Neurobehavioral, testicular and erectile impairments of chronic ketamine administration: Pathogenesis and ameliorating effect of N-acetyl cysteine

Shehaby, Doaa M. El; El‐Mahdy, Reham I; Ahmed, Abdel Ghaffar M.; Hosny, Ahmed; el‐Rady, Nessren M. Abd

doi:10.1016/j.reprotox.2020.05.016

Cited by 9 publications

(8 citation statements)

References 46 publications

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“…The antioxidant effect can be related to at least three different mechanisms A direct antioxidant effect: NAC can act as a direct antioxidant or direct scavenger for many oxidant radicals such as “NO 2 , ˙OH, and CO 3 ” and non-radical oxidants such as hypochlorous (HOCl) and related species which are oxidants formed from activated neutrophils and monocytes through the activity of myeloperoxidase (MPO) that are involved in the pathophysiology of some lung diseases [ 61 ]. An indirect antioxidant effect : as a result of NAC's capability to act as a cysteine precursor, in which it serves as a substrate for the synthesis of glutathione (GSH) in the body, thus preventing the damaging effects in some organs like; liver, skin, lung, and brain [ 62 ]. GSH is a direct antioxidant for a lot of antioxidant enzymes including glutathione (reductase, peroxidase, glyoxalases 1 and 2, peroxiredoxin, transferase) and (membrane-associated proteins in eicosanoid and glutathione metabolism) MAPEG [ 63 ] .…”

Section: Discussionmentioning

confidence: 99%

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The emerging therapeutic role of some pharmacological antidotes in management of COVID-19

et al. 2022

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Background A novel RNA coronavirus was identified in January 2020 as the cause of a pneumonia epidemic affecting the city of Wuhan; it rapidly spread across China. Aim of the review The aim is to discuss the potential efficacy of some pharmacologically known pharmacological antidotes (N-acetylcysteine; hyperbaric oxygen; deferoxamine; low-dose naloxone) for the management of COVID-19-associated symptoms and complications. Method An extensive search was accomplished in Medline, Embase, Scopus, Web of Science, and Central databases until the end of April, 2021. Four independent researchers completed the screening, and finally, the associated studies were involved. Conclusion The current proof hinders the experts for suggesting the proper pharmacological lines of treatment of COVID-19. Organizations, for example, WHO, should pursue more practical actions and design well-planned clinical trials so that their results may be used in the treatment of future outbreaks.

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Section: Discussionmentioning

confidence: 99%

“…An indirect antioxidant effect : as a result of NAC's capability to act as a cysteine precursor, in which it serves as a substrate for the synthesis of glutathione (GSH) in the body, thus preventing the damaging effects in some organs like; liver, skin, lung, and brain [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

The emerging therapeutic role of some pharmacological antidotes in management of COVID-19

et al. 2022

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“…Ketamine is an antagonist at N-methyl-D-aspartate receptors, glutamate receptors that are mainly expressed in the hippocampus and prefrontal cortex. In a study, ketamine induced the increase of stress oxidative markers such as malondialdehyde (MDA), catalase (CAT), and reduced the total antioxidant capacity (TAC) in rats, proposing that the erectile and testicular dysfunction would be through oxidative stress and decreasing the serum testosterone and luteinizing hormones [ 23 ]. Other study revealed that ketamine at 100 mg/kg/day in rats induced erectly disfunction activating apoptosis by up-regulating of inducible nitric oxide synthase (iNOS) leading to the loss of corporal smooth muscle content and reducing of neuronal nitric oxide synthase (nNOS) expression on cavernous nerve [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Phytochemical Screening by LC-ESI-MS/MS and Effect of the Ethyl Acetate Fraction from Leaves and Stems of Jatropha macrantha Müll Arg. on Ketamine-Induced Erectile Dysfunction in Rats

