Protective effects of febuxostat against paraquat-induced lung toxicity in rats: Impact on RAGE/PI3K/Akt pathway and downstream inflammatory cascades

Ahmed, Maha A.E.; Morsy, Engy M. El; Ahmed, Ashraf M.

doi:10.1016/j.lfs.2019.02.007

Cited by 33 publications

(22 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Most of the current studies on paraquat have focused on lung damage caused by high doses. The increased secretion of proinflammatory factors and proinflammatory mediators in lung tissues that are induced by paraquat have also been reported previously (Amirshahrokhi and Khalili, 2016;Ahmed et al, 2019). Paraquat has also been reported to cause oxidative damage and inflammation in the liver (Amirshahrokhi and Bohlooli, 2013).…”

Section: Discussionsupporting

confidence: 67%

Kaempferol Protects Blood Vessels From Damage Induced by Oxidative Stress and Inflammation in Association With the Nrf2/HO-1 Signaling Pathway

et al. 2020

View full text Add to dashboard Cite

Over recent years, an increasing number of studies have confirmed that the occurrence and development of vascular pathological changes are closely related to oxidative stress and the inflammatory response of the vascular endothelium. Kaempferol is the most common flavonoid compound found in fruits and vegetables. Our present research identified that kaempferol had the capability to protect the vascular endothelium in a mouse model of vascular injury and explored the specific mechanisms underlying these effects by investigating oxidative stress, the extent of cardiovascular injury, and inflammatory markers such as NF-kB, TNF-a, IL-6, and the Nrf2/HO-1 signaling pathway. Analysis showed that kaempferol reduced oxidative stress and inflammation mediated by H 2 O 2 and paraquat, respectively, both in vitro and in vivo. Furthermore, kaempferol suppressed the levels of TNF-a and IL-6, and the activation of NF-kB, in aortic tissues and human umbilical vein endothelial cells (HUVECs). Finally, we observed that kaempferol corrected the levels of antioxidants and elevated the protein levels of Nrf2 and HO-1 in aortic tissues and HUVECs. Collectively, our findings prove that kaempferol protects blood vessels from damage induced by oxidative stress and inflammation and that the Nrf2/HO-1 signaling pathway plays a key role in mediating these effects.

show abstract

Section: Discussionsupporting

confidence: 67%

Kaempferol Protects Blood Vessels From Damage Induced by Oxidative Stress and Inflammation in Association With the Nrf2/HO-1 Signaling Pathway

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Beside decreasing serum uric acid in gout by FBX, there are well documents that FBX suppresses pro-inflammatory cytokines such as IL-1β, IL-6 MCP-1 and TNF-α as well as inhibits the oxidative stress and inflammatory responses through NF-κB pathway in animal models [12,14,62,63]. FBX is able to improve lung damage induced by toxic agents through down-regulation of oxidative stress pathway and suppression of inflammatory mediators [10,18,64]. In addition, FBX ameliorates histopathological changes in lung tissue [65].…”

Section: Discussionmentioning

confidence: 99%

“…FBX by inhibiting oxidation, reduces the inflammation stress [8]. Several studies have already demonstrated the anti-inflammatory [9], anti-oxidant [10] and anti-apoptosis effects of FBX [11]. Several preclinical studies showed that FBX therapy can remarkably inhibit inflammatory responses through reducing the levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 as well as decreasing the nuclear factor kappa B (NF-κB) as a key regulator of inflammation [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

“…Several preclinical studies showed that FBX therapy can remarkably inhibit inflammatory responses through reducing the levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 as well as decreasing the nuclear factor kappa B (NF-κB) as a key regulator of inflammation [12][13][14]. Several studies have shown FBX markedly protects animal against toxic-induced lung inflammation through downstream inflammatory mediators and oxidative stress [15][16][17]. FBX markedly accelerates pulmonary endothelial barrier recovery and improves survival in lipopolysaccharide-induced murine sepsis [18].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Febuxostat as an alternative therapy in COVID-19: A double-blind randomized clinical trial

Davoodi

Abedi

Salehifar

et al. 2020

Preprint

View full text Add to dashboard Cite

Aims: The aim of this double-blind randomized clinical trial was to determine the effects of FBX in comparison with hydroxychloroquine (HCQ) on clinical symptoms, laboratory tests and chest CT findings in patients with COVID-19-causing moderate symptomatic disease. Methods: We conducted a randomized, double blind clinical trial involving adult outpatients' patients with COVID-19 infection, which causes the moderate respiratory illness. Sixty patients were randomly assigned to receive either FBX or HCQ for 5 days. The measured variables were clinical and laboratory data including rate of fever, cough, berating rate, C-Reactive Protein level, lymphocytes count at onset of admission and was well as at 5 days of treatments. In addition, CT lesions were evaluated on admission and 14 days of treatments in both groups. Results: Fever, cough and tachypnea significantly mitigated in both groups after five days of treatments. The lymphocytes count significantly increased in both treatment groups and the CRP values were dropped in normal range (negative) in major of patients receiving FBX or HCQ treatment. It was not observed any significantly difference between FBX and HCQ in frequency of these symptoms. The mean percentages of CT abnormality scores were significantly reduced to 7.3% and 8% after 14 days of FBX and HCQ treatments, respectively. In adult outpatients with moderate symptomatic Covid-19, the effectiveness of FBX was same to HCQ in improvement of clinical manifestations, laboratory tests and CT lesions. Conclusion: These findings suggest FBX as an alternative treatment for Covid-19 infection in patients with contraindication or precaution to HCQ.

