Zinc abrogates anticancer drug tamoxifen-induced hepatotoxicity by suppressing redox imbalance, NO/iNOS/NF-ĸB signaling, and caspase-3-dependent apoptosis in female rats

Famurewa, Ademola C.; Ekeleme-Egedigwe, Chima A.; David, Ebuka E.; Eleazu, Chinedum; Folawiyo, Abiola M; Obasi, Nwogo Ajuka

doi:10.1080/15376516.2019.1669243

Cited by 24 publications

(15 citation statements)

References 46 publications

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“…In rats that received CIS only, it was observed that the testicular levels of inflammatory cytokines (IL‐1β, IL‐6 and TNF‐α), NO, and the mechanistic expressions of iNOS and NF‐κB were prominently elevated compared to normal control values (Figures 3 and 4). However, in consistent with our findings, a careful study of the existing literature reveals that other anticancer agents, including methotrexate, doxorubicin, tamoxifen, cyclophosphamide and 5‐fluorouracil, also induce oxidative stress and inflammation as underlying mechanisms of toxicity (Ekeleme‐Egedigwe et al., 2019; El‐Sheikh, Morsy, Abdalla, Hamouda, & Alhaider, 2015; Famurewa et al., 2019, 2020; Negrette‐Guzmán, 2019). In the studies cited above, inflammatory induction is linked to oxidative stress as our study here also suggests.…”

Section: Discussionsupporting

confidence: 89%

“…In rats that received CIS only, it was observed that the testicular levels of inflammatory cytokines (IL-1β, IL-6 and TNFα), NO, and the mechanistic expressions of iNOS and NF-κB were prominently elevated compared to normal control values (Figures 3 and 4). However, in consistent with our findings, a careful study El-Sheikh, Morsy, Abdalla, Hamouda, & Alhaider, 2015;Famurewa et al, 2019Famurewa et al, , 2020Negrette-Guzmán, 2019). In the studies cited above, inflammatory induction is linked to oxidative stress as our study here also suggests.…”

Section: F I G U R Esupporting

confidence: 93%

“…The increased testicular level of NO suggests nitrosative stress shown by elevated total nitrite/nitrate represented by NO level, confirmed by upregulation of iNOS expression in the testis. NO reacts with superoxide anions to initiate oxidation and nitration of GSH, lipids, proteins and DNA to form peroxynitrite radical, which may cause more testicular damage (Famurewa et al., 2020; Kaygusuzoglu et al., 2018). Conversely, the ginger juice considerably prevented CIS induction of oxidative stress‐mediated pro‐inflammatory mechanism in the testis.…”

Section: Discussionmentioning

confidence: 99%

“…and TNF-α (Kaygusuzoglu et al, 2018;Reuter et al, 2010). peroxynitrite radical, which may cause more testicular damage (Famurewa et al, 2020;Kaygusuzoglu et al, 2018). Conversely, the ginger juice considerably prevented CIS induction of oxidative stress-mediated pro-inflammatory mechanism in the testis.…”

Section: F I G U R Ementioning

confidence: 99%

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Ginger juice prevents cisplatin‐induced oxidative stress, endocrine imbalance and NO/iNOS/NF‐κB signalling via modulating testicular redox‐inflammatory mechanism in rats

Famurewa¹,

Ekeleme‐Egedigwe²,

Onwe

et al. 2020

Andrologia

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Chemotherapy is a cornerstone option in cancer treatment owing to its efficacy and effect on quality of life of cancer patients. The action mechanism of anticancer agents is targeted at deregulating cell cycle machinery and inhibiting unscheduled proliferation of cancer cells (Lin et al., 2020). Unfortunately, chemotherapeutic anticancer drugs often exert deleterious effect on healthy cells and tissues leading to systemic toxicity (Negrette-Guzmán, 2019). The toxicity may become unbearable that the treatment regimen has to be disrupted, even when achieving tumoricidal efficacy (Lin et al., 2020). Cisplatin (CIS) is an efficacious anticancer agent; it is the first choice for the treatment of advanced nonsmall-cell lung cancer cells, breast cancer and ovarian cancer (Browning et al., 2017; Lin et al., 2020; Manohar & Leung, 2018). It is of significant value also in the treatment of germ cell and testicular cancers (Thurston, 2007). It unleashes its anticancer action through formation of cisplatin-DNA adduct by intrastrand cross-links due to interaction with cancer cell DNA purine bases eventually leading to p53 activation, cell cycle arrest and induction

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Section: Discussionsupporting

confidence: 89%

Section: F I G U R Esupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: F I G U R Ementioning

confidence: 99%

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Ginger juice prevents cisplatin‐induced oxidative stress, endocrine imbalance and NO/iNOS/NF‐κB signalling via modulating testicular redox‐inflammatory mechanism in rats

