The effects of tramadol administration on hippocampal cell apoptosis, learning and memory in adult rats and neuroprotective effects of crocin

Baghishani, Farideh; Mohammadipour, Abbas; Hosseinzadeh, H; Hosseini, Mahmoud; Ebrahimzadeh‐Bideskan, Alireza

doi:10.1007/s11011-018-0194-6

Cited by 69 publications

(49 citation statements)

References 48 publications

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“…In PC12 cells, crocin prevents cell apoptosis via increasing glutathione synthesis (16); meanwhile, in aging Wistar rats, crocin enhances their memory abilities, mainly through its anti-oxidant activities (17). In rats administered tramadol hydrochloride, crocin improves their learning and reduces memory impairment (18). However, no systematic study of the effects of crocin on AD, and its underlying mechanisms, has been reported.…”

Section: Introductionmentioning

confidence: 99%

Investigation of the neuroprotective effects of crocin via antioxidant activities in HT22 cells and in mice with Alzheimer's disease

Wang

Cai

et al. 2018

Int J Mol Med

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Due to its complex pathogenesis, the prevention and therapization of Alzheimer’s disease (AD) remains a serious challenge. Crocin, the main compound isolated from Crocus sativus L., demonstrates various pharmacological activities including anti-apoptotic properties. The present study investigated the neuroprotective effect of crocin and the underlying mechanisms. In l-glutamate-damaged HT22 cells, 3-h crocin pretreatment strongly enhanced the HT22 cell viability, reduced the apoptotic rate, mitigated mitochondrial dysfunction, suppressed intracellular reactive oxygen species (ROS) accumulation and Ca2+ overload compared with untreated cells. Additionally, crocin significantly decreased the expression levels of Bax, Bad and cleaved caspase-3 and increased the expression levels of B-cell lymphoma-extra large, phosphorylated (P-) protein kinase B and P-mammalian target of rapamycin compared with untreated cells. In mice with AD induced by d-galactose and aluminum trichloride, crocin substantially improved the cognition and memory abilities of the mice as measured by their coordination of movement in an open field test, and reduced their escape time in the Morris water maze test compared with untreated mice. Biochemical analysis confirmed that crocin was able to reduce the Aβ1-42 content in the mouse brains, increase the levels of glutathione peroxidase, superoxide dismutase, acetylcholine and choline acetyltransferase, and reduce the levels of ROS and acetylcholinesterase in the serum, cerebral cortex and hypothalamus compared with untreated mice. Immunohistochemical analysis demonstrated that crocin reduced Aβ1-42 deposition in the hippocampus of the brains of treated mice compared with untreated mice. In conclusion, crocin demonstrates good prospects in the treatment of AD through the oxidative stress-associated apoptosis signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Investigation of the neuroprotective effects of crocin via antioxidant activities in HT22 cells and in mice with Alzheimer's disease

Wang

Cai

et al. 2018

Int J Mol Med

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“…Tramadol is one of the opioid drugs that is extensively used as a pain-killer for chronic pain and cancers [10]. However, multiple tissue toxicities were reported for patients consuming tramadol medication several times a day [13][14][15][16][17]. Since tramadol like other opioids induces oxidative stress which alters cell structure causing apoptosis [21][22][23][24][25], the pomegranate was used in the current study as a protective agent based on its antioxidant activity [34,35,48,49].…”

Section: Discussionmentioning

confidence: 99%

“…Tramadol is used to reduce pain resulted from posttraumatic, obstetric, osteoarthritis, fibromyalgia, renal, biliary colic, and neuropathic pain [12]. However, multiple tissue toxicities were reported when tramadol was administrated [13][14][15][16][17], especially for patients consuming tramadol medication several times daily to relieve chronic pain. We and others have shown that tramadol induces testicular toxicity in adults [5,9,[18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Pomegranate Seeds Extract Possesses a Protective Effect against Tramadol-Induced Testicular Toxicity in Experimental Rats

