Orally administered microencapsulated lysozyme downregulates serum AGE and reduces the severity of early-stage diabetic nephropathy

Abstract

Diabetic nephropathy is the leading cause of end-stage kidney disease in developed countries and is related to chronic hyperglycaemia. The increased production and tissue deposition of advanced glycation end products (AGE) are known to play a major role in the pathogenesis of diabetic kidney damage. This study was undertaken to determine if lysozyme (LZ), microencapsulated in orally administrable chitosan-coated alginate microspheres (MS), is effective against the early changes seen in the initial stages of diabetic nephropathy. LZ-containing MS (MSLZ) and an equivalent dose (equidose) of nonencapsulated LZ were given as oral treatments. LZ was administered to Wistar rats for seven weeks after diabetes induction with streptozotocin. The results showed that microencapsulated LZ treatment significantly reduced the concentration of serum AGE in the circulation and their deposition in the kidneys. Likewise, MSLZ significantly prevented the development of microalbuminuria compared with untreated diabetic rats. Furthermore, MSLZ significantly prevented the development of glomerular and renal hypertrophy as well as overexpression of AGE receptors (RAGE). An equidose of free LZ had little or no effect whatsoever. Our study supports a relationship between serum AGE and nephropathy in diabetes, and suggests that orally administered microencapsulated LZ can exert kidney-protective activity in a diabetic animal model.