Famurewa¹,

Ekeleme‐Egedigwe²,

Onwe

et al. 2020

Andrologia

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“…The crosstalk of oxidative stress and inflammatory response is well known in diabetes. Activation of NF‐κB promotes oxidative stress to signal secretion of cellular pro‐inflammatory cytokines 32,45 . In this study, the kidney and testis levels of pro‐inflammatory cytokines, TNF‐α, IL‐6 and IL‐1β, significantly increased compared to STZ‐DC group.…”

Section: Discussionmentioning

confidence: 49%

Tiliacora triandra extract and its major constituent attenuates diabetic kidney and testicular impairment by modulating redox imbalance and pro‐inflammatory responses in rats

Song

Sun²,

et al. 2020

J Sci Food Agric

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BACKGROUND Literature has demonstrated that diabetes is associated with renal complication and testicular dysfunctions. The current study explored the potential of Tiliacora triandra extract and its major component against diabetic kidney and testicular damages in rats. METHODS Diabetes was induced by high fat diet/streptozotocin (HFD/STZ) and treated orally with Tiliacora triandra extract (TTE, 100 and 400 mg kg−1 body weight) and its major component, 5,7‐dihydroxy‐6‐oxoheptadecanoic acid (DHA, 25 mg kg−1 body weight) for 30 consecutive days. Testicular activities of testicular enzymes, serum levels of testosterone, luteinizing hormone (LH) and follicle‐stimulating hormone (FSH), sperm parameters and urinalysis for protein and albumin levels were evaluated. Renal and testicular biomarkers of oxidative stress and pro‐inflammation were analysed along with histology. RESULTS The experimental diabetes induced significant alterations in the levels and activities of indices evaluated compared to non‐diabetic normal rats. The 28‐day treatment of diabetic rats with TTE and DHA markedly improved activities of testicular enzymes, restored levels of testosterone, LH and FSH and sperm parameters compared to untreated diabetic rats. TTE and DHA abrogated proteinuria and reversed urine albumin level. Testicular and renal oxidative stress and pro‐inflammation were attenuated in diabetic rats treated with TTE and DHA. The diabetes‐mediated histopathological damage was alleviated in the kidney and testis. CONCLUSION The protective effect of TTE and DHA against diabetes induced kidney and testicular damages may be related to its antioxidant and anti‐inflammatory activities. © 2020 Society of Chemical Industry

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Investigating the tamoxifen/high-fat diet synergy: a promising paradigm for nonalcoholic steatohepatitis induction in a rat model

Ezz-Eldin,

Ewees,

Azouz

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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Non-alcoholic steatohepatitis (NASH) is a severe liver condition characterized by excessive fat deposition, ballooning, and lobular inflammation. This investigation was conducted to estimate the capability of concomitant tamoxifen administration (TAM) with a high fat diet (HFD) to induce a reliable NASH model that mimics human NASH features. Rats were administered TAM (25 mg/kg/day p.o.) and consumed HFD for 5 weeks. A time-course investigation was conducted to determine the optimal time for NASH development. Liver function indices, hepatic lipid profile factors, oxidative stress biomarkers, and inflammatory mediators were estimated. Additionally, macroscopic and microscopic changes were examined. Compared with the time-matched control group receiving vehicle alone, TAM/HFD significantly impaired liver function indices represented as marked elevation in ALT, AST, and ALP serum levels. TAM/HFD significantly increased lipid profile factors including high TG and TC hepatic levels. Additionally, TAM/HFD remarkably raised hepatic levels of TNF-α and IL-17 and significantly decreased IL-10. The combination also increases the oxidative status evidenced by high content of MDA as well as low activity of GPx and SOD. Accordingly, the combination of TAM and HFD for 5 weeks collaboratively promotes NASH development by initiating compromised hepatocyte functionality, elevated lipid levels, oxidative stress, and liver inflammation. Graphical abstract

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Zinc abrogates anticancer drug tamoxifen-induced hepatotoxicity by suppressing redox imbalance, NO/iNOS/NF-ĸB signaling, and caspase-3-dependent apoptosis in female rats

Cited by 24 publications

References 46 publications

Ginger juice prevents cisplatin‐induced oxidative stress, endocrine imbalance and NO/iNOS/NF‐κB signalling via modulating testicular redox‐inflammatory mechanism in rats

Ginger juice prevents cisplatin‐induced oxidative stress, endocrine imbalance and NO/iNOS/NF‐κB signalling via modulating testicular redox‐inflammatory mechanism in rats

Tiliacora triandra extract and its major constituent attenuates diabetic kidney and testicular impairment by modulating redox imbalance and pro‐inflammatory responses in rats

Investigating the tamoxifen/high-fat diet synergy: a promising paradigm for nonalcoholic steatohepatitis induction in a rat model

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