TITLE:
Protective Effects of Combined Therapy of Rutin with Silymarin on Experimentally-Induced Diabetic Neuropathy in Rats
AUTHORS:
Maher M. Al-Enazi
KEYWORDS:
Rutin, Silymarin, Diabetic Neuropathy, Oxidative Stress, Inflammation
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.5 No.9,
August
19,
2014
ABSTRACT: The management of diabetic
neuropathy (DN) is still a challenge for physicians. Hyperglycemia induced
oxidative stress involves in the development of diabetic neuropathy, which
could be reversed by supplementation of antioxidants. In the present study, it
has targeted the oxidative stress mediated nerve damage in DN by using combined
therapy of rutin (RT) and silymarin (SM). Diabetes was induced by single
streptozotocin (STZ, 65 mg/kg i.p.) injection. The diabetic rats were treated
daily with RT (100 mg/kg), SM (60 mg/kg) and RT (50 mg/kg) + SM (30 mg/kg) for
6 consecutive weeks. Pain-related behavior tests were performed including tail
flick, paw-pressure analgesia and Rota-rod treadmill performance. Serum
glucose, insulin, tumor necrosis factor-α (TNF-α), interleukine-6 (IL-6) and
interleukine-1β (IL-β) levels were estimated. Thiobarbituric
acid reactive substances (TBARS), reduced glutathione (GSH) levels and
enzymatic activities of superoxide dismutase (SOD), catalase (CAT),
glutathione-S-transferase (GST), glutathione reductase (GR) and glutathione
peroxidase (GPx) were measured. Diabetic rats that developed neuropathy were
revealed by decreased tail-flick latency, paw-withdrawal latency and motor
coordination. RT (100 mg/kg/day) and SM (60 mg/kg/day) dosed to diabetic rats,
ameliorated hyperalgesia, analgesia and led to improved motor coordination.
However, the combined therapy of RT (50 mg/kg/day) with SM (30 mg/kg/day)
showed more significant effects in these parameters. STZ significantly
increased TBARS and decreased GSH levels in sciatic nerve whereas combined therapy
of RT and SM produced higher significant protection compared to individual.
Similarly, combined therapy showed more significant amelioration in decreased
levels of SOD, CAT, GST, GS and GPx activities in sciatic nerve of diabetic
rats. Present results concluded that the combined therapy of phenolic compounds
such as RT and SM had higher protective effects than their individual
supplementations against DM.