ were treated with the vehicle, RH, α-tocopherol or combined treatment were examined, and compared to control rats received vehicle or individual doses of either drug. Data confirmed that RH improves spatial memory function by increasing acetylcholine availability, boosting endogenous antioxidant potential, activating cell survival and inhibiting apoptotic pathways, an effect that is more effective when RH was conjugated with α-tocopherol. Mechanism of RH action includes activation of PP2A mediated inhibiting of ERK1/2 and JNK apoptotic pathways and inhibition of PTEN mediated activation of mTOR survival pathway. In conclusion, RH affords a potent neuroprotection against CdCl₂-induced brain damage and memory dysfunction and co-administration of α-tocopherol enhances its activity.

Keywords: Rutin hydrate; cadmium chloride; spatial memory-mTOR/Akt.

Publication types

Comparative Study

MeSH terms

Acetylcholine / agonists
Acetylcholine / metabolism
Animals
Antioxidants / therapeutic use
Apoptosis* / drug effects
Brain / drug effects
Brain / enzymology
Brain / metabolism*
Cadmium Chloride / antagonists & inhibitors
Cadmium Chloride / toxicity
Cadmium Poisoning / physiopathology
Cognitive Dysfunction / etiology
Cognitive Dysfunction / prevention & control
Dietary Supplements*
Enzyme Activation / drug effects
MAP Kinase Signaling System / drug effects
Male
Maze Learning / drug effects
Memory Disorders / etiology
Memory Disorders / prevention & control
Nerve Tissue Proteins / agonists
Nerve Tissue Proteins / antagonists & inhibitors
Nerve Tissue Proteins / metabolism
Neurons / drug effects
Neurons / enzymology
Neurons / metabolism*
Neuroprotective Agents / therapeutic use*
Neurotoxicity Syndromes / etiology
Neurotoxicity Syndromes / metabolism
Neurotoxicity Syndromes / prevention & control*
Rats, Wistar
Rutin / therapeutic use*
TOR Serine-Threonine Kinases / chemistry
TOR Serine-Threonine Kinases / metabolism
alpha-Tocopherol / therapeutic use

Substances

Antioxidants
Nerve Tissue Proteins
Neuroprotective Agents
Rutin
mTOR protein, rat
TOR Serine-Threonine Kinases
alpha-Tocopherol
Cadmium Chloride
Acetylcholine