Infliximab Modulates Cisplatin-Induced Hepatotoxicity in Rats

Cüre, Erkan; Kalkan, Yıldıray; Kırbaş, Aynur; Tümkaya, Levent; Yılmaz, Arif; Turkyilmaz, Aysegul Kucukali; Şehitoğlu, İbrahim; Yüce, Süleyman

doi:10.5152/balkanmedj.2016.150576

Cited by 28 publications

(16 citation statements)

References 34 publications

(35 reference statements)

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“…As the liver hosts receptors belonging to many different varieties of cytokines, it has been widely studied in inflammation models. Reactive oxygen species produced during oxidative stress may further augment Cis's cytotoxic effects in the liver by increasing nuclear kappa factor B expression and release of proinflammatory cytokines (particularly IL-1β, TNF-α, and IL-6) ( 2 , 26 ). We aimed to investigate how proinflammatory cytokines behave in Cis-induced hepatotoxicity and how Dexp affects their tissue levels.…”

Section: Discussionmentioning

confidence: 99%

“…Increased intracellular levels of reactive oxygen species result in DNA injury in the cell nucleus, and when that injury could not be repaired, both proliferation is limited and apoptosis is augmented ( 23 ). Many experimental ischemia reperfusion injury and hepatotoxicity models studied the relationship between antioxidant or free radical scavenging agents and apoptosis by both immunohistochemical staining techniques (active caspase-3, split PARP, TUNEL) and tissue/blood biochemical parameters (IL-6, TNF-α, caspase-3 activity, DNA fragmentation) ( 1 , 2 ). We studied immunohistochemically caspase-3 expression to assess apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Although the duration of Dexp use ranged between 1 and 12 days in the previous experimental studies about the Dexp's cytoprotective effect, we limited that duration to 3 days ( 12 ). The rats in the Cis group were administered a single dose of Cis at a dose of 7 mg/kg only on the first day of the study (Cis 50 mg vials; Kocak Pharma, İstanbul, Turkey) ( 2 , 7 ). The dosage range at which Cis exerts its cytotoxic (hepatotoxic) effects has been shown by the previous experimental studies ( 2 , 7 ).…”

Section: Methodsmentioning

confidence: 99%

“…The rats in the Cis group were administered a single dose of Cis at a dose of 7 mg/kg only on the first day of the study (Cis 50 mg vials; Kocak Pharma, İstanbul, Turkey) ( 2 , 7 ). The dosage range at which Cis exerts its cytotoxic (hepatotoxic) effects has been shown by the previous experimental studies ( 2 , 7 ). The rats in the Cis+Dexp group were administered intraperitoneal Dexp at a dose of 500 mg/kg for three days.…”

Section: Methodsmentioning

confidence: 99%

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Protective effect of dexpanthenol against cisplatin‑induced hepatotoxicity

et al. 2018

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The aim of the present study was to investigate the protective effect of dexpanthenol (Dexp) against cisplatin (Cis)-induced hepatotoxicity. Thirty-two Sprague Dawley rats were divided into four groups: Control group (n=8), Dexp group (n=8, 500 mg/kg/ip/daily single dose/3 days Dexp), Cis group (n=8, 7 mg/kg/ip/single dose Cis) and Cis+Dexp group (n=8, 500 mg/kg/ip/daily single dose/3 days Dexp +7 mg/kg/ip/single dose Cis). MDA, CAT, GSH, GSH-Px, TOS, TAS, OSI, Total Nitrit, IL-1β, IL-6 and TNF-α levels were analyzed in liver tissue samples. After paraffinization of liver tissue samples, histopathological (congestion, loss of glycogen, number of Kupffer cells) and immunohistochemical (caspase-3 expression) parameters were assessed on the paraffinized liver sections. GSH, TAS, TOS, OSI, Tot Nit, L-Arginine, ADMA and SDMA levels were measured in the serum samples. Statistically significant differences were found between the groups in terms of all liver tissue biochemical parameters, with the exception of IL-1β and TNF-α levels. GSH, CAT, GSH-Px, TAS and Tot Nit levels were significantly higher in the Cis+Dexp group compared to the Cis group, whereas MDA, TOS, OSI and IL-6 levels were higher in the Cis group. Similarly, serum GSH, TAS, Tot Nit levels were higher in the Cis+Dexp group whereas TOS, L-Arginine, ADMA and SDMA levels were higher in Cis group. There were statistically significant differences between Control and Cis groups in terms of congestion increase, increase of glycogen loss, increase of Kupffer cell number and increase of caspase-3 expression (P<0.001). There was a statistically significant difference between the Cis and the Cis+Dexp groups in terms of histopathologic parameters, with the exception of congestion (P<0.001). To conclude, histopathological, immunohistochemical, and biochemical results of this study demonstrated that Dexp has a protective effect against Cis-induced hepatotoxicity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Protective effect of dexpanthenol against cisplatin‑induced hepatotoxicity

