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2014 ; 1
(ä): 843-857
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Cytoprotection by omega-3 fatty acids as a therapeutic drug vehicle when combined
with nephrotoxic drugs in an intravenous emulsion: Effects on intraglomerular
mesangial cells
#MMPMID28962296
Bonaterra GA
; Wakenhut F
; Röthlein D
; Wolf M
; Bistrian BR
; Driscoll D
; Kinscherf R
Toxicol Rep
2014[]; 1
(ä): 843-857
PMID28962296
show ga
During therapeutic interventions, blood concentrations of intravenously applied
drugs are higher, and their onset of pharmacological action is faster than with
other routes of drug administration. However, acute drug therapy often produces
nephrotoxic side effects, as commonly seen after treatment with Ketorolac or
Gentamicin leading to questions about their use, especially for patients at risk
for acute renal failure. Omega-6(n-6) and omega-3(n-3) polyunsaturated fatty
acids (PUFA) affect eicosanoid metabolism, which plays a role in the regulation
of inflammation. Eicosanoids derived from n-6 FA have proinflammatory and
immunoactive functions, whereas eicosanoids derived from n-3 PUFA have
anti-inflammatory and cytoprotective properties. We hypothesized that providing
such injectable drugs with nephrotoxic potential in combination with n3-PUFAs
from the outset, might afford rapid cytoprotection of renal cells, given the
recent evidence that intravenously administered n3-PUFAs are rapidly incorporated
into cell membranes. We used intraglomerular mesangial cells (MES13) that are
sensitive to treatment with Ketorolac or Gentamicin instead of proximal tubular
cells which do not respond to Ketorolac. We found a significant inhibition of
Ketorolac (0.25, 0.5, 1 mM) or Gentamicin (2.5, 5 mM) induced cytotoxicity after
pretreatment of MES13 cells with 0.01% of 20%w/v LipOmega-3 Emulsion 9/1,
containing 90:10 wt/wt mixture of fish oil derived triglycerides to medium chain
triglycerides.