Protective effects of silymarin on methotrexate-induced damages in rat testes

Yaman, Turan; Uyar, Ahmet; Kaya, Muhsin; Keleş, Ömer Faruk; Uslu, Barış Atalay; Yener, Zabit

doi:10.1590/s2175-97902018000117529

Cited by 27 publications

(18 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Histological damage to testicle by MTX which includes organization irregularity in the seminiferous tubules, detachment in the germinal epithelium, sloughing germinal epithelial cells in the tubule lumen, vacuolization in the tubules, 12,48,50 interstitial field congestion 51 and oedema 48 has been similarly observed in previous studies. In our study, it was found that normal seminiferous tubules decreased significantly and damaged seminiferous tubules such as detachment, sloughing and vacuolization significantly increased in the MTX group in accordance with some studies in literature.…”

Section: Discussionsupporting

confidence: 77%

Protective effect of pyrrolidine dithiocarbamate against methotrexate-induced testicular damage

2021

Hum Exp Toxicol

View full text Add to dashboard Cite

The aim of the study was to investigate the protective effect of pyrrolidine dithiocarbamate (PDTC) against methotrexate (MTX)-induced testicular damage in rats. Forty Wistar albino male rats were divided into equally four groups: Control group (saline solution, IP), PDTC group (100 mg/kg PDTC,IP, 10 days), MTX group (20 mg/kg MTX, IP, single dose, on the 6th day) and MTX + PDTC group (100 mg/kg PDTC, IP, 10 days and 20 mg/kg MTX, IP, single dose, on the 6th day). After 10 days, testicular tissues were excised for morphometric, histological and immunohistochemical evaluations. Serum testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH) and prokineticin 2 (PK2) levels were determined. Body and testicular weights were measured. Testicular damage was assessed by histological evaluation. Nuclear factor kappa B (NFkB), nuclear factor erythroid 2 related factor 2 (Nrf2) and PK2 immunoreactivities were evaluated by HSCORE. Body and testicular weights, serum FSH, LH, testosterone levels, seminiferous tubule diameter and germinal epithelial thickness were significantly decreased in the MTX group. However, serum PK2 level, histologically damaged seminiferous tubules and interstitial field width were significantly increased. Additionally, there was an increase in NFkB and PK2 immunoreactivity, whereas there was a significant decrease in Nrf2 immunoreactivity. PDTC significantly improved hormonal, morphometric, histological and immunohistochemical findings. Taken together, we conclude that PDTC may reduce MTX-induced testicular damage via NFkB, Nrf2 and PK2 signaling pathways.

show abstract

Section: Discussionsupporting

confidence: 77%

Protective effect of pyrrolidine dithiocarbamate against methotrexate-induced testicular damage

2021

Hum Exp Toxicol

View full text Add to dashboard Cite

show abstract

“…Methotrexate (MTX) is commonly prescribed for the management of malignant tumors [ 1 ] and autoimmune disorders, such as rheumatoid arthritis and psoriasis [ 2 , 3 ]. As a classical folate antagonist, MTX inhibits the dihydrofolate reductase enzyme [ 4 , 5 ]. This results in interruption of DNA replication, ATP synthesis, suppression of cell division, and probable apoptosis [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Methotrexate-Induced Alteration of Renal Aquaporins 1 and 2, Oxidative Stress and Tubular Apoptosis Can Be Attenuated by Omega-3 Fatty Acids Supplementation

El-Agawy

Badawy

Rabei

et al. 2022

IJMS

View full text Add to dashboard Cite

Methotrexate (MTX) is a potent anti-cancer drug, commonly associated with nephrotoxicity via the induction of oxidative stress and apoptosis with alteration of renal water channel proteins, namely aquaporins (AQPs). Omega-3 long-chain polyunsaturated fatty acids (LC-PUFA) have shown cytoprotective effects through their anti-oxidant and antiapoptotic activities. The present study aims for the first time to explore the role of LC-PUFA against MTX-induced nephrotoxicity. Rats were divided into the following groups: saline control, LC-PUFA control, MTX, MTX + LC-PUFA (150 mg/kg), or MTX + LC-PUFA (300 mg/kg). Then, H&E staining and immunohistochemical staining for the anti-apoptosis marker B-cell lymphoma 2 (BCL-2), the apoptosis marker BCL2-Associated X Protein (BAX), the proinflammatory marker Nuclear factor kappa B (NF-kB), AQPs 1 and 2 were performed in kidney sections with an assessment of renal oxidative stress. The MTX caused a renal histopathological alteration, upregulated renal BAX and NF-kB, downregulated Bcl-2 and AQP1, altered the distribution of AQP2, and caused oxidative stress. The LC-PUFA attenuated the pathological changes and decreased renal BAX and NF-kB, increased BCL-2 and AQP1, restored the normal distribution of AQP2, and decreased the oxidative stress. Therefore, LC-PUFA is a good adjuvant to MTX to prevent its adverse effects on kidneys through its antiapoptotic, antioxidant, and anti-inflammatory effect and its role in the restoration of the expression of AQPs 1 and 2.

