Chemoprotective Effect of Elettaria Cardamomum against Chemically induced Hepatocellular Carcinoma in Rats by Inhibiting NF-κB, Oxidative Stress, and Activity of Ornithine Decarboxylase

Elguindy, Nihal M.; Yacout, Galila A.; Azab, Eman Fawzy El; Maghraby, Hala K.

doi:10.1016/j.sajb.2016.04.001

Cited by 36 publications

(33 citation statements)

References 52 publications

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“…Interestingly, CAR did not only significantly decrease NFκB levels, it also reduced the NO production in the heart of DOX-intoxicated rats. These data confirm the anti-inflammatory effect of CAR through inhibition of NFκB that was previously reported in rats with chemically induced hepatocellular carcinoma [Elguindy et al, 2016]. Overall, it is likely that the protective effects of CAR against DOX cardiotoxicity are mediated, at least in part, by ROS inhibition, which further prevents the activation of NFκB and the production of its downstream proinflammatory cytokines, thereby reducing tissue damage.…”

Section: Discussionsupporting

confidence: 90%

“…This antioxidant activity of CAR was attributed mainly to its contents of 1,8-cineole, protocatechualdehyde, α-terpineol, and protocatechuic acid [Elguindy et al, 2016]. This antioxidant effect is not restricted to the heart or DOX toxicity as CAR can also suppress lipid peroxidation and increase antioxidant enzyme activities in gentamicininduced nephrotoxicity in rats [Elkomy et al, 2015] and in the liver of obese rats [Elguindy et al, 2016]. CAR treatment before and during DOX led to a significant reduction in serum levels of cardiac damage markers (LDH, CK, and cTnT) compared to treatment with DOX alone.…”

Section: Discussionmentioning

confidence: 99%

“…In agreement, Qiblawi et al [2015] also reported an antioxidant effect for CAR through free radical scavenging, thereby protecting body organs from oxidative damage. This antioxidant activity of CAR was attributed mainly to its contents of 1,8-cineole, protocatechualdehyde, α-terpineol, and protocatechuic acid [Elguindy et al, 2016]. This antioxidant effect is not restricted to the heart or DOX toxicity as CAR can also suppress lipid peroxidation and increase antioxidant enzyme activities in gentamicininduced nephrotoxicity in rats [Elkomy et al, 2015] and in the liver of obese rats [Elguindy et al, 2016].…”

Section: Discussionmentioning

confidence: 99%

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Ameliorative Effect of Cardamom Aqueous Extract on Doxorubicin-Induced Cardiotoxicity in Rats

Gazia¹,

El-Magd²

2018

Cells Tissues Organs

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This study was conducted to evaluate the potential cardioprotective effect of cardamom (CAR) against myocardial injuries induced by doxorubicin (DOX) in rats through investigation of histological alterations and the associated oxidative stress, apoptosis, inflammation, and angiogenesis. This study included 30 adult male albino rats that were randomized to 3 groups (n = 10/group): group I (control), group II (DOX) rats injected with DOX (2.5 mg/kg body weight [BW] i.p.) every other day for 2 weeks, and group III (CAR+DOX) received CAR extract (200 mg/kg BW) orally for 3 weeks, and 1 week later (starting from the 2nd week) they were injected with DOX (2.5 mg/kg BW i.p.) every other day for 2 weeks. Rats treated with DOX alone exhibited notable myocardial damage (discontinuity and disorganization of cardiac muscle fibers, mononuclear cell infiltration, and apparent increases in collagen fiber deposition) accompanied by loss of function (revealed by elevated serum levels of lactate dehydrogenase, creatine kinase, and cardiac troponin), induction of oxidative stress (indicated by higher levels of nitric oxide and malondialdehyde, and lower levels of superoxide dismutase, catalase, and glutathione peroxidase), apoptosis (evidenced by high caspase 3 activity and immunostaining), and inflammation (marked by high cardiac NFκB level). However, administration of CAR not only ameliorated all deleterious effects of DOX but also induced angiogenesis, as indicated by a significant increase in VEGF immunoreactivity. These data indicate that CAR could relieve DOX-induced cardiotoxicity, at least in part, via reductions in oxidative stress, apoptosis, and inflammation and increased tissue regeneration via induction of angiogenesis. Therefore, CAR could be a promising cytoprotective agent against DOX cardiotoxicity.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Ameliorative Effect of Cardamom Aqueous Extract on Doxorubicin-Induced Cardiotoxicity in Rats

Gazia¹,

El-Magd²

2018

Cells Tissues Organs

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“…These results were in accordance with the previous observations. [56][57][58] This might be because DENA, an electrophilic carcinogen may interact with the large nucleophilic pool of GSH thereby reducing the macromolecules and carcinogen interaction. 59 Also, the reduction in cysteine could provide an explanation for the decrease in GSH caused by CCl 4 .…”

Section: Histopathological Studiesmentioning

confidence: 99%

The protective mechanism of Nigella sativa against diethylnitrosamine‐induced hepatocellular carcinoma through its antioxidant effect and EGFR/ERK1/2 signaling

