Insulin-like growth factor and epidermal growth factor treatment: new approaches to protecting steatotic livers against ischemia-reperfusion injury.

Hepatic steatosis is a major risk factor in ischemia-reperfusion (I/R). IGF-binding proteins (IGFBPs) modulate IGF-I action by transporting circulating IGF-I to its sites of action. Epidermal growth factor (EGF) stimulates IGF-I synthesis in vitro. We examined the effect of IGF-I and EGF treatment, separately or in combination, on the vulnerability of steatotic livers to I/R. Our results indicated that I/R impaired IGF-I synthesis only in steatotic livers. Only when a high dose of IGF-I (400 microg/kg) was given to obese animals did they show high circulating IGF-I:IGFBP levels, increased hepatic IGF-I levels, and protection against damage. In lean animals, a dose of 100 microg/kg IGF-I protected nonsteatotic livers. Our results indicated that the combined administration of IGF-I and EGF resulted in hepatic injury parameters in both liver types similar to that obtained by IGF-I and EGF separately. IGF-I increased egf expression in both liver types. The beneficial role of EGF on hepatic I/R injury may be attributable to p38 inhibition in nonsteatotic livers and to PPAR gamma overexpression in steatotic livers. In conclusion, IGF-I and EGF may constitute new pharmacological strategies to reduce the inherent susceptibility of steatotic livers to I/R injury.

[Effect of ischaemic preconditioning and vitamin C on functional recovery of ischaemic kidneys]. / Effet du pré-conditionnement ischémique et de la vitamine C sur la reprise fonctionnelle des reins ischémiques.

OBJECTIVE: To present the results of ischaemic preconditioning (IPC), pharmacological preconditioning with vitamin C (Vit C) and a combination of the two modalities on functional recovery of rat kidneys after prolonged warm ischaemia. MATERIAL: Forty six rats were divided into 5 experimental groups. Kidneys of the sham group (n = 9) were only submitted to dissection of the pedicle. Ischaemia (60 min, n = 10) was induced by clamping both kidneys. IPC (n = 9) consisted of two successive cycles (5 min/5 min) of ischaemia/reperfusion (I/R). Vit C (100 mg/Kg, n = 9) was administered by intravenous injection 30 min before warm ischaemia. The Vit C + IPC (n= 9) group received the combination of both treatments. Tissue malonedialdehyde (MDA), plasma lactate dehydrogenase (LDH), tubular reabsorption of sodium (TRNa) and creatinine clearance (GFR) were evaluated after 120 min of kidney reperfusion. RESULTS: Ischaemic kidneys showed a significant increase of MDA and LDH concentrations and a significant reduction of GFR and TRNa compared to the sham group. The use of lPC or Fit C induced a significant improvement of renal function compared to the ischaemia group. The combination of Vit C + IPC induced a slight improvement of experimental parameters compared to those of the ischaemia group, but did not improve kidney functioning compared to the use of either IPC or Vit C alone. CONCLUSION: IPC and Fit C improve the functional parameters of ischaemic kidneys. However the protective effects are attenuated when the two treatments are combined.