Angiotensin 1-7 and losartan worsen the cisplatin induced nephrotoxicity in female rats

Kasaei, Sayyedehnikta; Pezeshki, Zahra; Karimi, Farzaneh; Lak, Zahra; Choopani, Samira; Talebi, Ardeshir; Nematbakhsh, Mehdi

doi:10.34172/npj.2022.10

Cited by 4 publications

(4 citation statements)

References 12 publications

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“…Other experimental studies on this topic resulted in controversial results: performing experiments with rats, a clear association between AII-AT1R signaling and CDDP nephrotoxicity was observed only in male but not in female animals [ 31 ]. Moreover, in studies with female rats [ 56 ], inhibition of AT1R with Losartan even worsened CDDP-induced nephrotoxicity, probably because of a sex-specific increased renal blood flow induced by AT1R blocking. In rodents, the expression of OCT2 in kidneys appears to be sex-dependent, with higher expression in renal tissue from male animals compared with kidneys from female rats [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Exacerbation of Cisplatin Cellular Toxicity by Regulation of the Human Organic Cation Transporter 2 through Angiotensin II

Kantauskaitè

Hucke

Snieder

et al. 2022

IJMS

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Cisplatin (CDDP) is an efficient chemotherapeutic drug, whose use is associated with the development of serious undesired toxicities, such as nephrotoxicity. The human organic cation transporter 2 (hOCT2), which is highly expressed in the basolateral membrane domain of renal proximal tubules seems to play an important role in the development of CDDP nephrotoxicity. The role of angiotensin II (AII) signaling by binding to the AII receptor type 1 (AT1R) in the development and/or progression of CDDP nephrotoxicity is debated. Therefore, in this work, the regulation of hOCT2 activity by AII and its role in the development of CDDP cellular toxicity was investigated. To do this, hOCT2 was overexpressed by viral transduction in Madin–Darby Canine Kidney (MDCK) cells which were cultivated on a filter. This approach allows the separation of an apical and a basolateral membrane domain, which are easily accessible for experimentation. In this system, hOCT2 was mainly localized on the basolateral plasma membrane domain of the cells. The transporter was functional since a specific uptake of the fluorescent organic cation 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP+) with an affinity (Km) of 35 µM was only detectable by the addition of ASP+ to the basolateral compartment of hOCT2 expressing MDCK (hOCT2-MDCK) cells. Similarly, CDDP toxicity was evident mainly by CDDP addition to the basolateral compartment of hOCT2-MDCK cells cultivated on a filter. The addition of 1 nM AII stimulated hOCT2 function via PKC activation and worsened CDDP cytotoxicity via binding to AT1R. Therefore, the AII signaling pathway may be implicated in the development and/or progression of CDDP nephrotoxicity. This signaling pathway may be a target for protective interventions for example by blocking AT1R in the kidneys. However, it should be further investigated whether these findings obtained in a cell culture system may have translational relevance for the clinical situation. For toxicity experiments, a 100 µM CDDP concentration was used, which is high but allows us to identify clearly toxic effects due to hOCT2. In summary, down-regulation of hOCT2 activity by the inhibition of the AII signaling pathway may protect against CDDP nephrotoxicity.

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Section: Discussionmentioning

confidence: 99%

Exacerbation of Cisplatin Cellular Toxicity by Regulation of the Human Organic Cation Transporter 2 through Angiotensin II

Kantauskaitè

Hucke

Snieder

et al. 2022

IJMS

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“…Te vasodilatory efects of losartan lead to enhance RBF, increase transport of CDDP to the kidneys, and amplify the undesirable efects of CDDP within the kidneys. Tis mechanism can also be attributed to Ang-(1-7) [16]. As Ang-(1-7) reduces renal AT1R expression and increases RBF, so it facilitates CDDP transport to the kidney and may perform more kidney damage [16].…”

Section: Te Pathologic Efects Of Ras On Cddp-inducedmentioning

confidence: 99%

“…Tis mechanism can also be attributed to Ang-(1-7) [16]. As Ang-(1-7) reduces renal AT1R expression and increases RBF, so it facilitates CDDP transport to the kidney and may perform more kidney damage [16]. However, when MasR was blocked by A779 (MasR antagonist), the efect of Ang-(1-7) on CDDP-induced nephrotoxicity did not signifcantly change [16].…”

Section: Te Pathologic Efects Of Ras On Cddp-inducedmentioning

confidence: 99%

The Renin-Angiotensin System Involvement in Cisplatin-Induced Nephrotoxicity: An Overview of Physiological and Pathological Mechanisms—A Systematic Review