Shahin

Elguindy

Bary

et al. 2018

Environmental Toxicology

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A wide variety of natural products have powerful chemopreventive effects due to their antioxidant, antimutagenic, and anti-inflammatory activities that enable them to arrest cell proliferation in several cancer models. In the present study, we shed light on the protective mechanism of Nigella sativa extract against diethylnitrosamine (DENA)-induced preneoplastic stage of hepatocellular carcinoma (HCC) in rats. We studied the extract effect on EGFR/ERK1/2 signaling pathway as one of the major signaling pathways controlling cell proliferation during hepatocarcinogenesis as well as the investigation of its antioxidant activity. The study also compared the effects of NSEE to those of (thymoquinone) TQ and silymarin as hepatoprotective substances. Rats received daily doses of NSEE (150, 250, 350 mg/kg BW), a dose per three alternative days/week of TQ (20 mg/kg BW) and a daily dose of silymarin (100 mg/kg BW). The doses were administered orally by gavage for 12 days before DENA and CCl administration, and then the supply of NSEE, TQ or silymarin was continued until the end of the experiment (16 weeks). DENA administration activated EGFR/ERK1/2 signaling and caused a significant increase in P-EGFR and P-ERK1/2 as well as a significant up-regulation of expression of target genes such as PCNA, c-fos and Bcl2, which indicated the increase in cell proliferation. Furthermore, a significant elevation in alpha-fetoprotein (AFP) and hepatic enzymes was observed in DENA-treated rats in addition to a decrease in the antioxidant status. The protection with NSEE, TQ, or silymarin has the potential to inhibit the EGFR/ERK1/2 activation and improve the antioxidant status. Moreover, the action of NSEE against the hepatocarcinogenesis was supported by high antioxidant activity and the histopathological observations of the liver. These data suggest that NSEE has a chemopreventive role in DENA-induced HCC through the inhibition of the EGFR/ERK1/2 signaling pathway and their target genes in addition to its role as an antioxidant.

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“…Some mechanisms for modulating cancer signaling and metabolic pathways with EGCG have been proposed based on numerous studies in cells, such as TNF, PI3K/Akt/mTOR, p53, p38 MAPK, and NF‐κB pathways (Chan, Lee, Wang, Yeh, & Liang, ; Elguindy, Yacout, El Azab, & Maghraby, ; Li et al, ; Rady et al, ; Wang, Wang, Wan, Yang, & Zhang, ). Our previous studies also found that EGCG, as well as EC, ECG, and EGC, may bind to some cancer‐related proteins in TPK‐RAS‐MAPK and NF‐κB signaling pathways when used molecular docking of these bioactive substances (Zheng, Chen, & Lu, ).…”

Section: Introductionmentioning

confidence: 99%

Chemoprevention of elite tea variety CFT‐1 rich in EGCG against chemically induced liver cancer in rats

Liao

Lin

Liu

et al. 2019

Food Science & Nutrition

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Camellia sinensis (L.) O. Kuntze cv. CFT‐1 is an elite tea variety bred by sexual hybridization with a high content of epigallocatechin‐3‐gallate (EGCG) as 134.2 mg/g (which is 2.54‐fold that of the common variety). This study was to evaluate the chemopreventive effects of CFT‐1 green tea infusion (CFT‐1) against N ‐nitrosodiethylamine (NDEA)‐induced hepatocarcinogenesis in rats and its mechanisms. The results showed that CFT‐1 had a superior inhibitory effect in NDEA‐initiated hepatocarcinogenesis compared to that of common tea. CFT‐1 significantly reduced the hepatic nodules incidence, size, and number and prevented the hepatic adenoma or hepatocellular carcinoma (HCC) formation. In particular, CFT‐1‐treated animals had the least incidence of HCC (8.33%) followed by common tea treatment (40.00%) and model control rats (87.50%). CFT‐1 treatment significantly ameliorated abnormal liver function enzymes, reduced serum AFP, CEA, TSGF, and TNF‐α levels, inhibited the dickkopf‐related protein‐1 expression, enhanced antioxidant capacity, suppressed the production of livers 8‐hydroxy‐2′‐deoxyguanosine, and regulated hepatic phase I and II xenobiotic‐metabolizing enzymes. Transcriptomic analysis of liver tissue suggested that compared to common tea, administration of CFT‐1 regulated larger gene sets, which were located in several important pathways of antioxidants, inflammatory network, xenobiotic‐metabolizing enzymes, apoptosis, cell proliferation, and metabolism associated with liver tumorigenesis. We identified some genes as potential molecular targets involved in the prevention of CFT‐1 and found that CFT‐1 inhibited inflammation response, proliferation, and accelerated apoptosis by inhibiting NF‐κB and PI3K/Akt pathway. Thus, EGCG‐rich CFT‐1 green tea might be a potential choice for liver cancer prevention/treatment in the future.

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Chemoprotective Effect of Elettaria Cardamomum against Chemically induced Hepatocellular Carcinoma in Rats by Inhibiting NF-κB, Oxidative Stress, and Activity of Ornithine Decarboxylase

Cited by 36 publications

References 52 publications

Ameliorative Effect of Cardamom Aqueous Extract on Doxorubicin-Induced Cardiotoxicity in Rats

Ameliorative Effect of Cardamom Aqueous Extract on Doxorubicin-Induced Cardiotoxicity in Rats

The protective mechanism of Nigella sativa against diethylnitrosamine‐induced hepatocellular carcinoma through its antioxidant effect and EGFR/ERK1/2 signaling

Chemoprevention of elite tea variety CFT‐1 rich in EGCG against chemically induced liver cancer in rats

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