Hypoglycemic action of vitamin K1 protects against early-onset diabetic nephropathy in streptozotocin-induced rats.
OBJECTIVE
Vitamin K is a potent regulator of vascular dynamics and prevents vascular calcification. Vitamin K is increasingly being recognized for its antioxidant and antiinflammatory properties. Recently we demonstrated that vitamin K1 (5 mg/kg) protects against streptozotocin-induced type 1 diabetes and diabetic cataract. The aim of this study was to determine whether the hypoglycemic action of vitamin K1 could inhibit early-onset diabetic nephropathy in a streptozotocin-induced rat kidney.


METHODS
Male Wistar rats were administered with 35 mg/kg STZ and after 3 days were treated with vitamin K1 (5 mg/kg, twice a week) for 3 months. Blood glucose was monitored once a month. At the end of the study, animals were sacrificed and kidney was dissected out and analysed for free radicals, antioxidants, aldose reductase, membrane ATPases, histopathology evaluation and expression of pro- and anti-inflammatory cytokines. Urea, uric acid, creatinine, albumin and insulin levels were also estimated.


RESULTS
Treatment of diabetic rats with vitamin K1 resulted in a decrease in blood glucose and prevented microalbuminuria. Vitamin K1 also reduced oxidative stress and protected renal physiology by modulating Ca(2+) and Na(+)/K(+)-ATPases. Vitamin K1 inhibited renal inflammation by reducing nuclear factor-κB and inducible nitric oxide synthase. Interleukin-10 levels were increased in renal tissues, suggesting the ability of vitamin K1 to trigger antiinflammatory state. The hypoglycemic action of vitamin K1 could have an indirect effect by inhibiting early-onset diabetic nephropathy triggered by high blood glucose.


CONCLUSIONS
Vitamin K1 could be an important nutrient based interventional strategy for early onset diabetic nephropathy.
Department of Bioengineering School of Chemical & Biotechnology, SASTRA University, Thanjavur, India.
M K N
MK
Sai Varsha
Department of Bioengineering School of Chemical & Biotechnology, SASTRA University, Thanjavur, India; Centre for Research on Infectious Diseases (CRID), School of Chemical & Biotechnology, SASTRA University, Thanjavur, India. Electronic address: raman@biotech.sastra.edu.
Thiagarajan
T
Raman
Department of Zoology, University of Madras, Guindy Campus, Chennai, India.
R
R
Manikandan
Department of Zoology, University of Madras, Guindy Campus, Chennai, India.
G
G
Dhanasekaran
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007668:Kidney / Q000276:immunology / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D010837:Vitamin K 1 / Q000494:pharmacology*; D014815:Vitamins / Q000494:pharmacology*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D016328:NF-kappa B; D014815:Vitamins; D010837:Vitamin K 1; D052247:Nitric Oxide Synthase Type II
Diabetes; Diabetic nephropathy; Inflammation; Kidney; Microalbuminuria; Vitamin K