show abstract

“…В исследовании M. Ahmed и соавт. [42] применение фебуксостата оказывало защитное действие в отношении оксидативного стресса, вызванного паракватом в ткани легких крыс, что продемонстрировало новые эффекты иКСО.…”

Section: повреждение легких индуцированное паракватомunclassified

Some opportunities of using xanthine oxidase inhibitors

Желябина¹,

Елисеев²

2019

Sovremennaâ revmatologiâ

View full text Add to dashboard Cite

В обзоре представлены современные взгляды на роль фермента ксантиноксидазы (КСО) в патогенезе ряда заболеваний. Показано, что активность ксантиноксидазы (КСО) может быть связана с развитием и прогрессированием не только подагры, но, возможно, и сахарного диабета, артериальной гипертензии и другой сердечно-сосудистой патологии. Парадигма связи гиперурикемии (ГУ) с сердечно-сосудистыми заболеваниями и хроническими заболеваниями почек претерпела ряд изменений -от скептицизма до получения доказательств их серьезного негативного влияния. При этом установлено, что КСО является ключевым ферментом, участвующим в синтезе МК в качестве конечного метаболита адениннуклеотидов и широко представлена в разных органах (печень, кишечник, легкие, почки, сердце и мозг) в плазме крови. КСО играет значимую роль в синтезе не только МК, но и свободных радикалов супероксидов. Существует два возможных механизма, связывающих метаболизм и воспаление, в которых участвует МК: воспаление, активированное кристаллизацией МК, и генерация свободных радикалов супероксидов при ее синтезе. Роль активных форм кислорода обсуждается при ряде патологических состояний: индукция апоптоза/некроза, подавление экспрессии многих генов, активация клеточных сигнальных каскадов, окислительное повреждение ДНК и липидов, воспаление, метаболические расстройства, атеросклероз и др. Ингибирование этих механизмов приводит к снижению синтеза и отложения МК в костно-суставных и других тканях. Соответственно, КСО является подтвержденной мишенью для лечения подагры и, возможно, других состояний, связанных с ГУ. После появления в практике нового ингибитора КСО (иКСО), достижение целевого уровня МК стало реальным более чем у 80% пациентов с подагрой. Потому растет интерес к оценке возможностей иКСО при разных патологических состояниях. Ключевые слова: ксантиноксидаза; активные формы кислорода; ингибиторы ксантиноксидазы; ксантиндегидрогеназа; ксантиноксиредуктаза; гиперурикемия. Контакты: Ольга Владимировна Желябина; olga-sheliabina@mail.ru Для ссылки: Желябина ОВ, Елисеев МС. Некоторые потенциальные возможности применения ингибиторов ксантиноксидазы. Современная ревматология. 2019;13(1):114-120. Some opportunities of using xanthine oxidase inhibitorsZhelyabina O.V., Eliseev M.S. V.A. The review presents modern concepts of the role of xanthine oxidase (XO) in the pathogenesis of a number of diseases. It has been shown that XO activity can be associated with the development and progression not only of gout, but, possibly, diabetes mellitus, hypertension, and other cardiovascular diseases.The paradigm of an association of hyperuricemia (HU) with cardiovascular and chronic renal diseases has undergone certain changes -from skepticism to obtaining the evidence of its serious negative impact. Moreover, XO has been established to be a key enzyme involved in the synthesis of uric acid (UA) as a final adenine nucleotides metabolite, and is extensively present in various organs (the liver, intestine, lung, kidneys, heart, and brain) and in plasma. XO plays an important role in the ...

show abstract

Protective effects of febuxostat against paraquat-induced lung toxicity in rats: Impact on RAGE/PI3K/Akt pathway and downstream inflammatory cascades

Cited by 33 publications

References 59 publications

Kaempferol Protects Blood Vessels From Damage Induced by Oxidative Stress and Inflammation in Association With the Nrf2/HO-1 Signaling Pathway

Kaempferol Protects Blood Vessels From Damage Induced by Oxidative Stress and Inflammation in Association With the Nrf2/HO-1 Signaling Pathway

Febuxostat as an alternative therapy in COVID-19: A double-blind randomized clinical trial

Some opportunities of using xanthine oxidase inhibitors

Contact Info

Product

Resources

About