Restoration of ultrastructural and biochemical changes in alloxan-induced diabetic rat sciatic nerve on treatment with Na3VO4 and Trigonella--a promising antidiabetic agent.
Vanadium has been reported to have broad pharmacological activity both in vitro and in vivo. Vanadium compound, sodium orthovanadate, Na3VO4, is well known for its hypoglycaemic effects. However, Na3VO4 exerts these effects at relatively high doses (0.6 mg/ml) and exhibit several toxic effects. In the present study lower doses of Na3VO4 (0.2 mg/ml) are combined with Trigonella foenum graecum seed powder (TSP), another hypoglycaemic agent, to reduce its toxicity without compromising its antidiabetic potential. The efficacy of the lower doses of Na3VO4 has been investigated in restoring the altered glucose metabolism and histological structure in the sciatic nerves in 21 and 60 days alloxan diabetic rats. A portion of the glucose was found to be channelled from the normal glycolytic route to polyol pathway, evident by the reduced hexokinase activity and increased polyol pathway enzymes aldose reductase and sorbitol dehydrogenase activity causing accumulation of sorbitol and fructose in diabetic conditions. Ultrastructural observation of the sciatic nerve showed extensive demylination and axonal loss after eight weeks of diabetes induction. Blood glucose levels increased in diabetic rats were normalized with the lower dose of vanadium and Trigonella treatment. The treatment of the diabetic rats with vanadium and Trigonella prevented the activation of the polyol pathway and sugar accumulations. The sciatic nerves were also protected against the structural abnormalities found in diabetes with Trigonella foenum graecum as well as Na3VO4. Results suggest that lower doses of Na3VO4 may be used in combination with TSP as an efficient antidiabetic agent to effectively control the long-term complications of diabetes in tissues like peripheral nerve.
Preet
Anju
A
Hormone and Drug Research Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Gupta
Bihari L
BL
Siddiqui
Mohamed R
MR
Yadava
Pramod K
PK
Baquer
Nazma Zaheer
NZ
D000449:Aldehyde Reductase / Q000378:metabolism; D000496:Alloxan; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D005632:Fructose / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007064:L-Iditol 2-Dehydrogenase / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008517:Phytotherapy; D028321:Plant Preparations / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D013012:Sorbitol / Q000378:metabolism; D029910:Trigonella / Q000737:chemistry*; D014638:Vanadates / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D028321:Plant Preparations; D005632:Fructose; D014638:Vanadates; D013012:Sorbitol; D000496:Alloxan; D007064:L-Iditol 2-Dehydrogenase; D000449:Aldehyde Reductase; D005954:Glucosephosphate Dehydrogenase; D006593:Hexokinase; D005978:Glutathione