Mechanisms of Thymoquinone Hepatorenal Protection in Methotrexate-Induced Toxicity in Rats

El-Sheikh, Azza A. K.; Morsy, Mohamed A.; Abdalla, Ahlam M.; Hamouda, Azza Hussien; Alhaider, Ibrahim A.

doi:10.1155/2015/859383

Cited by 112 publications

(105 citation statements)

References 36 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Subsequently, NF-κB binds to DNA and up-regulates the transcription of many inflammatory genes like cytokine, chemokine and receptors of advanced glycation end products [27]. The present study revealed the marked activation of NF-κB pathway (NF-κB, p-IKKα and p-IκBα) upon MTX administration which is in accordance with the previous reports [7,28]. Sitagliptin pretreatment showed marked inhibitory effect on NF-κB activation pathway.…”

Section: Discussionsupporting

confidence: 92%

Hepatoprotective effect of sitagliptin against methotrexate induced liver toxicity

et al. 2017

View full text Add to dashboard Cite

Sitagliptin is selective dipeptidyl peptidase-4 inhibitor (DPP4-I), used clinically as a new oral anti-diabetic agent. This study explored the underlying mechanisms of the hepatoprotective role of sitagliptin pretreatment against methotrexate (MTX) induced hepatotoxicity in mice. Forty mice were divided into four groups (10 mice each); control, MTX, and two sitagliptin groups (pretreated with sitagliptin 10 and 20 mg/kg/day, respectively) for five consecutive days prior to MTX injection. Results showed that MTX induced marked hepatic injury in the form of cloudy swelling, hydropic degeneration, apoptosis and focal necrosis in all hepatic zones. Biochemical analysis revealed significant increase in the serum transaminases, alkaline phosphatase and lactate dehydrogenase in MTX group. Oxidative stress and depressed antioxidant system of the hepatic tissues were evident in MTX group. MTX down-regulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and reduced its binding capacity. Additionally, MTX increased the activation and the expression of nuclear factor kappa-B (NF-κB) and downstream inflammatory mediators. MTX induced the activation of inducible nitric oxide synthase (iNOS) and increased nitrite/nitrate level. Finally, hepatic cellular apoptosis was clearly obvious in MTX-intoxicated animals using TUNEL staining. Also, there was increase in the immunoexpression of pro-apoptotic protein Bax, increase in Bax and caspase-3 levels and decrease in the level of anti-apoptotic Bcl2 in liver. On the other hand, sitagliptin pretreatment significantly ameliorated all of the above mentioned biochemical, histopathological, immunohistochemical changes induced by MTX. These results provide new evidences that the hepatoprotective effect of sitagliptin is possibly mediated through modulation of Nrf2 and NF-κB signaling pathways with subsequent suppression of inflammatory and apoptotic processes.

show abstract

Section: Discussionsupporting

confidence: 92%

Hepatoprotective effect of sitagliptin against methotrexate induced liver toxicity

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The study by El-Sheikh et al [65] indicated that TQ treatment (10 mg/kg) concurrently with MTX in rats restored hepatorenal functions, as well as their normal histology. TQ also reversed oxidative and nitrosative stress, as well as inflammatory and apoptotic signs induced by MTX alone.…”

Section: Resultsmentioning

confidence: 99%

An Overview on Renoprotective Effects of Thymoquinone

et al. 2018

View full text Add to dashboard Cite

Background: Kidneys as vital organs remove waste material from blood. Additionally, they may also have a role in the electrolyte balance, regulation of blood pressure, and red blood cell genesis. Kidney diseases may be caused by several factors such as ischemia/reperfusion injury, diabetes, and nephrotoxic agents. Oxidative stress and inflammation are involved in the pathogenesis and progression of kidney diseases. Traditionally, natural antioxidants are used for treatment of renal failure in various countries. Summary: People usually select natural antioxidants since they have an opinion that herbal medicine has not any important side effects. Nigella sativa is a flavoring herb that is widely used as a condiment and as a remedy for many disorders. Thymoquinone (TQ), the most important component of black seeds, mainly oil, is considered as an active agent responsible for a lot of the seed’s useful effects. This review describes the protective roles and related mechanisms of TQ against renal disorders. The search terms, including TQ, antioxidant, renal ischemia-reperfusion, diabetic nephropathy, and nephrotoxic agent were searched in scientific databases. TQ showed anti-inflammatory and antioxidant properties in animal and in vitro models of several renal diseases caused by inflammation and oxidative stress. Key Messages: Experimental studies have shown beneficial effects of TQ against renal diseases; however, well-designed clinical trials in humans are required to confirm these effects.

show abstract

“…El-Sheikh et al, found imparted levels of oxidative stress parameters, nitroxidative stress and downregulation of TNF-α/ NF-κB/COX-2 inflammatory pathway in methotrexate treated animals and this may contribute in the development of hepatorenal damage. 23 Kalemci et al, also found that increase in liver enzyme levels and increased rate of inflammatory cell infiltration in pulmonary tissue of methotrexate treatment rats. The increased rate of inflammatory cell infiltration in pulmonary tissue may be due to mitogen-activated protein kinase (MAPK) and Akt pathways.…”

mentioning

confidence: 92%

Ameliorative Effect of Quercetin on Methotrexate Induced Toxicity in Sprague-Dawley Rats: A Histopathological Study

David¹,

Satyanarayana²,

Parasuraman³

et al. 2016

IJPER

View full text Add to dashboard Cite

Objective: To study the effect of quercetin on methotrexate induced toxicity and to observe the histopathological changes. Materials and Methods: Thirty male rats were divided into 5 different groups with each group consisting of six rats. The Group I was a control and they were treated with 10 ml/kg of carboxymethyl cellulose. The Group II, III, IV and V animals were treated with methotrexate 0.125 mg/kg; methotrexate 0.25 mg/kg; methotrexate (0.125 mg/kg) + quercetin (500 mg/kg); and methotrexate (0.25 mg/kg) + quercetin (500 mg/kg), respectively. All drugs were administered orally through oral gavage once daily for 14 days. At the end of the study, blood samples were collected from all the animals in each group. The animals were then sacrificed and organs were collected for histopathological analysis. Results: Methotrexate 0.125 and 0.25 mg/kg significantly increased the levels of liver enzymes such as AST, ALT, ALP and total protein and renal markers such as urea and creatinine. The animals treated with quercetin along with methotrexate showed significant improvement on methotrexate induced liver and renal toxicities. Methotrexate significantly reduced the levels of haemoglobin and blood sugar and which was partially reversed by quercetin. The notable histopathological changes in lungs, liver and kidneys were observed with methotrexate treated animals and this was protected by quercetin. Conclusion: Methotrexate produced significant pathological changes at 0.250 mg/kg and possible ameliorative effect of quercetin observed in lung, liver and kidney. Quercetin 500 mg/kg significantly inhibited the methotrexate induced toxicity in liver and kidneys.

show abstract

Mechanisms of Thymoquinone Hepatorenal Protection in Methotrexate-Induced Toxicity in Rats

Cited by 112 publications

References 36 publications

Hepatoprotective effect of sitagliptin against methotrexate induced liver toxicity

Hepatoprotective effect of sitagliptin against methotrexate induced liver toxicity

An Overview on Renoprotective Effects of Thymoquinone

Ameliorative Effect of Quercetin on Methotrexate Induced Toxicity in Sprague-Dawley Rats: A Histopathological Study

Contact Info

Product

Resources

About