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.
Abdelkader, N. F., A. M. abd El-latif, and M. M. Khattab, "Telmisartan/17β-estradiol mitigated cognitive deficit in an ovariectomized rat model of Alzheimer's disease: Modulation of ACE1/ACE2 and AT1/AT2 ratio.", Life sciences , vol. 245, pp. 117388, 2020.
Shahin, N. N., N. F. Abdelkader, and M. M. Safar, "A novel role of irbesartan in gastroprotection against indomethacin-induced gastric injury in rats: Targeting DDAH/ ADMA and EGFR/ERK Signaling", Scientific Reports, vol. 8, pp. 4280, 2018.
Kamel, A. S., N. F. Abdelkader, S. A. S. El-Rahman, M. Emara, H. F. Zaki, and M. M. Khattab, "Stimulation of ACE2/ANG(1-7)/Mas Axis by Diminazene Ameliorates Alzheimer's Disease in the D-Galactose-Ovariectomized Rat Model: Role of PI3K/Akt Pathway.", Molecular Neurobiology, vol. 55, pp. 8188-8202, 2018.
Leitch, A. C., T. M. Abdelghany, P. M. Probert, M. P. Dunn, S. K. Meyer, J. M. Palmer, M. P. Cooke, L. I. Blake, K. Morse, A. K. Rosenmai, et al., "The toxicity of the methylimidazolium ionic liquids, with a focus on M8OI and hepatic effects.", Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, vol. 136, pp. 111069, 2020. Abstract

Ionic liquids are a diverse range of charged chemicals with low volatility and often liquids at ambient temperatures. This characteristic has in part lead to them being considered environmentally-friendly replacements for existing volatile solvents. However, methylimidazolium ionic liquids are slow to break down in the environment and a recent study at Newcastle detected 1 octyl 3 methylimidazolium (M8OI) - an 8 carbon variant methylimidazolium ionic liquid - in soils in close proximity to a landfill site. The current M8OI toxicity database in cultured mammalian cells, in experimental animal studies and in model indicators of environmental impact are reviewed. Selected analytical data from the Newcastle study suggest the soils in close proximity to the landfill site, an urban soil lacking overt contamination, had variable levels of M8OI. The potential for M8OI - or a structurally related ionic liquid - to trigger primary biliary cholangitis (PBC), an autoimmune liver disease thought to be triggered by an unknown agent(s) in the environment, is reviewed.

Ibrahim, W. W., N. F. Abdelkader, H. M. Ismail, and M. M. Khattab, "Escitalopram Ameliorates Cognitive Impairment in D-Galactose-Injected Ovariectomized Rats: Modulation of JNK, GSK-3β, and ERK Signalling Pathways.", Scientific reports, vol. 9, issue 1, pp. 10056, 2019. Abstract

Though selective serotonin reuptake inhibitors (SSRIs) have been found to increase cognitive performance in some studies on patients and animal models of Alzheimer's disease (AD), other studies have reported contradictory results, and the mechanism of action has not been fully described. This study aimed to examine the effect of escitalopram, an SSRI, in an experimental model of AD and to determine the involved intracellular signalling pathways. Ovariectomized rats were administered D-galactose (150 mg/kg/day, i.p) over ten weeks to induce AD. Treatment with escitalopram (10 mg/kg/day, p.o) for four weeks, starting from the 7 week of D-galactose injection, enhanced memory performance and attenuated associated histopathological changes. Escitalopram reduced hippocampal amyloid β 42, β-secretase, and p-tau, while increasing α-secretase levels. Furthermore, it decreased tumor necrosis factor-α, nuclear factor-kappa B p65, and NADPH oxidase, while enhancing brain-derived neurotrophic factor, phospho-cAMP response element binding protein, and synaptophysin levels. Moreover, escitalopram diminished the protein expression of the phosphorylated forms of c-Jun N-terminal kinase (JNK)/c-Jun, while increasing those of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase-3β (GSK-3β), extracellular signal-regulated kinase (ERK) and its upstream kinases MEK and Raf-1. In conclusion, escitalopram ameliorated D-galactose/ovariectomy-induced AD-like features through modulation of PI3K/Akt/GSK-3β, Raf-1/MEK/ERK, and JNK/c-Jun pathways.

Eitah, H. E., Y. A. Maklad, N. F. Abdelkader, A. A. Gamal El Din, M. A. Badawi, and S. A. Kenawy, "Modulating impacts of quercetin/sitagliptin combination on streptozotocin-induced diabetes mellitus in rats.", Toxicology and applied pharmacology, vol. 365, pp. 30-40, 2019. Abstract

BACKGROUND: Since many diabetic patients require combination therapy, the use of herbal remedies with anti-diabetic activity represents a vital option in diabetes mellitus (DM) management. It has been reported that quercetin has hypoglycemic alongside anti-inflammatory and antioxidant activities.

AIM: The present study aimed to investigate the effectiveness of combining quercetin with sitagliptin; a selective dipeptidyl peptidase-IV (DPP-IV) inhibitor, in the management of streptozotocin (STZ)-induced diabetic rats.

METHODS: DM was induced by a single injection of STZ (45 mg/kg, i.p.) in male adult albino Wistar rats. Diabetic rats were orally treated with sitagliptin (70 mg/kg), quercetin (50 mg/kg) or their combination daily for three consecutive weeks. Serum levels of glucose, C-peptide, total cholesterol, triglycerides, malondialdehyde (MDA), superoxide dismutase, (SOD), reduced glutathione (GSH), tumor necrosis factor alpha, (TNF-α), nuclear factor kappa-B, (NF-κB) and adiponectin were estimated. In addition, histopathological, morphometrical and immunohistochemical examinations of pancreatic tissues were conducted.

