Abdelkader, N. F., S. M. Ibrahim, P. E. Moustafa, and M. A. Elbaset, "Inosine mitigated diabetic peripheral neuropathy via modulating GLO1/AGEs/RAGE/NF-κB/Nrf2 and TGF-β/PKC/TRPV1 signaling pathways.", Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, vol. 145, pp. 112395, 2022. Abstract

Inosine is a dietary supplement that is widely used for managing numerous central neurological disorders. Interestingly, recent experimental investigation of inosine revealed its potential to promote peripheral neuroprotection after sciatic nerve injury. Such investigation has guided the focus of the current study to expose the potential of inosine in mitigating diabetic peripheral neuropathy (DPN) in rats and to study the possible underlying signaling pathways. Adult male Wistar rats were arbitrarily distributed into four groups. In the first group, animals received saline daily for 15 days whereas rats of the remaining groups received a single injection of both nicotinamide (50 mg/Kg/i.p.) and streptozotocin (52.5 mg/Kg/i.p.) for DPN induction. Afterward, inosine (10 mg/Kg/p.o.) was administered to two groups, either alone or in combination with caffeine (3.75 mg/Kg/p.o.), an adenosine receptor antagonist. As a result, inosine showed a hypoglycemic effect, restored the sciatic nerve histological structure, enhanced myelination, modulated conduction velocities and maintained behavioral responses. Furthermore, inosine increased GLO1, reduced AGE/RAGE axis and oxidative stress which in turn, downregulated NF-κB p65 and its phosphorylated form in the sciatic nerves. Inosine enhanced Nrf2 expression and its downstream molecule HO-1, resulting in increased CAT and SOD along with lowered MDA. Moreover, pain was relieved due to suppression of PKC and TRPV1 expression, which ultimately lead to reduced SP and TGF-β. The potential effects of inosine were nearly blocked by caffeine administration; this emphasizes the role of adenosine receptors in inosine-mediated neuroprotective effects. In conclusion, inosine alleviated hyperglycemia-induced DPN via modulating GLO1/AGE/RAGE/NF-κB p65/Nrf2 and TGF-β/PKC/TRPV1/SP pathways.

Saad, M. A., M. A. E. Ahmed, N. N. Elbadawy, and N. F. Abdelkader, "Nano-ivabradine averts behavioral anomalies in Huntington's disease rat model via modulating Rhes/m-tor pathway.", Progress in neuro-psychopharmacology & biological psychiatry, vol. 111, pp. 110368, 2021. Abstract

Huntington's disease (HD) is characterized by abnormal involuntary movements together with cognitive impairment and disrupted mood changes. 3-nitropropionic acid (3-NP) is one of the chemo-toxic models used to address the striatal neurotoxicity pattern encountered in HD. This study aims to explain the neuroprotective effect of nano-formulated ivabradine (nano IVA) in enhancing behavioral changes related to 3-NP model and to identify the involvement of ras homolog enriched striatum (Rhes)/mammalian target of rapamycin (m-Tor) mediated autophagy pathway. Rats were divided into 6 groups, the first 3 groups received saline (control), ivabradine (IVA), nano IVA respectively, the fourth received a daily dose of 3-NP (20 mg/kg, s.c) for 2 weeks, the fifth received 3-NP + IVA (1 mg/kg, into the tail vein, every other day for 1 week) and the last group received 3-NP + nano IVA (1 mg/kg, i.v, every other day for 1 week). Interestingly, nano IVA reversed motor disabilities, improved memory function and overcame the psychiatric changes. It boosted expression of autophagy markers combined with down regulation of Rhes, m-Tor and b-cell lymphoma 2 protein levels. Also, it restored the normal level of neurotransmitters and myocardial function related-proteins. Histopathological examination revealed a preserved striatal structure with decreased number of darkly-degenerated neurons. In conclusion, the outcomes of this study provide a well-recognized clue for the promising neuroprotective effect of IVA and the implication of autophagy and Rhes/m-Tor pathways in the 3-NP induced HD and highlight the fact that nano formulations of IVA would be an auspicious approach in HD therapy.