Minisy

Shawki

Omri

et al. 2020

BioMed Research International

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Tramadol is a centrally acting opioid analgesic that is extensively used. The chronic exposure to tramadol induces oxidative stress and toxicity especially for patients consuming it several times a day. Previously, we and others reported that tramadol induces testicular damage in rats. This study was conducted to investigate the possible protective effect of pomegranate seed extract (PgSE) against tramadol-induced testicular damage in adult and adolescent rats. Male rats were orally treated with tramadol or in a combination with PgSE for three weeks. Testes were then dissected and analyzed. Histological and ultrastructural examinations indicated that tramadol induced many structural changes in the testes of adult and adolescent rats including hemorrhage of blood vessels, intercellular spaces, interstitial vacuoles, exfoliation of germ cells in lumen, cell apoptosis, chromatin degeneration of elongated spermatids, and malformation of sperm axonemes. Interestingly, these abnormalities were not observed in tramadol/PgSE cotreated rats. The morphometric analysis revealed that tramadol disrupted collagen metabolism by elevating testicular levels of collagen fibers but that was protected in tramadol/PgSE cotreatment at both ages. In addition, DNA ploidy revealed that S phase of the cell cycle was diminished when adult and adolescent rats were treated with tramadol. However, the S phase had a normal cell population in the cotreated adult rats, but adolescent rats had a lower population than controls. Furthermore, the phytochemistry of PgSE revealed a high content of total polyphenols and total flavonoids within this extract; besides, the DPPH free radical scavenging activity was high. In conclusion, this study indicated that PgSE has a prophylactic effect against tramadol-induced testicular damage in both adult and adolescent ages, although the tramadol toxicity was higher in adolescent age to be completely protected. This prophylactic effect might be due to the high antioxidant compounds within the pomegranate seeds.

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“…This is in line with the findings of similar studies. In a study, [48], discovered that treatment of rats with tramadol resulted in an inability of the rats to remember the location of the hidden platform in probe test of Morris Water Maze (MWM).…”

Section: Discussionmentioning

confidence: 99%

“…The effects of neurotoxicity of tramadol have been proven and continuous administration of tramadol has been shown to result in a weight loss of rats' brain [49]. Findings from some recent studies using rodent models have shown that tramadol administration can impair memory functions by activation of µ-opioid receptors [35,48]. Several studies have also indicated that chronic administration of tramadol can cause histological abnormalities such as increasing apoptosis in rat cerebral cortex which is associated with oxidative stress [50], induce seizures [51], lead to increased oxidative stress in various tissues such as the brain [52] and lead to decrease in the expression of some genes in the hippocampus [53].…”

Section: Discussionmentioning

confidence: 99%

Effects of Separate and Combined Chronic Ingestion of Codeine and Tramadol on Exploratory Learning Behaviour Among Male Albino Rats

Balogun¹,

Osuh²,

Olotu³

2020

AJAP

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Tramadol and codeine are opioids known to have effective analgesic effects and potentials for the possible development of tolerance and addiction. The recent increase in the use and abuse of these substances coupled with research evidence implicating the ability of these opioids to readily access opioid receptors in the central nervous system (CNS) is a source of research concern. This study, therefore, examined the effects of chronic exposure to codeine and tramadol on exploratory learning behaviour. Twenty-four (24) male albino rats weighing between 150-200g and 4-6 weeks old, collected from the University of Ibadan Veterinary animal farm were used for this study. They were divided into 4 experimental groups of codeine, tramadol, combined codeine and tramadol and control groups with 6 rats in each group. They were exposed to 8mg/kg of codeine, 20mg/kg of tramadol, combined 8mg/kg of codeine and 20mg/kg of tramadol, and normal saline for the codeine, tramadol, combined codeine and tramadol and control groups respectively for 28 days. The rats were administered with the drugs every other day and observed after each treatment day for exploratory learning behaviour using the T-maze. randomized block ANOVA showed a significant effect of codeine and tramadol on exploratory learning behaviour among male albino rats, f (3,67) = 19.08, p < 0.001, η2=.08. Male albino rats in the codeine treatment group significantly took more time exploring the maze (Mean = 176.64) than combined group (Mean =168.13), tramadol group (Mean =131.10) and control group (Mean =92.48). The mean differences were significant (p<.001). It was concluded that chronic exposure to tramadol and codeine has implications for exploratory learning and memory deficits.

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The effects of tramadol administration on hippocampal cell apoptosis, learning and memory in adult rats and neuroprotective effects of crocin

Cited by 69 publications

References 48 publications

Investigation of the neuroprotective effects of crocin via antioxidant activities in HT22 cells and in mice with Alzheimer's disease

Investigation of the neuroprotective effects of crocin via antioxidant activities in HT22 cells and in mice with Alzheimer's disease

Pomegranate Seeds Extract Possesses a Protective Effect against Tramadol-Induced Testicular Toxicity in Experimental Rats

Effects of Separate and Combined Chronic Ingestion of Codeine and Tramadol on Exploratory Learning Behaviour Among Male Albino Rats

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