Abstract

Chronic renal failure (CRF) consists in a progressive decrease in renal function, and morphological alterations. Current therapies only slow the progression of the disease. Oxidative stress is increased in CRF, and we propose that Boldine, a natural product, antioxidant and inhibitor of connexin hemichannels, could ameliorate the adverse effects associated to oxidative stress in CRF.Rats with CRF (5/6 nephrectomy)were treated with boldine (50mg/kg/day, gavage) for 28 days. Kidney function was evaluated by urinary protein/creatinine (UProt/UCr) and oxidative stress by thiobarbituric acid reactive substances (TBARS). Markers of kidney damage (Col III, ED‐1, FN and α‐SMA) and connexins (Cx) 43 and 37 were evaluated by Western Blot and immunohistochemistry.In CRF+Boldine rats the ratio Uprot/Ucr (4.5±1.3 vs 13.3±4.1, p< 0.05), TBARS (39.5±3.7 vs 62.4 ±1.1 nmol/g, p< 0.05) and the levels of Col III, ED‐1, FN and α‐SMA were lower than in CRF rats. Cx‐43, increased in CRF rats and slightly decreased in CRF + Boldine; on the other hand, CX‐37, was high in control rats and decreased in CRF and CRF + boldine rats to undetectable levels.These results suggest that boldine protects the kidney in rats with chronic renal failure induced by 5/6 nephrectomy, through a mechanism under study, and that in the future, boldine could be used as a nutraceutic for CRF.Funded by Grants Puente VRI 2/2011 and FONDEF D07I1086

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