Toxicity and postwithdrawal effects of ketamine on the reproductive function of male albino rats: Hormonal, histological, and immunohistochemical study

Paulis, Melad G.; Hafez, E M; El‐Tahawy, Nashwa Fathy Gamal

doi:10.1177/0960327120909857

Cited by 8 publications

(4 citation statements)

References 47 publications

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“…Rats are very often used as the animal experimental model for the assessment of the impact of drugs on the male reproductive system [ 40 – 42 ], bones [ 43 , 44 ], and as well as for the evaluation of direct tissue toxicity [ 45 , 46 ]. Laboratory methods and reagents are available for measurements of hormone levels and immunological studies in rats, ensuring repeatability and facilitating the comparison of results.…”

Section: Introductionmentioning

confidence: 99%

“…The schedule is also personalized due to comorbidities and the risk of drug-drug interactions so the potential for a single agent to cause selective tissue toxicity (not only for drug combinations) may be very important in terms of making clinical decisions [38,39]. Rats are very often used as the animal experimental model for the assessment of the impact of drugs on the male reproductive system [40][41][42], bones [43,44], and as well as for the evaluation of direct tissue toxicity [45,46]. Laboratory methods and reagents are available for measurements of hormone levels and immunological studies in rats, ensuring repeatability and facilitating the comparison of results.…”

Section: Introductionmentioning

confidence: 99%

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Long‐Term Administration of Abacavir and Etravirine Impairs Semen Quality and Alters Redox System and Bone Metabolism in Growing Male Wistar Rats

Matuszewska

Nowak

Niżański

et al. 2021

Oxidative Medicine and Cellular Longevity

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Highly active antiretroviral therapy (HAART) is used in HIV-infected patients. Alongside the prolongation of patients’ life, adverse side effects associated with long-term therapy are becoming an increasing problem. Therefore, optimizing of HAART is extremely important. The study is aimed at evaluating the toxicity of abacavir and etravirine in monotherapy on the reproductive system, liver, kidneys, and bones in young, sexually mature, male rats. Thirty-six 8-week-old male Wistar rats randomized into three 12-animal groups received either normal saline (control), abacavir 60 mg/kg (AB group), or etravirine 40 mg/kg (ET group) once daily for 16 weeks. Semen morphology, oxide–redox state parameters (MDA, SOD, catalase, GPx, glutathione, GSH/GSSG ratio) in tissue homogenates (testes, liver, kidneys), and serum samples were studied. In bones, microcomputed tomography and a four-point bending test were performed. Total sperm count, sperm concentration, motility, and sperm morphology did not differ significantly in AB or ET groups compared to the control. In the flow cytometry of semen, an increased percentage of cells with denatured DNA was noticed for both tested drugs. However, no significant changes of oxide–redox state in testicular homogenates were found, except of increased SOD activity in the AB-receiving group. Additionally, ET significantly altered catalase and GPx in the liver and SOD activity in kidneys. Abacavir decreased catalase in the liver and GSH levels in kidneys. AB caused significant changes to bone microarchitecture (bone volume fraction, trabecular number, connectivity density, total porosity) and increased Young’s modulus. Etravirine had a greater impact on macrometric parameters of bones (tibial index, mid-tibial diameter, femur length). After 4 weeks in the ET group, a lower 1,25-dihydroxyvitamin D3 serum concentration was found. The results showed that abacavir and etravirine disturb oxidative stress. An increase in the percentage of sperms with chromatin damage suggests decreased fertility in rats receiving the studied drugs. Both drugs affected bone formation in growing rats. Additionally, etravirine disturbed vitamin D metabolism.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Long‐Term Administration of Abacavir and Etravirine Impairs Semen Quality and Alters Redox System and Bone Metabolism in Growing Male Wistar Rats

Matuszewska

Nowak

Niżański

et al. 2021

Oxidative Medicine and Cellular Longevity

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show abstract

“…Ketamine has toxic effects on the male reproductive system of humans and animals [15][16][17]. Ketamine exposure in vitro has toxic effects on human sperm functions, including viability, motility, penetration ability, capacitation, and acrosome reaction, and reduces [Ca 2+ ] i [2].…”

Section: Discussionmentioning

confidence: 99%

N-Methyl-d-aspartic Acid (NMDA) Receptor Is Involved in the Inhibitory Effect of Ketamine on Human Sperm Functions

