Background: The induceable Hemeoxygenase-1 (HO-1) is the rate limiting step in the conversion of heme into biliverdin, carbon monoxide (CO) and free iron (Fe2+). Up-regulation of HO-1 might be among the most critical cytoprotective mechanism that are activated during cellular stress e.g. inflammation, hyperthermia and ischemia/reperfusion. The elicitors used are mainly hepatotoxic and consequently not adaptable for clinical use. Some nutraceuticals are inducers of HO-1 and ameliorate kidney ischemia-reperfusion-injury (IRI).

Methods: Different nutraceuticals were tested for their potential in up-regulating HO-1 in mice. In a well-established renal artery clamping model in Lewis-rats weighting 250-300g an IRI was set, parameters for kidney function, HO-1 expression and tissue damage were observed at fixed time points. Nutraceuticals were applied orally 24hrs before ischemia and immediately after reperfusion.

Results: Two of the tested nutraceuticals led to a distinct induction of HO-1 expression. (Resveratrol: 11-fold; Ginsing: 17-fold). In the renal artery clamping model serum creatinine and urea levels after 48h of reperfusion (3,06mg/dl +/- 0,86) were significant higher compared to the sham operated group (0,38mg/dl+/-0,07; p < 0,001). The administration of Resveratrol 10mg/kg bw (48h after reperfusion, creatinine: 0,54mg/dl +/- 0,23; p< 0,001) and Ginsing 30mg/kg bw (48h after reperfusion, serum creatinine: 0,53mg/dl +/- 0,06; p< 0,001) led to a significant amelioration of kidney function, respectively. The competitive antagonist Sn-PP (5mg/kg bw) anticipated this positive effect. Histological analysis and dose dependent drug studies as well as HO-1 expression analysis support the study.

Conclusion: The use of non- toxic nutraceuticals is a promising new possibility for inducing HO-1 and hence extenuating ischemia-reperfusion-injury in rat kidney.

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