Reduction of cisplatin ototoxicity in rats by oral administration of pomegranate extract

Yazıcı, Zahide Mine; Meriç, Ayşenur; Mıdı, Ahmet; Arınc, Yasar Volkan; Kahya, Volkan; Hafız, Günter

doi:10.1007/s00405-011-1582-2

Cited by 24 publications

(20 citation statements)

References 32 publications

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“…Some natural antioxidants, such as Vitamin E, Gingko Biloba, pomegranate and resveratrol (Yazici et al 2012;Olgun et al 2014), block the ototoxic effect of cisplatin. The otoprotective effect of resveratrol was observed only in low doses; otherwise, it enhanced the ototoxic impact of cisplatin in higher doses (Olgun et al 2014).…”

Section: Discussionmentioning

confidence: 99%

Protective effect of Pycnogenol on cisplatin-induced ototoxicity in rats

Eryılmaz

Eliyatkın

Demirci

et al. 2016

Pharmaceutical Biology

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Context: PycnogenolV R , which is French maritime pine bark extract, is a potent antioxidant. It is used in medical conditions caused by oxidative stress. Cisplatin (cis-diamminedichloroplatinum II) is an antineoplastic agent. However, its serious side effects such as ototoxicity limit its usage. Objective: Antioxidants can be used to prevent ototoxicity. We investigated the effect of Pycnogenol V R on cisplatin-induced ototoxicity. Materials and methods: Rats were randomly assigned to four groups of five. Distortion product-evoked otoacoustic emissions (DPOAE) test was performed for each rat. The experimental groups were as follows: Control Group, Pycnogenol V R Group: 10 mg/kg Pycnogenol V R intraperitoneally for 7 days, Cisplatin Group: intraperitoneally 15 mg/kg single injection of cisplatin on the fifth day, Cisplatin þ Pycnogenol V R Group: intraperitoneally 10 mg/kg Pycnogenol V R treatment for 7 days, additionally on the fifth day, 15 mg/kg single injection of cisplatin was given. On the eighth day, DPOAE was re-performed and rats were sacrificed. Apoptosis was evaluated histopathologically. Results: Mean percentage of apoptotic cells was 1.5, 3, 30 and 11% in organ of Corti and 2, 2, 40, 15% in spiral ganglion neurons in Control Group, Pycnogenol V R Group, Cisplatin Group and Cisplatin þ Pycnogenol V R Group, respectively. Cisplatin Group and Cisplatin þ Pycnogenol V R Group were significantly different when compared to Control Group histopathologically both in organ of Corti and spiral ganglion neuron (p <0.001, p ¼ 0.019, p ¼ 0.001, p ¼ 0.015). DPOAE results showed that Cisplatin þ Pycnogenol V R Group was significantly different when compared to Cisplatin Group at 3, 6 and 8 kHz (p < 0.05). Conclusion: Pycnogenol protected against cisplatin ototoxicity. Also, pycnogenol is not ototoxic. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Protective effect of Pycnogenol on cisplatin-induced ototoxicity in rats

Eryılmaz

Eliyatkın

Demirci

et al. 2016

Pharmaceutical Biology

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“…Entretanto, o CE 50 da cisplatina (55,87 ±1,10µM) é 4 vezes menor que o CE 50 da morina (220,30 ±1,08µM), sendo portanto, mais ativa (Tabela 01). Pesquisas mostram que a morina possui baixa toxicidade ao organismo, contrapondo-se a cisplatina que apresenta resultados limitados pelos efeitos colaterais como náusea, vômitos e nefrotoxicidade (Yazici et al, 2012;Said & Tsimberidou, 2014). Para o extrato de oliveira, não foi possível calcular o CE 50 por não atingir o limiar de 50%, apresentando efeito na dose de 800 µg/mL para o método de MTT (Figura 02).…”

Section: Determinação Da Viabilidade Da Célula H460 Tratada Com O Comunclassified

Ação antiproliferativado flavonoide morina e do extrato da folha de oliveira (Oleaeuropaea L.) contra a linhagem de célula H460

Pereira¹,

Oliveira²,

Kanashiro³

et al. 2015

Rev. bras. plantas med.

