Objectives: The current study examined the effects of new antihyperglycemic drugs (GLP1 analogue, semaglutide) and SGLT2 inhibitor; dapagliflozin) on nerve functions and morphology in obese rats as well as their underlying mechanisms.
Methods: 40 male Sprague Dawley rats, aged 6-8 weeks and classified into 5 groups; normal group, high-fat diet (HFD): HFD for 12 weeks, Metformin group: HFD for 12 weeks + metformin in last 4 weeks, DAPA group: HFD for 12 weeks +dapagliflozin in last 4 weeks, semaglutide group: HFD for 12 weeks + semaglutide in last 4 weeks. At the end of the experiment, sciatic nerve was collected for nerve conduction study, oxidative stress marker (MDA), real time PCR study (for HO-1 and Nrf2), red o oil staining, electron microscopic examination and immunohistochemistry for NGF and synaptophysin.
Results: HFD group showed significant rise in blood glucose, serum lipids, HOMA index, lipid deposition in nerve tissues and lipid peroxidation (MDA) in nerve tissues with significant attenuation in NCV, the expression of Nrf2 and HO-1 genes and significant attenuation in area stained with NGF and synaptophysin. On the other hand, pretreatment with either DAPA or semaglutide led to considerable enhancement in the deteriorated serum and nerve tissue parameters and reverse the pathological changes.
Conclusion: New antidiabetic drugs like SGLT2 inhibitors (more powerful) and GLP1 analogue might have neuroprotective beneficial effects beside controlling the glycemic state in obese rats. This effect may result from reduced oxidative stress and increased Nrf2 levels., HO-1, synaptophysin and NGF in nerve tissues of obese rats.
Keywords: nerve conduction velocity, obese, Nrf2, HO-1, NGF, synaptophysin, DAPA, semaglutide.
A. Hussein: None. E.M. Eid: None. Y.M. Yehya: None. M. Taha: None. A.A.H. Mosa: None. O.A. Ammar: None. N.H. Abdel-Halim: None.