et al. 2021

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Jatropha macrantha Müll Arg. L is also known as “huanarpo macho” and used in the Peruvian traditional medicine as an aphrodisiac and erectile dysfunction (ED). The aim of this study was to determine the phytochemical constituents in leaves and stems ethyl acetate fraction (LEAF and SEAF) of J. macrantha and to compare the antioxidant activity and the ameliorative effect on ketamine-induced erectile dysfunction in rats. The phytochemical constituents were determined by LC-ESI-MS/MS, the total phenolic compounds and total flavonoids (TPC and TF) by Folin-Ciocalteu and aluminum chloride, respectively. The antioxidant activity was determined by DPPH, ABTS, and FRAP assays. Experimental groups were divided as follows: I: negative control; II: positive control (ketamine at 50 mg/ kg/d); III: sildenafil 5 mg/kg; IV, V, VI: LEAF at 25, 50 and 100 mg/kg, respectively, and VII, VIII, IX: SEAF at 25, 50, and 100 mg/kg, respectively. The phytochemical analysis revealed the presence mainly of coumarins, flavonoids, phenolic acids, and terpenes. TPC of LEAF and SEAF were 359 ± 5.21 mg GAE/g and 306 ± 1.93 mg GAE/g, respectively; TF in LEAF and SEAF were 23.7 ± 0.80 mg EQ/g, and 101 ± 1.42 mg EQ/g, respectively. The DPPH, ABTS, FRAP in SEAF were 647 ± 3.27; 668 ± 2.30; and 575 ± 2.86 μmol TE/g, respectively, whilst LEAF showed 796 ± 3.15; 679 ± 0.85; and 806 ± 3.42 μmol TE/g, respectively. Regarding sexual behavior, LEAF showed a better effect in mount frequency, intromission frequency, ejaculation frequency, mount latency, intromission latency, ejaculatory latency, and post ejaculatory latency than SEAF. As conclusion, LEAF of J. macrantha at 50 mg/kg showed a better effect on sexual behavior in male rats with erectile dysfunction than SEAF but not higher than sildenafil.

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“…In this line, the repeated injection of KET in rodents tested in this model induces deterioration of RM together with various neurophysiological changes. For instance, a significant increase in oxidative stress throughout the brain (Ben-Azu et al , 2018) and in key structures such as PFC and Hp (El Shehaby et al , 2020). Furthermore, repeated administration of this agent produces changes in neuronal cytoarchitecture.…”

Section: Ket-induced Memory Deficit In the Novel Object Recognition Testmentioning

confidence: 99%

Ketamine as a pharmacological tool for the preclinical study of memory deficit in schizophrenia

Santiago

Roldán

Picazo

2022

Behavioural Pharmacology

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Schizophrenia is a serious neuropsychiatric disorder characterized by the presence of positive symptoms (hallucinations, delusions, and disorganization of thought and language), negative symptoms (abulia, alogia, and affective flattening), and cognitive impairment (attention deficit, impaired declarative memory, and deficits in social cognition). Dopaminergic hyperactivity seems to explain the positive symptoms, but it does not completely clarify the appearance of negative and cognitive clinical manifestations. Preclinical data have demonstrated that acute and subchronic treatment with NMDA receptor antagonists such as ketamine (KET) represents a useful model that resembles the schizophrenia symptomatology, including cognitive impairment. This latter has been explained as a hypofunction of NMDA receptors located on the GABA parvalbumin-positive interneurons (near to the cortical pyramidal cells), thus generating an imbalance between the inhibitory and excitatory activity in the corticomesolimbic circuits. The use of behavioral models to explore alterations in different domains of memory is vital to learn more about the neurobiological changes that underlie schizophrenia. Thus, to better understand the neurophysiological mechanisms involved in cognitive impairment related to schizophrenia, the purpose of this review is to analyze the most recent findings regarding the effect of KET administration on these processes.

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Neurobehavioral, testicular and erectile impairments of chronic ketamine administration: Pathogenesis and ameliorating effect of N-acetyl cysteine

Cited by 9 publications

References 46 publications

The emerging therapeutic role of some pharmacological antidotes in management of COVID-19

The emerging therapeutic role of some pharmacological antidotes in management of COVID-19

Phytochemical Screening by LC-ESI-MS/MS and Effect of the Ethyl Acetate Fraction from Leaves and Stems of Jatropha macrantha Müll Arg. on Ketamine-Induced Erectile Dysfunction in Rats

Ketamine as a pharmacological tool for the preclinical study of memory deficit in schizophrenia

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