Vakilian,

Mohammadi,

Shokri

et al. 2024

International Journal of Nephrology

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Cisplatin (CDDP) is a highly potent chemotherapy drug. But its nephrotoxicity poses a significant limitation to its use. The renin-angiotensin system (RAS) has been proposed to play a role in drug-induced nephrotoxicity. This systematic review (SR) sought to identify the link between CDDP-induced nephrotoxicity and the RAS pathway. In this SR, relevant keywords were employed to explore databases such as PubMed (MEDLINE), Scopus (Elsevier), and Institute for Scientific Information (ISI) Web of Science up to October 2023. Nine studies were selected based on predefined inclusion/exclusion criteria. The findings support the involvement of the RAS in the CDDP-induced nephrotoxicity model, along with the activation of inflammatory mediators, lipid peroxidation, and changes in markers of kidney tissue damage. Furthermore, physiology and pathology of RAS-related interventions in CDDP-induced nephrotoxicity models have involved the factors such as human organic cation transporter 2 (hOCT2), organic anion transporting polypeptides 1B1 (OATP1B1) and 1B3, kallikrein-kinin system, and bradykinin receptors. CDDP-induced nephrotoxicity has been found to be substantially influenced by both classic and nonclassic RAS axes. Angiotensin II exacerbates renal damage induced by CDDP. Conversely, inhibiting the pressor arm of RAS in males mitigates this damage. However, activation of the renal vasodepressor arm of RAS exacerbates CDDP-induced nephrotoxicity in females. These findings underscore gender differences in renal function and response to RAS-related interventions in the presence of CDDP. This SR provides insights into both beneficial and adverse interventions associated with RAS in the CDDP-induced nephrotoxicity, offering valuable considerations for researchers and clinicians.

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“…This precious knowledge conserved by older people is the unique wealth of the area that should be documented for future generations. Therefore, people every year turn to herbal medicine because they believe plant remedies are free from undesirable side effects (George, 2011;Haq, 2004;Kazemipoor, Wan Mohamed Radzi, Cordell, & Yaze, 2012;H. Nasir, 2013).…”

Section: Introductionmentioning

confidence: 99%

An Ethnobotanical Survey of Medicinal Plants Used for Primary Health Care from Patan Sher Khan and Surrounding Areas of District Sudhnoti, Azad Jammu and Kashmir, Pakistan

Liaqat

Hussain

ABID

et al. 2023

joarps

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Life on mountains is difficult and people depend on medicinal plants for primary health care. Many of mountain areas of Azad Kashmir are unexplored from taxonomic and ethnobotanical point of view. This study was conducted to document the indigenous knowledge of medicinal plants of village Patan Sher Khan and allied areas of District Sudhnuti Azad Kashmir Pakistan. Field surveys were conducted during March 2020 to March 2021 for collection of medicinal plants knowledge following standard ethnobotanical methods. A total of 120 key informants were interviewed by using semi-structured questioners. The data were analyzed through ethnobotanical indices i.e., Relative frequency of citation (RFC), Use value (UV), Informant consensus factor (ICF) and Fidelity level (FL). A total of 37 medicinal plant species belonging to 32 genera and 25 families were recorded during the study. Dominant ethnomedicinal families were Fabaceae with 4 species followed by Moraceae and Rosaceae with 3 species each. Leaves were the most frequently used parts (36 %) and decoction was preferred medicinal preparation (19 use reports). Highest relative frequency of citation was recorded for Ficus palmata (0.15) followed by Melia azedarchta (0.14) and highest use value was found for Dodonaea viscosa (0.58). The most valuable plant species of the study area are Ficus carica with 8 use reports and 48 use citations, Bauhinia variegata with 7 use reports and 45 use citations. The maximum value of FL was recorded for Berberis lyceum (100 %) and Plantago lanceolate, (100%). Based on documented data the reported ailments were grouped into 9 categories, The ICF values ranges between 0. 33 (sexual) to 0.90 (teeth and urinary). Medicinal plant knowledge is still alive and large papulation of area still depend on medicinal plants for primary healthcare. But medicinal plant knowledge is declining especially among younger people. Hence, there is an urgent need to document such precious knowledge by continuous ethnobotanical studies.

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Angiotensin 1-7 and losartan worsen the cisplatin induced nephrotoxicity in female rats

Cited by 4 publications

References 12 publications

Exacerbation of Cisplatin Cellular Toxicity by Regulation of the Human Organic Cation Transporter 2 through Angiotensin II

Exacerbation of Cisplatin Cellular Toxicity by Regulation of the Human Organic Cation Transporter 2 through Angiotensin II

The Renin-Angiotensin System Involvement in Cisplatin-Induced Nephrotoxicity: An Overview of Physiological and Pathological Mechanisms—A Systematic Review

An Ethnobotanical Survey of Medicinal Plants Used for Primary Health Care from Patan Sher Khan and Surrounding Areas of District Sudhnoti, Azad Jammu and Kashmir, Pakistan

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