Acacia hydaspica R. Parker ethyl-acetate extract abrogates cisplatin-induced nephrotoxicity by targeting ROS and inflammatory cytokines

Abstract Cisplatin (CisPT) is a chemotherapeutic drug that outcomes in adverse effects. In this study, we examined the effect of A. hydaspica ethyl acetate extract (AHE) in an animal model of cisplatin-induced acute kidney injury (AKI). 36 male Sprague Dawley rats were used in the AKI rat model, and...

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Autores principales:	Tayyaba Afsar, Suhail Razak, Dara Aldisi, Maria Shabbir, Ali Almajwal, Abdulaziz Abdullah Al Kheraif, Mohammed Arshad
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/88edb87d317e48a9a3827ddda39a20b0
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spelling	oai:doaj.org-article:88edb87d317e48a9a3827ddda39a20b02021-12-02T19:02:32ZAcacia hydaspica R. Parker ethyl-acetate extract abrogates cisplatin-induced nephrotoxicity by targeting ROS and inflammatory cytokines10.1038/s41598-021-96509-y2045-2322https://doaj.org/article/88edb87d317e48a9a3827ddda39a20b02021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96509-yhttps://doaj.org/toc/2045-2322Abstract Cisplatin (CisPT) is a chemotherapeutic drug that outcomes in adverse effects. In this study, we examined the effect of A. hydaspica ethyl acetate extract (AHE) in an animal model of cisplatin-induced acute kidney injury (AKI). 36 male Sprague Dawley rats were used in the AKI rat model, and CisPT (7.5 mg/kg BW, i.p) single dose was given. In the pretreatment module, AHE (400 mg/kgBW/day, p.o) was given for 7 days before and after CisPT injection. While in the post-treatment group AHE was administered for 7 days after a single CisPT shot. The standard group received silymarin (100 mg/kg BW, p.o) for 7 days before and after CisPT injection. In HCT 116 tumor xenografts (n = 32) two groups of mice were pretreated with 400 mg/kg AHE orally for 7 days and two groups were treated with distilled water. On day 7 of pretreatment one distilled water and one AHE pretreated group were injected i.p with 15 mg/kg bw dose followed by another dose of CisPT 2 wk later. AHE groups were additionally treated with 400 mg/kg AHE for 3 days/week for 2 weeks. CisPT significantly deteriorated renal function parameters, i.e., PH, specific gravity, total protein, albumin, urea, creatinine, uric acid, globulin and blood urea nitrogen. CisPT treatment increased oxidative stress markers, while lower renal antioxidant enzymes. AHE pretreatment ameliorates significantly (p < 0.0001) CisPT-induced alterations in serum and urine markers for kidney function. Furthermore, AHE pretreatment more efficiently (p < 0.001) decreases oxidative stress markers, attenuate NF-κB, and IL-6 protein and mRNA expression by augmenting antioxidant enzyme levels compared to post-treatment. The histological observations verified the protective effect of AHE. In tumor xenograft mice, AHE treatment significantly reduced CisPT induced oxidative stress while it did not interfere with the anticancer efficacy of cisplatin as shown by significance (p < 0.001) decrease in tumor size after treatment. A. hydaspica AHE might provide a prospective adjuvant that precludes CisPT-induced nephrotoxicity without compromising its antitumor potential.Tayyaba AfsarSuhail RazakDara AldisiMaria ShabbirAli AlmajwalAbdulaziz Abdullah Al KheraifMohammed ArshadNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tayyaba Afsar Suhail Razak Dara Aldisi Maria Shabbir Ali Almajwal Abdulaziz Abdullah Al Kheraif Mohammed Arshad Acacia hydaspica R. Parker ethyl-acetate extract abrogates cisplatin-induced nephrotoxicity by targeting ROS and inflammatory cytokines
description	Abstract Cisplatin (CisPT) is a chemotherapeutic drug that outcomes in adverse effects. In this study, we examined the effect of A. hydaspica ethyl acetate extract (AHE) in an animal model of cisplatin-induced acute kidney injury (AKI). 36 male Sprague Dawley rats were used in the AKI rat model, and CisPT (7.5 mg/kg BW, i.p) single dose was given. In the pretreatment module, AHE (400 mg/kgBW/day, p.o) was given for 7 days before and after CisPT injection. While in the post-treatment group AHE was administered for 7 days after a single CisPT shot. The standard group received silymarin (100 mg/kg BW, p.o) for 7 days before and after CisPT injection. In HCT 116 tumor xenografts (n = 32) two groups of mice were pretreated with 400 mg/kg AHE orally for 7 days and two groups were treated with distilled water. On day 7 of pretreatment one distilled water and one AHE pretreated group were injected i.p with 15 mg/kg bw dose followed by another dose of CisPT 2 wk later. AHE groups were additionally treated with 400 mg/kg AHE for 3 days/week for 2 weeks. CisPT significantly deteriorated renal function parameters, i.e., PH, specific gravity, total protein, albumin, urea, creatinine, uric acid, globulin and blood urea nitrogen. CisPT treatment increased oxidative stress markers, while lower renal antioxidant enzymes. AHE pretreatment ameliorates significantly (p < 0.0001) CisPT-induced alterations in serum and urine markers for kidney function. Furthermore, AHE pretreatment more efficiently (p < 0.001) decreases oxidative stress markers, attenuate NF-κB, and IL-6 protein and mRNA expression by augmenting antioxidant enzyme levels compared to post-treatment. The histological observations verified the protective effect of AHE. In tumor xenograft mice, AHE treatment significantly reduced CisPT induced oxidative stress while it did not interfere with the anticancer efficacy of cisplatin as shown by significance (p < 0.001) decrease in tumor size after treatment. A. hydaspica AHE might provide a prospective adjuvant that precludes CisPT-induced nephrotoxicity without compromising its antitumor potential.
format	article
author	Tayyaba Afsar Suhail Razak Dara Aldisi Maria Shabbir Ali Almajwal Abdulaziz Abdullah Al Kheraif Mohammed Arshad
author_facet	Tayyaba Afsar Suhail Razak Dara Aldisi Maria Shabbir Ali Almajwal Abdulaziz Abdullah Al Kheraif Mohammed Arshad
author_sort	Tayyaba Afsar
title	Acacia hydaspica R. Parker ethyl-acetate extract abrogates cisplatin-induced nephrotoxicity by targeting ROS and inflammatory cytokines
title_short	Acacia hydaspica R. Parker ethyl-acetate extract abrogates cisplatin-induced nephrotoxicity by targeting ROS and inflammatory cytokines
title_full	Acacia hydaspica R. Parker ethyl-acetate extract abrogates cisplatin-induced nephrotoxicity by targeting ROS and inflammatory cytokines
title_fullStr	Acacia hydaspica R. Parker ethyl-acetate extract abrogates cisplatin-induced nephrotoxicity by targeting ROS and inflammatory cytokines
title_full_unstemmed	Acacia hydaspica R. Parker ethyl-acetate extract abrogates cisplatin-induced nephrotoxicity by targeting ROS and inflammatory cytokines
title_sort	acacia hydaspica r. parker ethyl-acetate extract abrogates cisplatin-induced nephrotoxicity by targeting ros and inflammatory cytokines
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/88edb87d317e48a9a3827ddda39a20b0
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Acacia hydaspica R. Parker ethyl-acetate extract abrogates cisplatin-induced nephrotoxicity by targeting ROS and inflammatory cytokines

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