Hypolipidemic effects of fenofibrate in normal and hyperlipidemie animals

Arakawa, Reijiroh; Tsuchiya, Asato; Sakamoto, Yoko; Tanaka, Toshiya; Katayama, K.; Nagayama, Takashi; Saitoh, Kiyoshi

doi:10.1016/s0021-5198(19)47092-3

Cited by 1 publication

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“…The doses of fenofibrate and bezafibrate were determined based on those used in previous studies to treat mice. [20][21][22][23] In addition to BUN and Ccr, the expression levels of Kim-1 and Lcn-2 in the kidneys were measured and evaluated histologically as indicators of renal damage. Cisplatin-induced renal injury is assumed to be caused by proximal tubular cell injury, and just as BUN and Ccr values reflect GFR, Kim-1, and Lcn-2 in the kidneys are considered to be suitable indicators of renal injury.…”

Section: Discussionmentioning

confidence: 99%

“…As fenofibrate was extracted as a candidate drug through big data analysis, we also examined the effect of bezafibrate, a known fibrate drug. The doses of fenofibrate and bezafibrate were determined based on those used in previous studies to treat mice 20–23 . In addition to BUN and Ccr, the expression levels of Kim‐1 and Lcn‐2 in the kidneys were measured and evaluated histologically as indicators of renal damage.…”

Section: Discussionmentioning

confidence: 99%

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Discovery of preventive drugs for cisplatin‐induced acute kidney injury using big data analysis

Kanda

Goda

Maegawa

et al. 2022

Clinical Translational Sci

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Cisplatin is effective against many types of carcinoma. However, a high rate of renal damage is a clinical problem. Thus, there is a need to establish a method to prevent it. Although various compounds have been reported to be effective against cisplatin-induced renal injury, there are no examples of their clinical application. Therefore, we attempted to search for prophylactic agents with a high potential for clinical application. We used Cascade Eye to identify genes that are altered during cisplatin-induced renal injury, Library of Integrated Network-based Cellular Signatures (LINCS) to identify drugs that inhibit changes in gene expression, and a large database of spontaneous adverse drug reaction reports to identify drugs that could prevent cisplatin-induced kidney injury in clinical practice. In total, 10 candidate drugs were identified. Using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), we identified drugs that reduce cisplatin-induced kidney injury.Fenofibrate was selected as a candidate drug to prevent cisplatin-induced kidney injury based on the FAERS analysis. A model was used to evaluate the efficacy of fenofibrate against cisplatin-induced renal injury. Studies using HK2 cells and mouse models showed that fenofibrate significantly inhibited cisplatin-induced renal injury but did not inhibit the antitumor effect of cisplatin. Fenofibrate is a candidate prophylactic drug with high clinical applicability for cisplatin-induced renal injury. Analysis of data from multiple big databases will improve the search for novel prophylactic drugs with high clinical applicability. For the practical application of these findings, evaluation in prospective controlled trials is necessary.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%