Resveratrol Protects Against Methotrexate-Induced Hepatic Injury in Rats

Tunalı-Akbay, Tuğba; Şehirli, Özer; Ercan, Feríha; Şener, Göksel

doi:10.18433/j30k5q

Cited by 86 publications

(59 citation statements)

References 36 publications

(37 reference statements)

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“…Thus, manipulation of Bcl-2 family proteins through resveratrol might contribute to the life or death decision for cells under oxidative stress. Interestingly, in contrast to experiments from cancer cell lines, resveratrol was able to protect hepatic tissue [39][40][41]. Consistent with these in vivo studies, we found that resveratrol treatment decreased hepatic cellular apoptotsis in the BDL model.…”

Section: Discussionsupporting

confidence: 87%

The effect of the red wine polyphenol resveratrol on a rat model of biliary obstructed cholestasis: involvement of anti-apoptotic signalling, mitochondrial biogenesis and the induction of autophagy

Lin

Huang

et al. 2012

Apoptosis

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Mitochondria are known to be involved in cholestatic liver injury. The potential protective effect of resveratrol in cholestatic liver injury and the possible roles of autophagy and apoptosis induction in this process are not yet clear. The aim of this study is to determine whether resveratrol administration after bile duct ligation can reduce cholestasis-induced liver injury through modulating apoptosis, mitochondrial biogenesis and autophagy. A rat model of cholestasis was established by bile duct ligation (BDL) and compared with a sham group receiving laparotomy without BDL, with resveratrol or control treatments following BDL. The expression of proteins involved in the apoptotic and autophagic pathways were analyzed by western blotting. Apoptosis was examined by TUNEL staining. In the resveratrol/BDL group LC3-II upregulation persisted for 1-7 days, Bax was downregulated and catalase was upregulated at 3-7 days after resveratrol treatment. The decline in mitochondrial DNA copy number was reversed at 3-7 days. Caspase 3 expression was significantly downregulated at 3-7 days in the resveratrol group. TUNEL staining showed significant numbers of apoptotic liver cells appeared in livers 3-7 days after BDL and that was decreased by resveratrol treatment. Our results indicate that early resveratrol treatment reverses impaired liver function within hours of BDL.

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Section: Discussionsupporting

confidence: 87%

The effect of the red wine polyphenol resveratrol on a rat model of biliary obstructed cholestasis: involvement of anti-apoptotic signalling, mitochondrial biogenesis and the induction of autophagy

Lin

Huang

et al. 2012

Apoptosis

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“…Lyc, a powerful anti-oxidant, has been showed to be effective in reducing the nephrotoxicity caused by cisplatin, via decreasing oxidative stress (4,(38)(39)(40). Lyc's also has anti-infl ammatory and anti-cancer properties.The studies showed that it may be effective in reducing organ toxicity such as pancreas, testis and kidney (39,(41)(42)(43).…”

Section: Discussionmentioning

confidence: 99%

The effects of lycopene on methotrexate-induced liver injury in rats

Yucel¹,

Oğuz²,

Koçarslan³

et al. 2017

BLL

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BACKGROUND: The aim of this study was to investigate the effects of lycopene (Lyc) on methotrexate (Mtx) induced liver toxicity in rats. METHODS: Twenty-eight male Sprague-Dawley rats were divided into four equal groups: control, Lyc, Mtx and Mtx-L: Control group: Rats were given only the vehicle. Lyc group: Rats were given Lyc (10 mg/kg) with corn oil by oral gavage for ten days. Mtx group: Rats were injected intraperitoneally with a single dose of 20 mg/kg of Mtx and given corn oil by oral gavage. Mtx-L group: Rats were post-treated with Lyc (10 mg/kg) for ten days after a single dose of Mtx (20 mg/kg). RESULTS: Mtx administration increased histopathological damage, TNF-α, IL-1β, TOS, TAS and OSI levels in tissues; AST, ALT levels in the blood. Sinusoidal dilatation, infl ammatory cell infi ltration and congestion were signifi cantly improved in the Mtx-L aon histopathologic examination of the rats. In Mtx-L group that were treated at the Lyc, TNF-α and IL-1β levels of liver tissue were decreased signifi cantly compared to Mtx group whereas the decrease in OSI was not signifi cant. Lyc treatment improved the AST and ALT values in Mtx-L group. But only AST improvement was signifi cant. CONCLUSIONS: The results of this study revealed that Lyc might be useful in protecting the liver from injury due to Mtx in rats by reducing the increased proinfl ammatory cytokine levels (Tab. 4, Fig. 1, Ref. 44). Text in PDF www.elis.sk.

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“…Previously, many studies have shown that high-dose MTX treatment can induce increased oxidative stress, resulting in renal and liver damage (3,35–37). However, the specific reactive oxygen species (ROS) induced by MTX treatment have not been identified.…”

Section: Introductionmentioning

confidence: 99%

Vitamin C enhances anticancer activity in methotrexate-treated Hep3B hepatocellular carcinoma cells

et al. 2014

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Methotrexate (MTX) has been widely used for rheumatoid arthritis therapy for a long time. MTX is also used as an anticancer drug for various tumors. However, many studies have shown that high-dose MTX treatment for cancer therapy may cause liver and renal damage. Alhough the mechanisms involved in MTX-induced liver and renal damage require further research, many studies have indicated that MTX-induced cytotoxicity is associated with increases in oxidative stress and caspase activation. In order to reduce MTX-induced side-effects and increase anticancer efficiency, currently, combination treatments of low-dose MTX and other anticancer drugs are considered and applied for various tumor treatments. The present study showed that MTX induces increases in H2O2 levels and caspase-9/-3 activation leading to cell death in hepatocellular carcinoma Hep3B cells. Importantly, this study is the first to demonstrate that vitamin C can efficiently aid low-dose MTX in inducing cell death in Hep3B cells. Therefore, the present study provides a possible powerful therapeutic method for tumors using a combined treatment of vitamin C and low-dose MTX.

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Resveratrol Protects Against Methotrexate-Induced Hepatic Injury in Rats

Cited by 86 publications

References 36 publications

The effect of the red wine polyphenol resveratrol on a rat model of biliary obstructed cholestasis: involvement of anti-apoptotic signalling, mitochondrial biogenesis and the induction of autophagy

The effect of the red wine polyphenol resveratrol on a rat model of biliary obstructed cholestasis: involvement of anti-apoptotic signalling, mitochondrial biogenesis and the induction of autophagy

The effects of lycopene on methotrexate-induced liver injury in rats

Vitamin C enhances anticancer activity in methotrexate-treated Hep3B hepatocellular carcinoma cells

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