Ultrastructural study of combined therapy effect of Losartan and Octreotide on inhibition of glomerular epithelial changes in uninephrectomized diabetic rats

In diabetes mellitus the increase of AgII (Angiotensin II), IGF-1(insulin like growth factor-1) and growth hormone induce kidney lesions especially changes in content and thickness of GBM and widening and fusion of podocyte pedicles. In this research for the first time the combination of Losartan (AT1 receptor blocker) and Octreotide (Somatostatin analogue) were used in order to prevent glomerular epithelial lesions. In this experimental study 15 male rats (2 months age) were uninephrectomised from left flank and divided in 5 groups (3 per group). 7 days later diabetes was induced in 2th, 3th, 4th and 5th group by Alloxan (120mg/kg) subcutaneously. 5 days after diabetes induction, the third group received Losartan (5mg/kg/day) orally, 4th group Octretide (10 ŭg/day) subcutaneously and 5th group both two drugs with the mentioned doses for 8 weeks. The 2th group was served as diabetic non treatment group. Kidneys of all groups were fixed by perfusion technique. After second fixation of 1 mm3 cortex parts in Osmium Tetroxide, they were processed in TAAB812 resin for embedding. Thin sections (600 nm thickness) were prepared and investigated by transmission electron microscope qualitatively. Losartan inhibited fusion and thickening of podocyte pedicles but in some cases couldn,t maintain the 3 layer form of GBM. Octreotide had little effect on inhibition of fusion and thickening of podocyte pedicles and no effect in 3 layer form maintaining of GBM. Combined therapy inhibited fusion and thickening of podocyte pedicles and maintained 3 layer form of GBM but in some cases the lamina rara near endothelium was not seen. Octreotide have little effect on prevention of glomerular epithelium lesions. However Losartan could prevent glomerular epithelium lesions well, but combined drug therapy showed better results comparing Losartan.