28-HOMOCASTASTERONE ATTENUATED DIABETIC KIDNEY DISEASE BY MODULATING LIVER X RECEPTOR AND TUMOR NECROSIS FACTOR-ALPHA PROTEIN EXPRESSION IN STZ-INDUCED DIABETIC RAT.

Athithan Velan and Srikumar Kotteazeth*

ABSTRACT

28-Homocastasterone (28-HC) exhibited antiglycemic and antilipidemic effects in diabetic rat. In the present study evaluated 28-HC effects on Liver x Receptor (LxR) mRNA expression, antioxidant status and histomorphological changes in diabetic rat kidney. Induction of diabetes was achieved by a single peritoneal injection of STZ (60 mg/kg. bwt) and 100 μg of 28-HC were administrated orally for 15 days. Followed by tissue malondialdehyde (MDA), superoxide dismutase (SOD), catalase, reduced glutathione (GSH), tumor necrosis factor-α (TNF-α), LxR-α, β mRNA and protein expression, tissue histomorphology were analysed along with 28-HC affinity towards inhibitor binding side of COX2 enzyme were evaluated using molecular simulation software. Increased SOD, catalase, reduced GSH, LxR-α and β mRNA levels were noted and reduced levels of MDA and TNF-α protein were registered in 28-HC treated diabetic rat. Kidney histology observed that glomerular damage reduced in 28-HC treated diabetic rat, In Silico analyses detected 28-HC have significant affinity towards inhibitor binding site of COX2 enzyme. 28-HC enhancing antioxidant enzymes catalytic activity thus attenuated lipid peroxidation and glomerular damage through transactivation of LxR and inhibition of COX2 enzyme catalytic activity. It is suggested that 28-HC supplemented diet prevent diabetic renal disease in man.

Keywords: 28-Homocastasterone, Diabetic, Kidney, LxR, COX2.