Tocotrienol ameliorates behavioral and biochemical alterations in the rat model of alcoholic neuropathy.
Chronic alcohol consumption produces a painful peripheral neuropathy for which there is no reliable successful therapy, which is mainly due to lack of understanding of its pathobiology. Alcoholic neuropathy is characterized by spontaneous burning pain, hyperalgesia (an exaggerated pain in response to painful stimuli) and allodynia (a pain evoked by normally innocuous stimuli). Chronic alcohol intake is known to decrease the nociceptive threshold with increased oxidative-nitrosative stress and release of proinflammatory cytokines coupled with activation of protein kinase C. The aim of the present study is to investigate the effect of both isoforms of vitamin E, alpha-tocopherol (100mg/kg; oral gavage) and tocotrienol (50, 100 and 200mg/kg; oral gavage) against alcohol-induced neuropathic pain in rats. Male Wistar rats, were administered 35% v/v ethanol (10 g/kg; oral gavage) for 10 weeks, and were treated with alpha-tocopherol and tocotrienol for the same duration. Ethanol-treated animals showed a significant decrease in nociceptive threshold as evident from decreased tail flick latency (thermal hyperalgesia) and decreased paw-withdrawal threshold in Randall-Sellito test (mechanical hyperalgesia) and von-Frey hair test (mechanical allodynia) along with the reduction in nerve glutathione and superoxide dismutase levels. TNF-alpha and IL-1beta levels were also significantly increased in both serum and sciatic nerve of ethanol-treated rats. Treatment with alpha-tocopherol and tocotrienol for 10 weeks significantly improved all the above-stated functional and biochemical deficits in a dose-dependent manner with more potent effects observed with tocotrienol. The study demonstrates the effectiveness of tocotrienol in attenuation of alcoholic neuropathy.
Tiwari
Vinod
V
Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Center of Advanced Study, Panjab University, Chandigarh-160 014, India.
Kuhad
Anurag
A
Chopra
Kanwaljit
K
D020269:Alcoholic Neuropathy / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D053583:Interleukin-1beta / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D024508:Tocotrienols / Q000494:pharmacology* / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000975:Antioxidants; D053583:Interleukin-1beta; D024508:Tocotrienols; D014409:Tumor Necrosis Factor-alpha