Background: Renal ischemia reperfusion injury (IRI) contributing to acute kidney injury is an important comorbidity in the context of solid organ transplantation. Here we present a dietary omega-3 poly unsaturated fatty acid (PUFA) food supplementation study to investigate whether pre-treatment can reduce IRI.
Methods: Male 12-14 week old C57BL/6J mice were used for the study. One group received omega-3 food supplementation (2 % in the chow containg 10% fat) and one control group had chow with low omega-3 FA for 2 weeks prior to induction of IRI. Bilateral 30 min renal pedicle clamping was done and mice were sacrificed at 24h after surgery. S-creatinine and BUN elevation were measured. Kidney damage was analyzed by histology, immunohistochemistry for neutrophile infiltration, NGAL and A1M (alpha-1 microglobulin). mRNA expression of pro-inflammatory cytokines (IL-6, MCP1). Fatty acid and oxylipin pattern were quantified in blood and kidney tissue.
Results: The feeding regim massively increased the levels of omga 3-PUFA. Consistently eicosanoids and others oxylipins from omega 3 PUFA were elevated while omega 6 PUFA derived mediators such a proinflammatory prostaglandins were decreased. Omega-3 feeding resulted in attenuation of serum creatinine increase (omega-3: 99 ± 21 µmol/L vs vehicle: 163 ± 5, baseline 18± 1 µmol/L n=7, * p<0.05 ). Similar effects were seen for BUN elevation. PAS stain revealed similar degrees of AKI and tublar NGAL elevation. Howeve, the tubular transport marker A1M was significantly higher expressed in omega-3 compared to vehicle treated mice. This indicates better integrity of proximal tubular epithelial cells. IL-6 and MCP-1 elevation due to IRI in renal tissue was not affected by omega-3 treatment.
Discussion: There are various reports on treatment strategies with omega-3 FA in the context of renal diseases. Here, we showed that omega-3 pre-treatment attenuated worsening of renal function after IRI and that tubular transport was protected as well. However, inflammation was similar in the vehicle treated and the omega-3 treated groups.
Conclusion: Dietary omega-3 food supplementation resulted in benefical effects on renal function impairment in experimental renal IRI in mice but did not attenuate tissue inflammation.