title: Protective effect of L-glutamine against diabetes-induced nephropathy in experimental animal: Role of KIM-1, NGAL, TGF-β1, and collagen-1.
abstract: Diabetic nephropathy is a serious microvascular complication and one of the main causes of end-stage renal disease. L-Glutamine (LG) is naturally occurring amino acids with antidiabetic and antioxidant potential. The aim of present investigation was to evaluate the potential of LG against streptozotocin (STZ)-induced diabetic nephropathy (DN) in laboratory rats. DN was induced in male Wistar rats (200-220 g) by intraperitoneal administration of STZ (55 mg/kg). Animals were treated orally with either distilled water (10 mg/kg) or LG (250, 500, and 1000 mg/kg) or Sitagliptin (5 mg/kg). Various biochemical, molecular, and histological (hematoxylin-eosin and Masson's trichrome stain) parameters were assessed. Administration of LG (500 and 1000 mg/kg) significantly inhibited (p < .05) STZ-induced alterations in serum and urine biochemistry (urine creatinine, uric acid, albumin, and BUN). It also significantly increased creatinine clearance rate. STZ induced increase in renal oxidonitrosative stress was significantly decreased (p < .05) by LG (500 and 1000 mg/kg) treatment. Upregulated renal KIM-1, NGAL, TGF-β1, and collagen-1 mRNA expression after STZ administration was significantly inhibited (p < .05) by LG (500 and 1000 mg/kg) treatment. Correlation analysis also revealed that antidiabetic potential of LG attenuates STZ-induced elevated renal KIM-1, NGAL, TGF-β1, and collagen-1 mRNA expression. Histopathological alteration induced by STZ in renal tissue was ameliorated by LG treatment. In conclusion, results of present investigation suggest that treatment with LG ameliorated STZ-induced DN via the inhibition of oxidonitrosative stress as well as downregulation of KIM-1, NGAL, TGF-β1, and collagen-1 mRNA expressions.
authors.affiliation: a Padmashree Dr D. Y. Patil College of Pharmacy , Akurdi , Pune , Maharashtra , India.
authors.forename: Smeeta
authors.initials: S
authors.lastname: Sadar
authors.affiliation: b Cognizant Technology Solution , Hinjewadi, Pune , Maharashtra , India.
authors.forename: Dipti
authors.initials: D
authors.lastname: Kaspate
authors.affiliation: a Padmashree Dr D. Y. Patil College of Pharmacy , Akurdi , Pune , Maharashtra , India.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Vyawahare
mesh_terms: D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics*; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics*; D003921:Diabetes Mellitus, Experimental; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005973:Glutamine / Q000494:pharmacology*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D012313:RNA / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D015815:Cell Adhesion Molecules; D024042:Collagen Type I; D005973:Glutamine; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D012313:RNA; D053773:Transforming Growth Factor beta1; C110936:Havcr1 protein, rat; C097278:Lcn2 protein, rat
keywords: Diabetic nephropathy; KIM-1; L-glutamine; NGAL; TGF-β1; collagen-1; oxido-nitrosative stress