et al. 2018

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“…Oxidative stress plays an important role in cisplatin-induced hepatotoxicity. Administration of cisplatin especially at higher dose results in hepatotoxicity via formation and activity of reactive oxygen species (ROS) (Cichoż-Lach and Michalak, 2014[ 23 ]; Cüre et al, 2016[ 25 ]). Excessive ROS can stimulate oxidative damage through oxidation of macromolecules such as protein, lipid and DNA.…”

Section: Introductionmentioning

confidence: 99%

Polygonum minus essential oil modulates cisplatin-induced hepatotoxicity through inflammatory and apoptotic pathways

Rashid

Hussan

Hamid

et al. 2020

EXCLI Journal; 19:Doc1246; ISSN 1611-2156

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The beneficial effects of l‐carnitine and infliximab in methotrexate‐induced hepatotoxicity: Emphasis on Notch1/Hes‐1 signaling

Radwan,

Abdel‐Latif,

Abbas

et al. 2023

Archiv der Pharmazie

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Methotrexate (MTX)‐induced hepatotoxicity is a serious adverse effect that may limit its use. Therefore, eligible drugs to ameliorate MTX‐induced hepatotoxicity are required. l‐Carnitine (LC) is a natural molecule with beneficial metabolic effects and infliximab (INF) is an anti‐inflammatory monoclonal antibody against tumor necrosis factor‐alpha (TNF‐α). Recently, Notch1/Hes‐1 signaling was found to play a key role in the pathogenesis of liver injury. However, its role in MTX‐induced hepatotoxicity is unclear. This study aimed to evaluate the modulatory effects of LC or INF on MTX‐induced hepatotoxicity and to explore the underlying mechanism with emphasis on the Notch1/Hes‐1 signaling pathway. Sixty rats were randomized into six groups (n = 10): (1) control (saline); (2) MTX (20 mg/kg MTX, intraperitoneal [ip], once); (3) LC group (500 mg/kg ip, 5 days); (4) INF (7 mg/kg INF ip, once); (5) MTX+LC (20 mg/kg ip, once, 500 mg/kg ip, 5 days, respectively); (6) MTX+INF (20 mg/kg ip, once, 7 mg/kg INF ip, once, respectively). Oxidative stress, inflammatory markers, and Notch1/Hes‐1 were investigated. MTX induced the expression of Notch1 and Hes‐1 proteins and increased the levels of TNF‐α, interleukin (IL)‐6, and IL‐1β in the liver. Cotreatment with LC or INF showed apparent antioxidant and anti‐inflammatory effects. Interestingly, the downregulation of Notch1 and Hes‐1 expression was more prominent in LC cotreatment as compared with INF. In conclusion, LC or INF attenuates MTX‐induced hepatotoxicity through modulation of Notch1/Hes‐1 signaling. The LC ameliorative effect against MTX‐induced hepatotoxicity is significantly better than that of INF. Therefore, LC cotreatment may present a safe and therapeutically effective therapy in alleviating MTX‐induced hepatotoxicity.

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Infliximab Modulates Cisplatin-Induced Hepatotoxicity in Rats

Cited by 28 publications

References 34 publications

Protective effect of dexpanthenol against cisplatin‑induced hepatotoxicity

Protective effect of dexpanthenol against cisplatin‑induced hepatotoxicity

Polygonum minus essential oil modulates cisplatin-induced hepatotoxicity through inflammatory and apoptotic pathways

The beneficial effects of l‐carnitine and infliximab in methotrexate‐induced hepatotoxicity: Emphasis on Notch1/Hes‐1 signaling

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