Ameliorating effects of agomelatine on testicular and epididymal damage induced by methotrexate in rats

Aslankoç, Rahime; Özmen, Özlem; Elli̇dağ, Hamit Yaşar

doi:10.1002/jbt.22445

Cited by 20 publications

(19 citation statements)

References 35 publications

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“…Testicular injury is a serious adverse effect of MTX therapy, thus the preservation of germinal cells is an essential target during cancer chemotherapy [ 6 , 7 ]. In line with previous reports [ 22 , 23 ], MTX treatment in the current study was associated with a significant decrease in testicular weight, indicative of testicular atrophy.…”

Section: Discussionmentioning

confidence: 99%

“…Oxidative stress, which arises as a result of the imbalance between reactive oxygen species (ROS) and the endogenous antioxidant system, is an important factor in MTX-induced testicular injury [ 6 , 7 , 22 , 25 ]. MTX can increase ROS production by the elevation of homocysteine [ 28 ], reduction of NADPH [ 29 ], and activation of NADPH oxidase [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…Inhibition of dihydrofolate reductase by MTX results in suppression of purine and pyrimidine nucleotide production, and subsequently, inhibition of DNA and RNA synthesis, especially in rapidly dividing malignant cells [ 1 , 2 ]. Unfortunately, the cytotoxic effects of MTX are not limited to malignant cells but can also affect normal cells in different organs [ 3 , 4 , 5 ], including the testis [ 6 , 7 ]. Increased oxidative stress, inflammation, and apoptosis may also account for MTX-induced cellular damage [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

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The Possible Contribution of P-Glycoprotein in the Protective Effect of Paeonol against Methotrexate-Induced Testicular Injury in Rats

et al. 2020

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Paeonol, a phenolic ingredient in the genus Paeonia, possesses antioxidant and anti-inflammatory effects. Methotrexate (MTX) is a commonly used chemotherapeutic agent; however, its germ cell damage is a critical problem. P-glycoprotein (P-gp), an efflux transporter, is a member of the blood–testis barrier. The present study evaluated the protective effect of paeonol on MTX-induced testicular injury in rats with the exploration of its mechanism and the possible contribution of P-gp in such protection. Testicular weight, serum testosterone, and testicular P-gp levels were measured. Testicular oxidant/antioxidant status was evaluated via determining the levels of malondialdehyde, total nitrite, reduced glutathione, and superoxide dismutase activity. The inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and the apoptotic marker caspase 3 were estimated immunohistochemically. Testicular histopathology and spermatogenesis scores were also examined. MTX caused histopathologically evident testicular damage with decreased testicular weight, testosterone level, and spermatogenesis score, as well as significant increases in oxidative, inflammatory, and apoptotic responses. Paeonol significantly restored testicular weight, testosterone level, spermatogenesis score, and oxidant/antioxidant balance. Moreover, paeonol increased the testicular P-gp level and significantly decreased TNF-α and caspase 3 immunostaining. In conclusion, paeonol offered a protective effect against MTX-induced testicular injury through its antioxidant, anti-inflammatory, and antiapoptotic effects, as well as by increasing testicular P-gp level.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Possible Contribution of P-Glycoprotein in the Protective Effect of Paeonol against Methotrexate-Induced Testicular Injury in Rats

et al. 2020

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“…[20] For example, the signs of cardiovascular impairment such as arterial hypotension, arrhythmia, and conduction disorder occur instantly, while symptoms like obesity, anemia, or metabolic disorders associated with glucose can only be detected with an n-week delay. [21,22] The long-term effects are easier to treat compared to the acute ones that emerge immediately after poisoning and progress within the period of 3 to 5 days. [4,23] The prolonged use of antipsychotics, even in doses that do not cause poisoning, results in low blood pressure, due to the effect on the autonomic nervous system.…”

Section: Discussionmentioning

confidence: 99%

Retracted: The systemic inflammatory response syndrome in acute antipsychotic poisoning

Zhang

Qiu

Orlova

2020

J Biochem & Molecular Tox

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The purpose of this study was to investigate the mutual effect of systemic inflammatory response syndrome (SIRS) accompanied with fibrinolysis, endotoxemia, and coagulation in severe cases of antipsychotic poisoning. A total of 199 patients were examined, of which 71 were men and 128 were women. The age of the patients was from 22 to 63 years, (45.3 ± 6.1 years on average). According to the results of the course of therapy, the patients were divided into two groups. In the blood plasma, the content of C-reactive protein, fibrinogen and its proteolysis products (oligopeptides, D-dimers), interleukin-6 were determined. In the first 1 to 3 days, in group 1, the level of interleukin-6 decreased and approached the normal level (P ≤ .05). The opposite trend continued throughout the observation of patients from group 2-their levels of interleukin-6 increased day by day (P ≤ .05). The concentration of D-dimer already in 1 day after admission to intensive care in patients from group 2 exceeded the norm by 14 times (P ≤ .05). The level of D-dimer correlated with the level of oligopeptides in blood plasma upon admission, as well as for

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“…Methotrexate (MTX) is a folic acid antagonist used as a medication through the toxic effects of MTX [6][7][8]. It has been reported that male individuals exposed to MTX exhibit oligozoospermia and structural chromosomal rearrangements [9].…”

Section: Introductionmentioning

confidence: 99%

Protective effects of curcumin against methotrexate-induced testicular damage in rats by suppression of the p38-MAPK and nuclear factor-kappa B pathways

Kilinc

2021

Clin Exp Reprod Med

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Objective: Methotrexate (MTX), is a commonly used chemotherapeutic agent. This study aimed to investigate the possibility that curcumin (CMN) protects against MTX-induced testicular damage by affecting the phospho (p)-p38 mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-kB) signaling pathways. Methods: Male Wistar albino rats were subdivided into three groups. The control group was given an intragastric (ig) administration of dimethyl sulfoxide (DMSO) daily for 14 days, the MTX group was given a single intraperitoneal (ip) dose of MTX (20 mg/kg) on the 11th day, and the MTX+CMN group was given ig CMN (100 mg/kg/day, dissolved in DMSO) for 14 days and a single ip dose of MTX (20 mg/kg) on the 11th day. Results: The animal weights, the seminiferous tubule diameter, and germinal epithelium height significantly decreased in the MTX group compared to the control group. The testes weight and the ratio of the testes to body weight did not change, whereas the number of seminiferous tubules and the interstitial space width increased significantly in the MTX group. The number of phospho-p38 (p-p38) MAPK immunopositive cells and the immunoreactivity of NF-kB also increased in the MTX group compared to the control group. Conclusion: CMN prevented the MTX-induced decreases in the body weight, seminiferous tubule diameter, and the germinal epithelium height, while significantly reducing the number of histologically damaged seminiferous tubules and the interstitial space width changes due to MTX. CMN also reduced the number of p-p38 MAPK immunopositive cells and the NF-kB immunoreactivity.

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Ameliorating effects of agomelatine on testicular and epididymal damage induced by methotrexate in rats

Cited by 20 publications

References 35 publications

The Possible Contribution of P-Glycoprotein in the Protective Effect of Paeonol against Methotrexate-Induced Testicular Injury in Rats

The Possible Contribution of P-Glycoprotein in the Protective Effect of Paeonol against Methotrexate-Induced Testicular Injury in Rats

Retracted: The systemic inflammatory response syndrome in acute antipsychotic poisoning

Protective effects of curcumin against methotrexate-induced testicular damage in rats by suppression of the p38-MAPK and nuclear factor-kappa B pathways

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