Safar, M. M., N. F. Abdelkader, E. Ramadan, M. A. Kortam, and A. F. Mohamed, "Novel mechanistic insights towards the repositioning of alogliptin in Parkinson's disease.", Life sciences, vol. 287, pp. 120132, 2021. Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disease that impairs people's lives tremendously. The development of innovative treatment modalities for PD is a significant unmet medical need. The critical function of glucagon-like peptide-1 (GLP-1) in neurodegenerative diseases has raised impetus in investigating the repositioning of a dipeptidyl peptidase IV inhibitor, alogliptin (ALO), as an effective treatment for PD. As a result, the focus of this research was to assess the effect of ALO in a rat rotenone (ROT) model of PD. For 21 days, ROT (1.5 mg/kg) was delivered subcutaneously every other day. ALO (30 mg/kg/day), delivered by gavage for 21 days, recovered motor performance and improved motor coordination in the open-field and rotarod testing. These impacts were highlighted by restoring striatal dopamine content and correcting histological changes that occurred concurrently. The ALO molecular signaling was determined by increasing the quantity of GLP-1 and the protein expression of its downstream signaling pathway, pT172-AMPK/SIRT1/PGC-1α. Furthermore, it curbed neuroinflammation via hampering HMGB1/TLR4/NLRP3 inflammasome activation and conquered striatal microglia activation. Pre-administration of dorsomorphin reversed the neuroprotective effects. In conclusion, the promising neuroprotective effect of ALO highlights the repositioning of ALO as a prospective revolutionary candidate for combating PD.

Abdulwahab, D. K., W. W. Ibrahim, R. A. A. El-Aal, H. A. Abdel-Latif, and N. F. Abdelkader, "Grape Seed Extract Improved the Fertility-Enhancing Effect of Atorvastatin in High Fat Diet-Induced Testicular Injury in Rats: Involvement of Anti-oxidant and Anti-Apoptotic Effects", Journal of Pharmacy and Pharmacology, vol. 73, pp. 366-376, 2021.
Abdelkader, N., "Urso- and tauroursodeoxycholic acids as anti-apoptotic agents: Modulation of Parkinson's disease.", The Neuroscience of Parkinson's Disease: Diagnosis and Management in Parkinson's Disease : Academic Press, 2020.
Abdelkader, N. F., H. A. Farid, E. R. Youness, O. M. E. Abdel-Salam, and H. F. Zaki, "The role of KATP channel blockade and activation in the protection against neurodegeneration in the rotenone model of Parkinson’s disease", Life Sciences , vol. 257, pp. 118070, 2020.
Safar, M. M., N. N. Shahin, A. F. Mohamed, and N. F. Abdelkader, "Suppression of BACE1 and amyloidogenic/RAGE axis by sitagliptin ameliorates PTZ kindling-induced cognitive deficits in rats", Chemico-Biological Interactions, vol. 328, pp. 109144, 2020. Abstract

A double-blind study with intra-individual comparisons was carried out to investigate the effects of 15 mg of (8r)-3alpha-hydroxy-8-isopropyl-1alphaH-tropanium bromide(+/-)-tropate (Sch 1000), 15 mg Sch 1000 + 10 mg oxazepam, 10 mg oxazepam and placebo with oral administration in randomized sequence on gastric juice volume, amount of acid, concentration and pH values in 12 healthy volunteers. The secretion parameters were measured during a 1-h basal period and a 2-h stimulation period. The gastric juice was obtained in 15 min portions via stomach tube. Stimulation was effected by 1 mug/kg/h pentagastrin via drip infusion. The Friedman test was used for the comparative statistical evaluation, and individual comparisons were carried out by means of the Wilcoxon test (pair-differences rank). The results show that Sch 1000 and Sch 1000 + oxazepam were equal in effect on basal and stimulated secretion volume. As compared with placebo, it was not possible to establish an effect on secretion volume for oxazepam alone. Sch 1000 and Sch 1000 + oxazepam were found to be equipotent in reducing the amount of basal acid, while oxazepam reduced this quantity only during the first 30 min of basal secretion. None of the three active preparations was capable of inhibiting the stimulated acid, although both Sch 1000 preparations produced a clear trend towards lowered mean values. During the basal secretion period, all three test preparations had an inhibiting action on acid concentration, but none of them had a significant effect during the stimulation period. The pH value was savely increased only by Sch 1000 and Sch 1000 + oxazepam, and this even only during the basal period. The results are discussed.

Ibrahim, W. W., H. M. Ismail, M. M. Khattab, and N. F. Abdelkader, "Cognitive enhancing effect of diapocynin in D-galactose-ovariectomy-induced Alzheimer's-like disease in rats: Role of ERK, GSK-3β, and JNK signaling", Toxicology and Applied Pharmacology, vol. 398, pp. 115028, 2020.
Abdelkader, N. F., H. E. Eitah, Y. A. Maklad, A. A. Gamaleldin, M. A. Badawi, and S. A. Kenawy, "New combination therapy of gliclazide and quercetin for protection against STZ-induced diabetic rats.", Life sciences , vol. 247, pp. 117458, 2020.
Abdelkader, N. F., M. Elyamany, A. M. Gad, N. A. G. L. A. A. ASSAF, H. M. Fawzy, and W. H. Elesawy, "Ellagic acid attenuates liver toxicity induced by valproic acid in rats", Journal of Pharmacological Sciences, 2020.