A novel effect of Aprepitant: Protection for cisplatin-induced nephrotoxicity and hepatotoxicity

“…In this experimental study, 64 male BALB/c mice (25)(26)(27)(28)(29)(30) 15 The animals were kept under standard laboratory conditions (23 ± 2°C, 55 ± 5% moisture, 12:12 h light/dark cycle) with free access to food and water.…”

Section: Animals and Experimental Designmentioning

confidence: 99%

Alleviation of cisplatin‐induced hepatotoxicity by gliclazide: Involvement of oxidative stress and caspase‐3 activity

Taghizadeh

Hosseinimehr

Zargari

et al. 2021

Pharmacology Res & Perspec

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“…Cisplatin, another chemotherapeutic drug widely used for the treatment of cancer, induces a serious side-effect (nephrotoxicity), in addition to vomiting, bone marrow suppression and hair loss. In experimental animals, it has been demonstrated that NK-1R antagonists (e.g., aprepitant) counteracted the nephrotoxicity and hepatotoxicity mediated by cisplatin [108,122]. Thus, the treatment with cisplatin increased oxidative stress and the levels of tissue cytokines and serum enzymes and induced inflammatory infiltration and necrosis in both the liver and kidney, whereas aprepitant normalized all the parameters studied (e.g., kidney and liver oxidative parameters and inflammatory cytokines).…”

Section: Safetymentioning

confidence: 98%

“…Doxorubicin cardiotoxicity is mediated by the SP/NK-1R system, and it is known that aprepitant decreases cardiotoxicity and increases the sensitivity of tumor cells to doxorubicin (Table 2) [98]. Moreover, in preclinical studies, it has been demonstrated that aprepitant exerts a protective role against the hepatotoxicity and nephrotoxicity induced by the chemotherapeutic drug cisplatin [108] and that aprepitant (2 mg/kg/day for 12 weeks) inhibited the cutaneous (e.g., nose crusting, scabbing, skin reddening and alopecia) and neurogenic inflammation side-effects mediated by erlotinib (an epidermal growth factor receptor-tyrosine kinase inhibitor used as an anticancer treatment) [109]. Erlotinib increases the level of SP, which mediates the side-effects observed, whereas aprepitant mitigates it, including causing a decrease in the number of NK-1Rs expressed in the skin.…”

Section: Relationships Between Aprepitant and Other Drugsmentioning

confidence: 99%

The Neurokinin-1 Receptor Antagonist Aprepitant: An Intelligent Bullet against Cancer?

Muñoz

Coveñas

2020

Cancers

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Neurokinin-1 receptor (NK-1R) antagonists exert antitumor action, are safe and do not cause serious side-effects. These antagonists (via the NK-1R) exert multiple actions against cancer: antiproliferative and anti-Warburg effects and apoptotic, anti-angiogenic and antimetastatic effects. These multiple effects have been shown for a broad spectrum of cancers. The drug aprepitant (an NK-1R antagonist) is currently used in clinical practice as an antiemetic. In in vivo and in vitro studies, aprepitant also showed the aforementioned multiple antitumor actions against many types of cancer. A successful combination therapy (aprepitant and radiotherapy) has recently been reported in a patient suffering from lung carcinoma: the tumor mass disappeared and side-effects were not observed. Aprepitant could be considered as an intelligent bullet against cancer. The administration of aprepitant in cancer patients to prevent recurrence and metastasis after surgical procedures, thrombosis and thromboembolism is discussed, as is the possible link, through the substance P (SP)/NK-1R system, between cancer and depression. Our main aim is to review the multiple antitumor actions exerted by aprepitant, and the use of this drug is suggested in cancer patients. Altogether, the data support the reprofiling of aprepitant for a new therapeutic use as an antitumor agent.

