Quercetin ameliorates methotrexate-induced renal damage, apoptosis and oxidative stress in rats

Erboğa, Mustafa; Aktaş, Cevat; Erboğa, Zeynep Fidanol; Dönmez, Yeliz Bozdemir; Gürel, Ahmet

doi:10.3109/0886022x.2015.1074521

Cited by 67 publications

(39 citation statements)

References 33 publications

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“…This is because it is a primary effector activated as a result of various death signals and disintegration of significant cellular proteins (Jänicke et al, ). MTX leads to DNA defects by causing apoptosis with inhibition of purine and pyrimidine (Erboga et al, ). Caspase‐dependent apoptotic signaling plays an important role in apoptotic damages induced by MTX (Erboga et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…MTX leads to DNA defects by causing apoptosis with inhibition of purine and pyrimidine (Erboga et al, ). Caspase‐dependent apoptotic signaling plays an important role in apoptotic damages induced by MTX (Erboga et al, ). Similarly, in another study, it was observed that apoptosis increased in kidney tissue after MTX application (Vardi et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…SLY, NRG and all other reagents of analytical grade were obtained from Sigma-Aldrich Chemical Company. The dose of MTX was determined based on a recent study reported by Erboga, Aktas, Erboga, Donmez, and Gurel (2015). SLY and NRG were dissolved in distilled water.…”

Section: Chemicalsmentioning

confidence: 99%

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Therapeutic effects of silymarin and naringin on methotrexate-induced nephrotoxicity in rats: Biochemical evaluation of anti-inflammatory, antiapoptotic, and antiautophagic properties

et al. 2017

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Silymarin (SLY) and naringin (NRG) are natural flavonoids that have been reported to have many benefits and medicinal properties. The present study was designed to investigate the protective effect of SLY and NRG against methotrexate (MTX)‐induced nephrotoxicity in experimental animals. Rats were subjected to oral pretreatment of SLY (25 and 50 mg/kg body weight (b.w.)/day) and NRG (50 and 100 mg/kg b.w./day) for 7 days against renal toxicity induced by single intraperitoneal administration of MTX (20 mg/kg b.w.). MTX resulted in an increase in serum toxicity markers, lipid peroxidation, and reduction in activities of antioxidant enzymes. Additionally, MTX provoked inflammatory responses by increasing the levels of TNF‐α, IL‐1β, IL‐6, NF‐κB, and activation of COX‐2 and iNOS. Furthermore, MTX administration caused apoptosis and autophagy by increasing activity of Caspase‐3 and light chain 3B level. Conversely, SLY and NRG therapy significantly decreased these values in rats. This study demonstrated that SLY and NRG protect against MTX‐induced nephrotoxicity. Practical applications Chemotherapeutic drugs have been used for cancer treatment for many years. However, in the treatment process, they may damage organs such as liver and kidney, prolong the treatment process and negatively affects patient welfare. This study revealed that silymarin and naringin exhibited potent anti‐inflammatory, antiapoptotic, and antiautophagic effect in renal injury caused by methotrexate, a chemotherapeutic drug. Therefore, treatment silymarin and naringin can be used for the beneficial effect against methotrexate‐induced kidney damage in cancer chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Therapeutic effects of silymarin and naringin on methotrexate-induced nephrotoxicity in rats: Biochemical evaluation of anti-inflammatory, antiapoptotic, and antiautophagic properties

et al. 2017

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“…Increasing evidence has indicated that quercetin exerts various biological activities, such as antioxidant, anti-tumor, anti-angiogenesis and anti-inflammatory functions (14,15). Quercetin has also been reported to have a therapeutic effect on renal function and tissue damage (16,17). To the best of our knowledge, the effect of quercetin on kidney fibrosis and whether miRNAs are serving a role in quercetin-induced renal protective effects has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Quercetin is able to alleviate TGF‑β‑induced fibrosis in renal tubular epithelial cells by suppressing miR‑21