show abstract

“…On the other hand, treatment with hydroalcoholic extract of chamomile caused a significant increase to normal in AST, ALT, ALP and albumin in CE200 group and CE300 group in response to the increased dose of the extract. This improvement is probably due to the reduction of oxidative stress and the inhibition effect of methotrexate on protein synthesis by the anti-oxidant properties of phenolic compounds present in the plant [3,14,29,30] The results of previous studies also indicate that methotrexate causes total bilirubin to increase as another indicator of hepatotoxicity [5,31,32]. Treatment with chamomile extract caused a significant reduction of bilirubin.…”

Section: Discussionmentioning

confidence: 96%

“…This drug is used at low doses for the treatment of various inflammatory and autoimmune diseases, including rheumatoid arthritis, juvenile idiopathic arthritis and psoriasis, as well as at high doses for treating various types of cancers [2,3]. However, the efficiency of this agent at high doses or long-term therapy is related to its hepatotoxicity and some of the known side effects include hematologic complications, lung and intestinal toxicity [3,4]. The mechanism of liver damage caused by methotrexate has not been clearly specified; nevertheless, it has been reported that methotrexate causes oxidative stress and inflammation in the liver tissue.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Investigation of Protective Effect of Matricaria Chamomilla L. Extract on Methotrexate-Induced Hepatotoxicity in Wistar Rat

Afarani

Mohammadi

Shokri

et al. 2020

Braz. arch. biol. technol.

View full text Add to dashboard Cite

Methotrexate (MTX) was shown to cause oxidative stress and liver damage. The objective was to investigate the possible protective effects of Matricaria Chamomilla L. (chamomile) extract with anti-oxidant and anti-inflammatory properties on the methotrexate-induced liver toxicity. Twenty four Wistar rats were divided into four groups. MTX group was injected intraperitoneally on days 7 and 14 with 20 mg/kg methotrexate. Groups CE200 (chamomile extract 200 mg/kg/day) and CE300 (chamomile extract 300 mg/kg/day) received the same dose of methotrexate added with chamomile extract orally for 15 days at 200 mg/kg and 300 mg/kg respectively and the last group was healthy control group. Results of biochemical analyses indicated serum liver biomarkers (aminotransferases), alkaline phosphatase (ALP), albumin, and liver content of anti-oxidant enzymes (catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)), reduced glutathione (GSH) and total anti-oxidant capacity (TAC) significantly increased (P <0.05-0.001) to normal in the CE treated groups compared to those of the MTX group. Serum bilirubin and hepatic malondialdehyde (MDA) levels significantly increased (P ˂0.001) in MTX group compared to those of the control group and decreased in CE200 and CE300 groups compared to those of the MTX group. Histopathological study showed inflammatory damage, necrotic cells and lipid infiltration in MTX group. In the groups treated with the chamomile extract, a significant improvement was observed in liver tissue in response HIGHLIGHTS  The chamomile extract improved MTX-induced liver histopathological and biochemical changes.  The improvement was significant in the rats that were treated with higher dose of extract (CE300).  The extract enhanced anti-oxidant defense system and decreased MTX-induced oxidative damage. 2 Soltani, M.; et al.

show abstract

Protective effects of silymarin on methotrexate-induced damages in rat testes

Cited by 27 publications

References 30 publications

Protective effect of pyrrolidine dithiocarbamate against methotrexate-induced testicular damage

Protective effect of pyrrolidine dithiocarbamate against methotrexate-induced testicular damage

Methotrexate-Induced Alteration of Renal Aquaporins 1 and 2, Oxidative Stress and Tubular Apoptosis Can Be Attenuated by Omega-3 Fatty Acids Supplementation

Investigation of Protective Effect of Matricaria Chamomilla L. Extract on Methotrexate-Induced Hepatotoxicity in Wistar Rat

Contact Info

Product

Resources

About