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“…The RNA samples were reverse-transcribed into complementary DNA using a high-capacity cDNA reverse transcription kit (Applied Biosystem). The cDNA concentrations were assessed and quantified using the Epoch Spectrophotometer System and Take3 Plate (Biotek) 27,28 .…”

Section: Total Rna Extraction and Cdna Synthesismentioning

confidence: 99%

Protective effects of phloretin and phloridzin on indomethacin-induced gastric ulcers in mice: characterization of potential molecular mechanisms

Ün

Uğan

2020

Cukurova Medical Journal

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We aimed to examine the potential protective effects of phloretin and phloridzin in indomethacin induced ulcer model in mice. Materials and Methods: In total 54 female Balb/C mice were separated into nine groups. Famotidine was used as standard antiulcer agent. The phloretin and phloridzin was given at the doses of 50 and 100 mg/kg as a pre-treatment. After experimental procedures stomach tissue oxidative parameters (SOD, GSH and MDA), inflammatory cytokine TNF-α, and COX1 and COX2 mRNA expressions were analyzed. In addition, to clarify antiulcer effect mechanism of phloretin and phloridzin, numerical densities of ulcerative areas were analyzed. Results: Phloretin and phloridzin inhibited indomethacininduced ulcer formation in dose dependent manner. Tissue inflammation and oxidative stress were increased after the indomethacin administration. Phloretin and phloridzin treatment normalized all parameters compared to indomethacin treated group. After the treatments, SOD activities and GSH levels were increased while MDA levels were decreased. Phloretin and phloridzin treatments decreased TNF-α, COX1 and COX2 mRNA expressions. Conclusion: Our results showed that phloretin and phloridzin may be an alternative treatment for peptic ulcer disease due to their potential regulatory effects against oxidative stress and inflammation. Amaç: Bu çalışmada farelerde indometazine bağlı ülser modelinde, floretin ve floridzinin potansiyel koruyucu etkilerini incelemeyi amaçlanmıştır. Gereç ve Yöntem: Toplam 54 dişi Balb/C faresi dokuz gruba ayrıldı. Famotidin standart anti-ülser madde olarak kullanıldı. Floretin ve floridzin, tedavi gruplarına 50 ve 100 mg/kg dozlarında verildi. Deneysel prosedürlerden sonra, mide dokusunda oksidatif parametreleri (SOD, GSH ve MDA), enflamatuar sitokin TNF-α ve COX1 ve COX2 mRNA ekspresyonları analiz edildi. Ayrıca, floretin ve floridzinin anti-ülser etki mekanizmasını açıklığa kavuşturmak için ülserli alanların sayısal yoğunlukları analiz edilmiştir. Bulgular: Floretin ve floridzin, indometazine bağlı gelişen ülser oluşumunu doza bağımlı olarak azalttı. İndometazin uygulamasından sonra enflamasyon ve oksidatif stresin arttığı belirlendi. Floretin ve floridzin tedavisi indometazin ile tedavi edilen gruba kıyasla tüm parametreleri normalleştirmiştir. Tedavilerin ardından, indomethazin grubuna kıyasla, SOD aktiviteleri ve GSH düzeyleri yükselirken, MDA düzeyleri azalmıştır. Floretin ve floridzin uygulamarının TNF-α, COX1 ve COX2 mRNA ekspresyonlarını azalttığı tespit edildi. Sonuç: Sonuçlarımız oksidatif stres ve enflamasyona karşı potansiyel düzenleyici etkileri nedeniyle floretin ve floridzinin peptik ülser hastalığı için alternatif bir tedavi olabileceğini göstermiştir.

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A novel effect of Aprepitant: Protection for cisplatin-induced nephrotoxicity and hepatotoxicity

Cited by 53 publications

References 43 publications

Alleviation of cisplatin‐induced hepatotoxicity by gliclazide: Involvement of oxidative stress and caspase‐3 activity

Alleviation of cisplatin‐induced hepatotoxicity by gliclazide: Involvement of oxidative stress and caspase‐3 activity

The Neurokinin-1 Receptor Antagonist Aprepitant: An Intelligent Bullet against Cancer?

Protective effects of phloretin and phloridzin on indomethacin-induced gastric ulcers in mice: characterization of potential molecular mechanisms

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