Effect of gervital in attenuating hepatotoxicity caused by methotrexate or azathioprine in adult albino rats

Abdul-Hamid, Manal; Abdel-Reheim, Eman S.; Hegazy, Walaa; Allam, Ahmed A.; Othman, Sarah I.; Alwaele, Maha Abdulla; Abdel-Kawi, Samraa Hussein

doi:10.1007/s11356-022-18903-x

Cited by 4 publications

(3 citation statements)

References 46 publications

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“…Elevated oxidative stress coupled with an inflammatory outburst, orchestrated through GSH and xanthine oxidase-mediated reactions, is a pivotal pathological mechanism underlying AZA-provoked hepatocellular toxicity (Menor et al 2004;Schaalan et al 2018;van Liere et al 2021;Abdul-Hamid et al 2022). In our earlier study, it has been demonstrated that oxidative stress-mediated DNA fragmentation is one of the pivotal mechanisms underpinning hepatocyte cell death (Shanmugarajan et al 2008).…”

Section: Discussionmentioning

confidence: 94%

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L-Ergothioneine protects hepatocytes against azathioprine-Induced toxicity via NIK/NF-ΚB signaling axis

Ramachandraboopathi

Sathanantham

2022

ijhs

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This research study has major implications for the development of ESH as a safe and holistic hepatoprotectant and could be used as an adjuvant in the treatment of IBD to minimize DILI. We demonstrate that ESH regulates oxidative stress, NIK/NF-κB-mediated inflammatory axis, and improves the hepatocellular integrity against AZA-provoked deleterious events in the hepatocytes (Figure 5). However, further research is warranted to elucidate the efficacy, specificity, and safety of ESH in AZA-treated patients with normal genetic makeup and gene polymorphisms.

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Section: Discussionmentioning

confidence: 94%

“…is highly beneficial in the alleviation of hepatotoxic manifestations of AZA. (Menor et al 2004;van Liere et al 2021;Abdul-Hamid et al 2022). In stark contrast, a recent report by Madrazo et al (2021) indicated that allopurinol potentially enhances myelotoxicity (manifested as megaloblastic anemia and leukopenia).…”

Section: Introductionmentioning

confidence: 99%

L-Ergothioneine protects hepatocytes against azathioprine-Induced toxicity via NIK/NF-ΚB signaling axis

Ramachandraboopathi

Sathanantham

2022

ijhs

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“…Chemotherapy drugs can cause testicular apoptosis, which is an obviously harmful side effect (Abu-Risha et al 2022). GSE is a powerful antioxidant as demonstrated by previous studies (Abdul-Hamid et al 2022;Priyadarshi et al 2022) which compared the efficacy of GSE and Ginkgo biloba to reduce hepatotoxicity induced by antidysrhythmic drugs.…”

Section: Discussionmentioning

confidence: 95%

Impact of gervital against histopathological, ultrastructural, and biochemical alterations caused by methotrexate or azathioprine in albino rat testis

Abdul-Hamid

Abdel-Reheim

Hegazy

et al. 2022

Environ Sci Pollut Res

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Methotrexate (MTX) and azathioprine (AZA) are chemotherapeutic, immunosuppressive, cytotoxic drugs with reported adverse effects, including oxidative damage to testis. This study aims to evaluate the potential effect of grape seed extract (GSE; gervital) to prevent testicular damage caused by MTX and AZA. Male albino rats were separated into six groups: group I, normal control group; group II, GSE (150 mg/kg/day); group III, MTX (8 mg/kg/week); group IV, AZA (15 mg/kg/day); group V, GSE (150 mg/kg/day) + MTX (8 mg/kg/week); group VI, GSE (150 mg/kg/day) + AZA (15 mg/kg/day). All rats were sacrificed, blood samples were obtained for testosterone analysis, and testis was removed for histological and ultrastructural studies and oxidation measurements. A reduction in relative body and testis weight, along with a significant decrease in testosterone levels, was observed. Histopathological and ultrastructural alterations induced by MTX or AZA included reduced spermatozoa, sloughing, marked reduction of spermatogenic cells, and pyknosis of some nuclei. Significant oxidative stress manifested as reduced glutathione (GSH) levels and catalase (CAT) and superoxide dismutase (SOD) activities, as well as increased malondialdehyde (MDA) levels. GSE administration showed an ameliorative effect on testosterone levels and histopathological and ultrastructural changes. GSE treatment also suppressed the increases in MDA levels and the decreases in GSH levels and CAT and SOD activities. In conclusion, these findings confirm that GSE is an effective antioxidant that protects testis from histopathological and ultrastructural damage induced by MTX and AZA. Therefore, GSE is a promising candidate for future use to minimize and alleviate MTX and AZA risks. Graphical abstract

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Oxidative stress

Boutros¹,

Ray²

2024

Encyclopedia of Toxicology

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Effect of gervital in attenuating hepatotoxicity caused by methotrexate or azathioprine in adult albino rats

Cited by 4 publications

References 46 publications

L-Ergothioneine protects hepatocytes against azathioprine-Induced toxicity via NIK/NF-ΚB signaling axis

L-Ergothioneine protects hepatocytes against azathioprine-Induced toxicity via NIK/NF-ΚB signaling axis

Impact of gervital against histopathological, ultrastructural, and biochemical alterations caused by methotrexate or azathioprine in albino rat testis

Oxidative stress

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