Gallotannin ameliorates the development of streptozotocin-induced diabetic nephropathy by preventing the activation of PARP.
Poly(ADP-ribose) polymerase (PARP) is known to be activated under conditions of oxidative stress and/or radiation exposure. The role of this enzyme has been well demonstrated in the streptozotocin (STZ) induced model of diabetes. Inhibition of PARP by specific inhibitors is known to prevent the development of STZ induced diabetic nephropathy by reduction in oxidative stress induced apoptosis. This study shows for the first time the role of poly(ADP-ribose) glycohydrolase (PARG) inhibitors as an alternative approach for inhibition of PARP. Gallotannin (20 mg/kg/day, i.p.) treatment for 4 weeks led to a significant reduction in the levels of plasma creatinine which is a well known marker for diabetic nephropathy. Treatment with gallotannin resulted in protection up to a certain level of glomerular damage, suggesting compensatory glomerular hypertrophy. As a PARG inhibitor gallotannin treatment also showed protection in PARP cleavage which is a hallmark for apoptotic cell death signifying the protective role of gallotannin in cell death signaling.
Chandak
Prakash Gopaldas
PG
Laboratory of Chromatin Biology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar (Mohali) - 160 062, Punjab, India.
Gaikwad
Anil Bhanudas
AB
Tikoo
Kulbhushan
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control*; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D007668:Kidney / Q000503:physiopathology; D008297:Male; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D047348:Hydrolyzable Tannins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D003404:Creatinine; D011065:Poly(ADP-ribose) Polymerases