Neuroprotective effect of mexiletine in the central nervous system of diabetic rats.
Both experimental and clinical studies suggests that oxidative stress plays an important role in the pathogenesis of diabetes mellitus type 1 and type 2. Hyperglycaemia leads to free radical generation and causes neural degeneration. In the present study we investigated the possible neuroprotective effect of mexiletine against streptozotocin-induced hyperglycaemia in the rat brain and spinal cord. 30 adult male Wistar rats were divided into three groups: control, diabetic, and diabetic-mexiletine treated group. Diabetes mellitus was induced by a single injection of streptozotocin (60 mg/kg body weight). Mexiletine (50 mg/kg) was injected intraperitoneally every day for six weeks. After 6 weeks the brain, brain stem and cervical spinal cord of the rats were removed and the hippocampus, cortex, cerebellum, brain stem and spinal cord were dissected for biochemical analysis (the level of Malondialdehide [MDA], Nitric Oxide [NO], Reduced Glutathione [GSH], and Xanthine Oxidase [XO] activity). MDA, XO and NO levels in the hippocampus, cortex, cerebellum, brain stem and spinal cord of the diabetic group increased significantly, when compared with control and mexiletine groups (P < 0.05). GSH levels in the hippocampus, cortex, cerebellum, brain stem and spinal cord of the diabetic group decreased significantly when compared with control and mexiletine groups (P < 0.05). This study demonstrates that mexiletine protects the neuronal tissue against the diabetic oxidative damage.
Inonu University, School of Medicine, Department of Neurosurgery, Malatya, Turkey. atesozkan@hotmail.com
Ozkan
O
Ates
Suleyman R
SR
Cayli
Eyup
E
Altinoz
Neslihan
N
Yucel
Ayhan
A
Kocak
Ozcan
O
Tarim
Akif
A
Durak
Yusuf
Y
Turkoz
Saim
S
Yologlu
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism* / Q000517:prevention & control; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008801:Mexiletine / Q000008:administration & dosage / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014969:Xanthine Oxidase / Q000378:metabolism
D001786:Blood Glucose; D018696:Neuroprotective Agents; D008801:Mexiletine; D009569:Nitric Oxide; D008315:Malondialdehyde; D014969:Xanthine Oxidase