Cao

Jianying

et al. 2018

Exp Ther Med

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Patients with chronic kidney disease (CKD) are characterized by a gradual loss of kidney function over time. A number of studies have indicated that tubule interstitial fibrosis (TIF) is associated with the occurrence and development of CKD. The aim of the present study was to investigate the effect of quercetin treatment on the fibrosis of renal tubular epithelial cells and to determine whether the anti-fibrotic effects of quercetin are achieved via microRNA (miR)-21. Human tubular epithelial HK-2 cells were cultured with transforming growth factor (TGF)-β to induce fibrosis and the expression of fibrotic markers collagen I, fibronectin, α-smooth muscle actin (SMA) and epithelial-cadherin were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Cells were treated with 7.5, 15 or 30 mg/ml quercetin, following which fibrosis and miR-21 expression were evaluated. Quercetin-treated cells were transfected with miR-21 mimics and the expression of fibrotic markers was examined using RT-qPCR. Finally, the expression of fibrosis-associated miR-21 target genes, phosphatase and tensin homolog (PTEN) and TIMP Metallopeptidase Inhibitor 3 (TIMP3), was measured in cells treated with quercetin with or without miR-21 mimics using RT-qPCR, western blotting and immunocytochemistry. The results revealed that TGF-β treatment induced a significant increase in the expression of fibrotic markers in HK-2 cells, while quercetin treatment partially inhibited the fibrosis of HK-2 cells. Furthermore, quercetin treatment significantly inhibited TGF-β-induced miR-21 upregulation and transfection with miR-21 mimics reversed the anti-fibrotic effects of quercetin. Quercetin treatment markedly upregulated PTEN and TIMP3 expression, whereas transfection with miR-21 mimics reversed this effect. The results of the present study suggest that quercetin is able to alleviate TGF-β-induced fibrosis in HK-2 cells via suppressing the miR-21 and upregulating PTEN and TIMP3. Quercetin may have potential as an anti-fibrotic treatment for patients with renal fibrosis.

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“…The findings of present study are also similar with those reported by Dabak DO et al [17] which showed dilated Bowman's space, inflammatory cell infiltration, glomerular and peritubular vascular congestion and swelling of renal tubular epithelial cells. Erboga M et al [18] showed prominent degenerative changes with tubular degeneration, tubular dilatation, tubular cell swelling, cellular vacuolization, glomerular congestion and degeneration in the renal cortical tissues. These findings are in accordance with our observations which revealed chronic inflammatory foci with infiltration of cells with congestion and haemorrhage in all the three groups.…”

Section: Discussionmentioning

confidence: 98%

Histopathologcal Effects of Methotrexate on Rat Kidney –An Experimental Study on Wistar Albino Rats.

Balowria¹,

Officer

Syed

et al. 2019

AANAT

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Introduction: Methotrexate, a folic acid antagonist is used as a first line drug for the treatment of a number of malignancies and immune disorders like rheumatoid arthritis. Due to hepatoxicity its dose needs to be monitored and sometimes it has to be stopped. In the present study we intend to do a detailed histopathological investigation after methotrexate toxicity on the relatively neglected organ i.e. kidney of rat. Subjects and Methods: Albino rats were divided into four groups (1, 2, 3, and 4) of six animals each. Control group 1 was given distilled water whereas experimental groups 2, 3, and 4 were given low, therapeutic and high doses of methotrexate orally for 28 days. Results: The results showed congestion and infiltration of the glomeruli and interstitial edema and tubular degeneration which were dose dependent. Conclusion: The degenerative changes necessitate extra precautions to be taken while using drug for prolonged period. The study merits due to great social impact.

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Quercetin ameliorates methotrexate-induced renal damage, apoptosis and oxidative stress in rats

Abstract: In conclusion, renal toxic effects of MTX may be alleviated by QE.

Cited by 67 publications

References 33 publications

Therapeutic effects of silymarin and naringin on methotrexate-induced nephrotoxicity in rats: Biochemical evaluation of anti-inflammatory, antiapoptotic, and antiautophagic properties

Therapeutic effects of silymarin and naringin on methotrexate-induced nephrotoxicity in rats: Biochemical evaluation of anti-inflammatory, antiapoptotic, and antiautophagic properties

Quercetin is able to alleviate TGF‑β‑induced fibrosis in renal tubular epithelial cells by suppressing miR‑21

Histopathologcal Effects of Methotrexate on Rat Kidney –An Experimental Study on Wistar Albino Rats.

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