The neurotoxic effect of long-term use of high-dose Pregabalin and the role of alpha tocopherol in amelioration: implication of MAPK signaling with oxidative stress and apoptosis

Taha, Sarah Hamed N.; Zaghloul, H S; Ali, Abla Abd El Rahman; Gaballah, Iman F.; Rashed, Laila Ahmed; Aboulhoda, Basma Emad

doi:10.1007/s00210-020-01875-5

Cited by 18 publications

(19 citation statements)

References 70 publications

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“…The current results showed that prolonged administration of high doses of pregabalin resulted in a significant decline in dopamine and norepinephrine. These results were in the same line with the study of Taha et al [16] which indicated a significant suppression in dopamine and norepinephrine following pregabalin administration in high doses.…”

Section: Discussionsupporting

confidence: 92%

“…Three pregabalin doses were used in this study:150, 300, and 600 mg/kg/day. The doses were given orally by intra-gastric gavage for 90 consecutive days to evaluate chronic abuse of pregabalin [16][17].…”

Section: Chemicalsmentioning

confidence: 99%

“…These doses are approximately equivalent to 1500 mg,3000 mg, and 6000 mg in humans which are the most commonly mentioned concentrations used by addicts in different studies and case reports known to produce the euphoric and dissociative effects desired by addicts, and as reported by abusers in case reports for recreational uses [16][17] according to the conversion equation [18]:…”

Section: Chemicalsmentioning

confidence: 99%

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Neurotoxic Assessment of Chronic Abuse of Pregabalin in Wistar Rats

Salem

Alsaedi

Alasmari

et al. 2021

JPRI

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Pregabalin (Lyrica) is an analog of the gamma-aminobutyric acid neurotransmitter, approved for the treatment of epilepsy, generalized anxiety disorder, neuropathic pain, and fibromyalgia. The possibility for abuse and/or dependence on pregabalin has risen recently. Pregabalin is controlled in many countries including Saudi Arabia. However, unofficial use of this substance is also on the increase. The purpose of this study is to assess the potential neurotoxic effects associated with overdose prolonged pregabalin supplementation. Forty male Wistar rats were divided into Group (1) normal control received distilled water, Group (2) received pregabalin (150mg/kg), Group (3) received pregabalin (300 mg/kg), and Group (4) received pregabalin (600 mg/kg). pregabalin consumption in different doses resulted in significant dysregulation in neurotransmitter release, upsurge oxidative stress markers via enhancing lipid peroxidation and depleting antioxidant markers. Also, pregabalin doses evoked brain tissue inflammation through elevating TNF-α, IL-1β, and MCP-1, Moreover promoted brain tissue apoptosis by activating caspase -3 and suppressed Bcl2. Pregabalin effects on the aforementioned parameters were dose-dependent. These findings could highlight the potential neurotoxic effect of prolonged abuse of pregabalin supplementation through dysregulating brain neurochemical, inflammatory, oxidant/antioxidant, and apoptotic mediators.

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Section: Discussionsupporting

confidence: 92%

Section: Chemicalsmentioning

confidence: 99%

Section: Chemicalsmentioning

confidence: 99%

See 1 more Smart Citation

Neurotoxic Assessment of Chronic Abuse of Pregabalin in Wistar Rats

Salem

Alsaedi

Alasmari

et al. 2021

JPRI

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“…Nader, Ateyya, El‐Shafey, & El‐Sherbeeny (2018) showed that PG increased hippocampal levels of MDA compared to controls. A previous study also showed a significant increase of MDA levels in cerebral cortex with administration of high doses of PG (150 and 300 mg kg ‐1 day ‐1 ; Taha et al., 2020). In the present study, the dose of PG (62 mg kg ‐1 day ‐1 ) did not significantly affected MDA levels; however, PG withdrawal led to a significant elevation of MDA levels which could be similar to opioid withdrawal where morphine administration elevated plasma MDA levels and its withdrawal (via naloxone) caused more increased MDA levels (Pinelli, Cighetti, & Trivulzio, 2008).…”

Section: Discussionmentioning

confidence: 74%

Pregabalin administration and withdrawal affect testicular structure and functions in rats

et al. 2020

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The aim of this prospective experimental study was to investigate the effects of pregabalin (PG) administration and withdrawal on testicular structures and functions in rats. A total of 24 male Wistar rats were divided into two groups (n = 12 each): a control group received normal saline, and PG‐treated group received 62 mg kg‐1 day‐1 PG for 2 months. Half the animals of each group were sacrificed for the collection of blood and testicular samples. The remaining animals were bred for another 2 months without treatment before collection of blood and testicular samples. PG administration decreased testosterone and increased luteinising hormone (LH) and follicle‐stimulating hormone (FSH) levels versus controls. PG withdrawal led to a decrease in both FSH and LH and an increase in testosterone levels versus saline withdrawal. Compared to controls, PG administration caused degeneration of seminiferous tubules and decreased the number of spermatogenic but increased the number of Leydig cells. After PG withdrawal, these cells showed a rebound reverse. Reduced glutathione levels increased with PG administration while PG withdrawal increased malondialdehyde levels. Conclusion: PG administration affected testicular morphometry, gonadotrophic and sex hormones; however, there was a rebound reversal in all these parameters and a significant oxidative stress in PG withdrawal.

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“…That is to say, from the laboratory perspective, the GPNs appear to be anti-addictive. Along those lines, even pregabalin (well-accepted as possessing a greater potential for abuse and dependence liability) has been recently shown in a rodent model to confer significant reduction in brain dopamine, glutamate, and norepinephrine [12].…”

Section: Association Does Not Equal Causality (Or Innocent Until Promentioning

confidence: 99%

Response to Comment on “Gabapentinoid Benefit and Risk Stratification: Mechanisms Over Myth”

McAnally

Bonnet

2021

Pain Ther

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The neurotoxic effect of long-term use of high-dose Pregabalin and the role of alpha tocopherol in amelioration: implication of MAPK signaling with oxidative stress and apoptosis

Cited by 18 publications

References 70 publications

Neurotoxic Assessment of Chronic Abuse of Pregabalin in Wistar Rats

Neurotoxic Assessment of Chronic Abuse of Pregabalin in Wistar Rats

Pregabalin administration and withdrawal affect testicular structure and functions in rats

Response to Comment on “Gabapentinoid Benefit and Risk Stratification: Mechanisms Over Myth”

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