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RESUMO:O presente estudo investigou a indução de morte celular por apoptose pelo flavonóide morina e pelo extrato da folha de oliveira (Oleaeuropaea L.) em linhagens de células de câncer de pulmão do tipo não pequenas (H460). O tratamento com morina e o extrato de oliveira em células H460 resultou na redução do crescimento tumoral e indução de morte celular avaliados pelos ensaios de MTT e lactato desidrogenase (LDH) e a morte celular por apoptose confirmada por microscopia de fluorescência e análise por citometria de fluxo. Os dados indicaram que o flavonóide morina e o extrato de oliveira diminuíram a viabilidade celular para taxas percentuais de 7,22± 1,54% e 62,37± 2,85% nas concentrações de 800µM e µg/mL, respectivamente. As maiores taxas percentuais de morte celular por apoptose foram100% para morina na concentração de 800µM e 70,49 ± 5,91% para o extrato de oliveira na concentração de 800 µg/ mL. Estes resultados foram associados com a alteração do potencial de membrana mitocondrial, cujos valores são de 54,91% para morina na concentração de 400µM e 42,2% para o extrato de oliveira na concentração de 800 µg/mL sugerindo envolvimento da via intrínseca da morte celular por apoptose. Portanto, morina e o extrato de oliveira afetaram a viabilidade celular da linhagem H460 induzindo morte celular por apoptose. Palavras-chave:Linhagens de células H460, morina, extrato de oliveira, atividade antitumoral. ABSTRACT:The antiproliferative action of morin flavonoid and olive leaf extract (Olea europaea L.) against the cell line H460. This study investigates possible apoptosis induction mechanism by the flavonoid morin and the olive leaf extract (Olea europaea L.) in non-small lung cancer cells (H460). The treatment with morin and olive leaves extract resulted in growth inhibition and induction of apoptosis in H460 cells lines measured by the MTT assay methods and confirmed by fluorescence microscopy, flow cytometry analysis. The data indicated that themurin and the extract of olive decreased the cell viability percentage rates of 7.22 ± 1,54% and 62.37 ± 2,85% in the concentrations of 800 µM and µg/mL, respectively. The highest percentage rates of cell death by apoptosis were 100% for themorin in a concentration of 800 µM and 70.49 ± 5.91% for the olive extract in a concentration of 800 µg/mL. These findings were associated with altered mitochondrial membrane potential, whose value is 54.91% for the murin concentration of 400 µM and 42.2% for the olive extract in a concentration of 800 mg / mL, suggesting involvement of the intrinsic pathway of cell death by apoptosis. Therefore, the morin and the olive extract affect the cell viability of H460 cell lines inducing cell death by apoptosis.

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“…A previous study indicated that oral PPE decreases the levels of ROS, as well as acute inflammation in the tympanic membrane following myringotomy (11). Moreover, the oral administration of PPE in rats has been shown to reduce cisplatin-induced toxicity in the cochlea; therefore, an oral experimental dose of PPE may have a powerful effect in protecting cisplatin-induced ototoxicity in rats (12). However, the molecular mechanisms underlying PPE-induced protection from ototoxic drugs are not yet fully understood.…”

Section: Introductionmentioning

confidence: 99%

FoxO3a plays a key role in the protective effects of pomegranate peel extract against amikacin-induced ototoxicity

Liu

Zhang

Sun

et al. 2017

International Journal of Molecular Medicine

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The use of amikacin (AMK) in present treatment strategies results in severe ototoxicity; however, the underlying molecular mechanisms of this toxicity remain unclear. In this study, we investigated the effectiveness of orally administered pomegranate peel extract (PPE), a strong antioxidant, as a protective agent against AMK-induced ototoxicity. To this end, PPE was orally administered to adult BALB/c mice for 5 days, and the mice were then concurrently treated with AMK (500 mg/kg/day for 15 consecutive days). Auditory threshold shifts induced by AMK were significantly attenuated. The results of immunohistochemical staining and western blot analysis revealed that PPE exerted its protective effects by by downregulating the phosphorylation of Forkhead box O3a (FoxO3a), an important transcription factor which is involved in the responses to oxidative stress. The results also showed that PPE treatment inhibited mitogen-activated protein kinase phosphorylation, prevented the activation of pro-apoptotic protein caspase-3, decreased the levels of apoptosis-inducing Bax protein, and increased the levels of the anti-apoptotic mediator, Bcl-2, induced by AMK in the mouse cochlea. Taken together, our experimental findings suggest that phosphorylated FoxO3a mediates AMK-induced apoptosis in BALB/c mice cochlea. PPE effectively attenuated oxidative stress and ototoxicity by regulating FoxO3a, and may thus prove to be beneficial in protecting auditory cells from ototoxic drugs.

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Reduction of cisplatin ototoxicity in rats by oral administration of pomegranate extract

Cited by 24 publications

References 32 publications

Protective effect of Pycnogenol on cisplatin-induced ototoxicity in rats

Protective effect of Pycnogenol on cisplatin-induced ototoxicity in rats

Ação antiproliferativado flavonoide morina e do extrato da folha de oliveira (Oleaeuropaea L.) contra a linhagem de célula H460

FoxO3a plays a key role in the protective effects of pomegranate peel extract against amikacin-induced ototoxicity

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