Dopaminergic neurotoxic effects of 3-TFMPP derivatives

Majrashi, Mohammed; Almaghrabi, Mohammed; Fadan, Maali; Fujihashi, Ayaka; Lee, Wooseok; DeRuiter, Jack; Clark, Charles R.; Dhanasekaran, Muralikrishnan

doi:10.1016/j.lfs.2018.07.052

Cited by 16 publications

(22 citation statements)

References 73 publications

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“…The contribution of these individual compounds to the observed clinical manifestations remains unclear, but piperazines and MDMA may elicit additive or synergistic toxicity. In vitro, piperazine designer drugs have been reported to upregulate key enzymes of cholesterol biosynthesis, induce oxidative stress, disrupt mitochondrial function, and activate apoptosis pathways, all of which may potentially contribute to clinical toxicity (Arbo et al 2016a, b;Dias da Silva et al 2017;Dias-da-Silva et al 2015;Majrashi et al 2018).…”

Section: Adverse Effects Of Piperazinesmentioning

confidence: 99%

Designer drugs: mechanism of action and adverse effects

2020

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Psychoactive substances with chemical structures or pharmacological profiles that are similar to traditional drugs of abuse continue to emerge on the recreational drug market. Internet vendors may at least temporarily sell these so-called designer drugs without adhering to legal statutes or facing legal consequences. Overall, the mechanism of action and adverse effects of designer drugs are similar to traditional drugs of abuse. Stimulants, such as amphetamines and cathinones, primarily interact with monoamine transporters and mostly induce sympathomimetic adverse effects. Agonism at l-opioid receptors and c-aminobutyric acid-A (GABA A) or GABA B receptors mediates the pharmacological effects of sedatives, which may induce cardiorespiratory depression. Dissociative designer drugs primarily act as N-methyl-D-aspartate receptor antagonists and pose similar health risks as the medically approved dissociative anesthetic ketamine. The cannabinoid type 1 (CB 1) receptor is thought to drive the psychoactive effects of synthetic cannabinoids, which are associated with a less desirable effect profile and more severe adverse effects compared with cannabis. Serotonergic 5-hydroxytryptamine-2A (5-HT 2A) receptors mediate alterations of perception and cognition that are induced by serotonergic psychedelics. Because of their novelty, designer drugs may remain undetected by routine drug screening, thus hampering evaluations of adverse effects. Intoxication reports suggest that several designer drugs are used concurrently, posing a high risk for severe adverse effects and even death.

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Section: Adverse Effects Of Piperazinesmentioning

confidence: 99%

Designer drugs: mechanism of action and adverse effects

2020

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“…ROS formed and was normalized to total protein content (relative fluorescence unit/mg protein). Results were expressed as (%) change as compared to the control (Alhowail et al, 2019;Katz et al, 2018;Majrashi et al, 2018).…”

Section: Generation Of Reactive Oxygen Species (Ros)mentioning

confidence: 99%

Effects of prenatal synthetic cannabinoid exposure on the cerebellum of adolescent rat offspring

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Majrashi

Fujihashi

et al. 2021

Heliyon

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Cannabis is the most commonly used illicit drug worldwide. Recently, cannabis use among young pregnant women has greatly increased. However, prenatal cannabinoid exposure leads to long-lasting cognitive, motor, and behavioral deficits in the offspring and alterations in neural circuitry through various mechanisms. Although these effects have been studied in the hippocampus, the effects of prenatal cannabinoid exposure on the cerebellum are not well elucidated. The cerebellum plays an important role in balance and motor control, as well as cognitive functions such as attention, language, and procedural memories. The aim of this study was to investigate the effects of prenatal cannabinoid exposure on the cerebellum of adolescent offspring. Pregnant rats were treated with synthetic cannabinoid agonist WIN55,212-2, and the offspring were evaluated for various cerebellar markers of oxidative stress, mitochondrial function, and apoptosis. Additionally, signaling proteins associated with glutamate dependent synaptic plasticity were examined. Administration of WIN55,212-2 during pregnancy altered markers of oxidative stress by significantly reducing oxidative stress and nitrite content. Mitochondrial Complex I and Complex IV activities were also enhanced following prenatal cannabinoid exposure. With regard to apoptosis, pP38 levels were significantly increased, and proapoptotic factor caspase-3 activity, pERK, and pJNK levels were significantly decreased. CB1R and GluA1 levels remained unchanged; however, GluN2A was significantly reduced. There was a significant decrease in MAO activity although tyrosine hydroxylase activity was unaltered. Our study indicates that the effects of prenatal cannabinoid exposure on the cerebellum are unique compared to other brain regions by enhancing mitochondrial function and promoting neuronal survival. Further studies are required to evaluate the mechanisms by which prenatal cannabinoid exposure alters cerebellar processes and the impact of these alterations on behavior.

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“…Spectrophotometric method was used to measure glutathione peroxidase activity in the testis of neonate, juvenile and adult groups using NADPH as a substrate (Ahuja et al, 2017;Majrashi et al, 2018).…”

Section: Glutathione Peroxidase Activitymentioning

confidence: 99%

“…Total monoamine oxidase activity in the testis of neonate, juvenile and adult groups was measured fluorimetrically by determining the amount of 4-hydroxyquinoline formed as a result of kynuramine oxidation (Bhattacharya et al, 2018;Majrashi et al, 2018;Morinan & Garratt, 1985;Muralikrishnan & Mohanakumar, 1998).…”

Section: Monoamine Oxidase (Mao) Activitymentioning

confidence: 99%

Augmented oxidative stress and reduced mitochondrial function in ageing goat testis

Majrashi

Fujihashi

Almaghrabi

et al. 2020

Veterinary Medicine & Sci

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Recently, there is a significant increase in the commercial use of goat products. Nevertheless, there are very few reports on the characterization of redox biomarkers and mitochondrial function in the goat testis. Therefore, in this study we studied the markers of oxidative stress and mitochondrial functions in the goat testis during the process of ageing. Alterations in the markers of oxidative stress/redox biomarkers (contents of reactive oxygen species, nitrite, lipid peroxide, protein carbonyl, glutathione and activities of glutathione peroxidase, monoamine oxidase) and mitochondrial function (Complex‐I and Complex‐IV activities) were elucidated during the process of ageing. Augmented oxidative stress and decreased mitochondrial function were prominent during ageing in the goat testis. Ageing can lead to induction of oxidative stress and decreased production of ATP; however, the prooxidants generated must be effectively removed from the body by the innate antioxidant defence system to minimize the damage to the host tissue. Conversely, the antioxidants cannot completely scavenge the excessive amount of reactive oxygen species produced during ageing or pathological conditions leading to significant cell death and tissue damage. Thus, the use of effective and potent antioxidants in the feed could significantly reduce oxidative stress and improve mitochondrial function, resulting in enriched goat health.

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Dopaminergic neurotoxic effects of 3-TFMPP derivatives

Cited by 16 publications

References 73 publications

Designer drugs: mechanism of action and adverse effects

Designer drugs: mechanism of action and adverse effects

Effects of prenatal synthetic cannabinoid exposure on the cerebellum of adolescent rat offspring

Augmented oxidative stress and reduced mitochondrial function in ageing goat testis

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