Chen

Yuan

et al. 2021

IJMS

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Ketamine, which used to be widely applied in human and animal medicine as a dissociative anesthetic, has become a popular recreational drug because of its hallucinogenic effect. Our previous study preliminarily proved that ketamine could inhibit human sperm function by affecting intracellular calcium concentration ([Ca2+]i). However, the specific signaling pathway of [Ca2+]i induced by ketamine in human sperm is still not clear yet. Here, the N-methyl-d-aspartic acid (NMDA) receptor was detected in the tail region of human sperm. Its physiological ligand, NMDA (50 μM), could reverse ketamine’s inhibitory effect on human sperm function, and its antagonist, MK801 (100 μM), could restrain the effect of NMDA. The inhibitory effect caused by 4 mM ketamine or 100 μM MK801 on [Ca2+]i, which is a central factor in the regulation of human sperm function, could also be recovered by 50 μM NMDA. The results suggest that the NMDA receptor is probably involved in the inhibitory effect of ketamine on human sperm functions.

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“…Ketamine, also known as K powder, is an N-methyl-D-aspartate receptor antagonist (Paulis et al, 2020). Ketamine was first used as an anesthetic in clinical after it was synthesized in 1962 (Dong et al, 2015;Wang et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Ketamine Induced Bladder Fibrosis Through MTDH/P38 MAPK/EMT Pathway

Zhu

et al. 2022

Front. Pharmacol.

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Purpose: Ketamine is an anesthetic in clinical, but it has also been used as an abusing drug due to its low price and hallucinogenic effects. It is proved that ketamine abusing would cause multiple system damage including the urinary system, which is called ketamine-induced cystitis (KIC). Bladder fibrosis is late stage in KIC and threaten abusers’ life. This study aimed to investigate the molecular mechanism of ketamine-induced bladder fibrosis.Methods: Female Sprague Dawley (SD) rats were randomly divided into 3 groups. 2 groups were treated with tail vein injection of ketamine (25 mg/kg/day, 50 mg/kg/day ketamine hydrochloride solution, respectively) for 12 weeks, whereas the control group was treated with normal saline solution. In each group, rat bladders were extracted and samples were examined for pathological and morphological alterations via hematoxylin and eosin (HE) staining, Masson’s trichrome staining and immunohistochemistry (IHC). SV-HUC-1 cells were treated with different concentrations of ketamine solution (0, 0.1, 0.5, 1 mmol/L). Rat bladder and SV-HUC-1 cells were extracted protein and RNA for Western blot and RT-PCR detection. Metadherin (MTDH) siRNAs and overexpression plasmids were used to knock down and overexpress the relative genes. P38 mitogen-activated protein kinase (MAPK) inhibitor was utilized to inhibit the MAPK pathway.Results: Rats in the ketamine group exhibited fibrosis compared to rats of the control group and fibrosis were also markedly upregulated in SV-HUC-1 cells after treated with ketamine, which were ketamine concentration-dependent. After treating with ketamine in SV-HUC-1 cells, there was an increase expression of MTDH, epithelial-mesenchymal transition (EMT) markers, P38 MAPK. MTDH knockdown would suppresses P38 MAPK/EMT pathway to inhibit fibrosis, however, MTDH overexpression could promote the pathway in SV-HUC-1 cells.Conclusion: In rats and SV-HUC-1 cells ketamine-treated models, MTDH can regulate EMT through the P38 MAPK pathway to regulate the process of bladder fibrosis.

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Toxicity and postwithdrawal effects of ketamine on the reproductive function of male albino rats: Hormonal, histological, and immunohistochemical study

Cited by 8 publications

References 47 publications

Long‐Term Administration of Abacavir and Etravirine Impairs Semen Quality and Alters Redox System and Bone Metabolism in Growing Male Wistar Rats

Long‐Term Administration of Abacavir and Etravirine Impairs Semen Quality and Alters Redox System and Bone Metabolism in Growing Male Wistar Rats

N-Methyl-d-aspartic Acid (NMDA) Receptor Is Involved in the Inhibitory Effect of Ketamine on Human Sperm Functions

Ketamine Induced Bladder Fibrosis Through MTDH/P38 MAPK/EMT Pathway

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