RESULTS: The combined administration of quercetin and sitagliptin normalized serum C-peptide, MDA, and significantly increased SOD, GSH and decreased NF-κB more than sitagliptin alone. Moreover, this combination normalized Islet number, β-cells' number, area and perimeter alongside restoring the immunostaining intensity of β-cells.

CONCLUSION: Our results suggest the use of quercetin/sitagliptin combination for treating DM based on the observed improvements in glycemic control, metabolic profile, oxidative and inflammatory status, islet structure as well as β-cells function compared with either treatment alone.

Moustafa, P. E., N. F. Abdelkader, S. A. El Awdan, O. A. El-Shabrawy, and H. F. Zaki, "Extracellular Matrix Remodeling and Modulation of Inflammation and Oxidative Stress by Sulforaphane in Experimental Diabetic Peripheral Neuropathy.", Inflammation, vol. 41, issue 4, pp. 1460-1476, 2018 Aug. Abstract

The peripheral nervous system is one of many organ systems that can be profoundly impacted in diabetes mellitus. Diabetic peripheral neuropathy has a significant negative effect on patients' quality of life as it begins with loss of limbs' sensation and may result in lower limb amputation. This investigation aimed at exploring the effect of sulforaphane on peripheral neuropathy in diabetic rats. Experimental diabetes was induced through single intraperitoneal injections of nicotinamide (50 mg/kg) and streptozotocin (52.5 mg/kg). Rats were divided into five groups. Two groups were treated with saline or sulforaphane (1 mg/kg, p.o.). Three diabetic groups were either untreated or given sulforaphane (1 mg/kg, p.o.) or pregabalin (10 mg/kg, i.p.). Two weeks after drugs' administration, biochemical, behavioral, histopathological, and immunohistochemical investigations were carried out. Treatment with sulforaphane restored animals' body weight, reduced blood glucose, glycated hemoglobin, and increased insulin levels. In parallel, it normalized motor coordination and the latency withdrawal time of tail flick test, increased the latency withdrawal time of cold allodynia test, and ameliorated histopathological changes. Treatment of sulforaphane, likewise, decreased sciatic nerve malondialdehyde, nitric oxide, interleukin-6, and matrix metalloproteinase-2 and -9 contents. Similarly, it reduced sciatic nerve DNA fragmentation and expression of cyclooxygenase-2 and nuclear factor kappa-B p65. Meanwhile, it increased sciatic nerve superoxide dismutase and interleukin-10 contents. These results reveal the neuroprotective effect of sulforaphane against peripheral neuropathy in diabetic rats possibly through modulating oxidative stress, inflammation, and extracellular matrix remodeling. Graphical Abstract Diagram that illustrates the effects of sulforaphane in treating experimental diabetic peripheral neuropathy. In NA-STZ model of diabetes mellitus, sulforaphane, restored animals' body weight, reduced blood glucose, glycated hemoglobin and increased insulin levels. In parallel, it normalized motor coordination and the latency withdrawal time of tail flick test, increased the latency withdrawal time of cold allodynia test and ameliorated histopathological changes. Treatment of sulforaphane, likewise, decreased sciatic nerve malondialdehyde, nitric oxide, interleukin-6, matrix metalloproteinase-2 and -9 contents. Similarly, it reduced sciatic nerve DNA fragmentation and expression of cyclooxygenase-2 and nuclear factor kappa-B p65. Meanwhile, it increased sciatic nerve superoxide dismutase and interleukin-10 contents.

Moustafa, P. E., N. F. Abdelkader, S. A. El Awdan, O. A. El-Shabrawy, and H. F. Zaki, "Liraglutide ameliorated peripheral neuropathy in diabetic rats: Involvement of oxidative stress, inflammation and extracellular matrix remodeling.", Journal of neurochemistry, vol. 146, issue 2, pp. 173-185, 2018 Jul. Abstract

Diabetic peripheral neuropathy is one of the most common microvascular complications that occurs with both type 1 and type 2 diabetes mellitus. It has a significant negative impact on patients' quality of life; as it starts with loss of limbs' sensation and may lead to lower limb amputation. This study aimed at investigating the effect of liraglutide on peripheral neuropathy in diabetic rats. Experimental diabetes was induced by single intraperitoneal injections of nicotinamide (50 mg/kg) and streptozotocin (52.5 mg/kg). Rats were allocated into five groups. Two groups were given saline or liraglutide (0.8 mg/kg, s.c.). Three diabetic groups were either untreated or treated with liraglutide (0.8 mg/kg, s.c.) or pregabalin (10 mg/kg, i.p.). After 2 weeks of treatment, behavioral, biochemical, histopathological, and immunohistochemical investigations were performed. Treatment with liraglutide-restored animals' body weight, normalized blood glucose, decreased glycated hemoglobin, and increased insulin levels. In parallel, it normalized motor coordination and the latency withdrawal time of both tail flick and hind paw cold allodynia tests and reversed histopathological alterations. Treatment with liraglutide also normalized malondialdehyde, matrix metalloproteinase-2 and -9 contents in sciatic nerve. Likewise, it decreased sciatic nerve nitric oxide and interleukin-6 contents, DNA fragmentation and expression of cyclooxygenase-2. Meanwhile, it increased superoxide dismutase and interleukin-10 contents in sciatic nerve. These findings indicate the neuroprotective effect of liraglutide against diabetic peripheral neuropathy probably via modulating oxidative stress, inflammation, and extracellular matrix remodeling.

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