Mouse Models of Acute Kidney Injury

Pabla, Navjotsingh; Scindia, Yogesh; Gigliotti, Joseph C.; Bajwa, Amandeep

doi:10.5772/intechopen.97523

Cited by 1 publication

(3 citation statements)

References 78 publications

(95 reference statements)

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“…Multiple protocols for the induction of renal IR injury have been used to study AKI (reviewed in) 34 , 35 and provide mild (unilateral renal IR), moderate (bilateral renal IR) or severe (unilateral IR with contralateral nephrectomy) pathologies. Variation among mice is highest in the mild and moderate IR models, but improves in the severe IR model.…”

Section: Methodsmentioning

confidence: 99%

“…Variation among mice is highest in the mild and moderate IR models, but improves in the severe IR model. 34 , 35 Therefore, we have used both a moderate and severe IR model in the present studies.…”

Section: Methodsmentioning

confidence: 99%

“…Similarly, IR promoted significant elevation of renal MPO activity (p < 0.01) reflecting granulocyte infiltration into the kidneys, and this was attenuated in IR mice that received opaganib (Figure 2C). However, because of the inherent variability of the moderate IR model, 34,35 these differences between the vehicle-and opaganib-treatment groups did not reach the target level for designation as significant for creatinine (p = 0.12), BUN (p = 0.07) and MPO (p = 0.09).…”

Section: Opaganib Improves Kidney Function and Prevents Mortality Fol...mentioning

confidence: 99%

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The Sphingosine Kinase 2 Inhibitor Opaganib Protects Against Acute Kidney Injury in Mice

Maines¹,

Green²,

Keller³

et al. 2022

IJNRD

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Acute kidney injury (AKI) is a common multifactorial adverse effect of surgery, circulatory obstruction, sepsis or drug/ toxin exposure that often results in morbidity and mortality. Sphingolipid metabolism is a critical regulator of cell survival and pathologic inflammation processes involved in AKI. Opaganib (also known as ABC294640) is a first-in-class experimental drug targeting sphingolipid metabolism that reduces the production and activity of inflammatory cytokines and, therefore, may be effective to prevent and treat AKI. Methods: Murine models of AKI were used to assess the in vivo efficacy of opaganib including ischemia-reperfusion (IR) injury induced by either transient bilateral occlusion of renal blood flow (a moderate model) or nephrectomy followed immediately by occlusion of the contralateral kidney (a severe model) and lipopolysaccharide (LPS)-induced sepsis. Biochemical and histologic assays were used to quantify the effects of oral opaganib treatment on renal damage in these models. Results: Opaganib suppressed the elevations of creatinine and blood urea nitrogen (BUN), as well as granulocyte infiltration into the kidneys, of mice that experienced moderate IR from transient bilateral ligation. Opaganib also markedly decreased these parameters and completely prevented mortality in the severe renal IR model. Additionally, opaganib blunted the elevations of BUN, creatinine and inflammatory cytokines following exposure to LPS. Conclusion:The data support the hypotheses that sphingolipid metabolism is a key mediator of renal inflammatory damage following IR injury and sepsis, and that this can be suppressed by opaganib. Because opaganib has already undergone clinical testing in other diseases , the present studies support conducting clinical trials with this drug with surgical or septic patients at risk for AKI.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Opaganib Improves Kidney Function and Prevents Mortality Fol...mentioning

confidence: 99%

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