Neuroprotective effect of melatonin in a rat model of streptozotocin-induced diabetic neuropathy: Light and electron microscopic study

ABSTRACT

Diabetes mellitus [DM] is the most common cause of peripheral neuropathy in most countries. Oxidative stress appears to be the most important pathogenic factor in underlying diabetic complications, including neuropathy. The present study aimed to investigate the possible neuroprotective effects of melatonin [MLT] in a rat model of streptozotocin [STZ]-induced diabetic neuropathy. Thirty-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 by a single intraperitoneal injection of STZ at a dose of 60 mg/kg body weight and rats were sacrificed after 6 weeks. Rats in group III [n=15] were rendered diabetic by a single intraperitoneal injection of STZ, and immediately after confirmation of DM, that is, 48 h after STZ [random blood sugar > 200 mg/dl], rats received MLT at a dose of 10 mg/kg/day by intraperitoneal injection for 6 weeks. Body weight and random blood sugar were measured for all groups. Sciatic nerves of all the sacrificed animals were subjected to light microscopic, electron microscopic, and morphometric studies. In group II, DM induction was associated with the occurrence of neuropathy manifested by marked thickening of the epineurium and perineurium. Nerve fibers exhibited marked axonal atrophy, axonal shrinkage, axon-myelin separation, and in some sections total axonal destruction. Severe demyelination with evidence of myelin destruction was observed in the form of splitting and decompaction of myelin sheath lamellae, as well as vacuolization of the myelin sheath, forming fermentation chambers. In the MLT-treated group, vacuolization of the myelin sheath decreased remarkably and mild local axon separation from myelin sheaths was detected. Morphometric analysis revealed a significant increase in the number of total and apparently normal fibers and decrease in the number of apparently degenerated fibers in the nerve sections of MLT-treated rats, compared with nontreated diabetic rats. This study showed that MLT, in early stages of DM induction, decreased the destructive progress of DM and provided neuroprotection against damage resulting from STZ-induced hyperglycemia. Thus, it is recommended to start MLT therapy as soon as diagnosis of DM is established and even earlier in individuals at high risk for developing DM