Neuroprotective effect of melatonin in a rat model ofstreptozotocin-induced diabetic neuropathy: Light andelectron microscopic study

IntroductionDiabetes mellitus (DM) is the most common cause of peripheral neuropathy inmost countries. Oxidative stress appears to be the most important pathogenicfactor in underlying diabetic complications, including neuropathy.Aim of the workThe present study aimed to investigate the possible neuroprotective effectsof melatonin (MLT) in a rat model of streptozotocin (STZ)-induced diabeticneuropathy.Materials and methodsThirty-six (15 weeks old) adult male albino rats were divided into three groups.Group I (n=6) served as the control group. In group II (n=15), DM was induced bya single intraperitoneal injection of STZ at a dose of 60 mg/kg body weight and ratswere sacrificed after 6 weeks. Rats in group III (n=15) were rendered diabetic by asingle intraperitoneal injection of STZ, and immediately after confirmation of DM, thatis, 48 h after STZ (random blood sugar 200 mg/dl), rats received MLT at a doseof 10 mg/kg/day by intraperitoneal injection for 6 weeks. Body weight and randomblood sugar were measured for all groups. Sciatic nerves of all the sacrificed animalswere subjected to light microscopic, electron microscopic, and morphometric studies.ResultsIn group II, DM induction was associated with the occurrence of neuropathymanifested by marked thickening of the epineurium and perineurium. Nerve fibersexhibited marked axonal atrophy, axonal shrinkage, axon–myelin separation, andin some sections total axonal destruction. Severe demyelination with evidence ofmyelin destruction was observed in the form of splitting and decompaction of myelinsheath lamellae, as well as vacuolization of the myelin sheath, forming fermentationchambers. In the MLT-treated group, vacuolization of the myelin sheath decreasedremarkably and mild local axon separation from myelin sheaths was detected.Morphometric analysis revealed a significant increase in the number of total andapparently normal fibers and decrease in the number of apparently degeneratedfibers in the nerve sections of MLT-treated rats, compared with nontreated diabeticrats.ConclusionThis study showed that MLT, in early stages of DM induction, decreased thedestructive progress of DM and provided neuroprotection against damage resultingfrom STZ-induced hyperglycemia. Thus, it is recommended to start MLT therapy assoon as diagnosis of DM is established and even earlier in individuals at high risk fordeveloping DM.