The Effect of Co-administration of 4-Methylcatechol and Progesterone on Sciatic Nerve Function and Neurohistological Alterations in Streptozotocin-Induced Diabetic Neuropathy in Rats

Diabetic neuropathy is the most common complication of diabetes mellitus affecting the nervous system. In this study, we investigated the in vivo effects of combined administration of 4-methylcatechol (4-MC) and progesterone (P) as a potential therapeutic tool for sciatic nerve function improvement and its role in histomorphological alterations in diabetic neuropathy in rats. Male adult rats were divided into 3 groups: sham operated control (CO), untreated diabetic (DM) and diabetic treated with progesterone and 4-methylcatechol (DMP4MC) groups. Diabetes was induced by a single dose injection of 55 mg/kg streptozotocin (STZ). Four weeks after the STZ administration, the DMP4MC group was treated with P and 4-MC for 6 weeks. Then, following anesthesia, the animal's sciatic nerves were removed and processed for light and transmission electron microscopy (TEM) as well as histological evaluation. Diabetic rats showed a statistically significant reduction in motor nerve conduction velocity (MNCV), nerve blood flow (NBF), mean myelinated fiber (MF) diameters and myelin sheath thickness of the sciatic nerve after 10 weeks. In the sciatic nerve of the untreated diabetic group, endoneurial edema and increased number of myelinated fibers with myelin abnormalities such as infolding into the axoplasm, irregularity of fibers and alteration in myelin compaction were also observed. Treatment of diabetic rats with a combination of P and 4-MC significantly increased MNCV and NBF and prevented endoneurial edema and all myelin abnormalities. Our findings indicated that co-administration of P and 4-MC may prevent sciatic nerve dysfunction and histomorphological alterations in experimental diabetic neuropathy.