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Fouad Shalaby, M., H. A. A. Latif, M. El Yamani, M. A. Galal, S. Kamal, and I. Sindi, "Protective Role of Sarpogrelate in Combination with Bromocriptine and Cabergoline for Treatment of Diabetes in Alloxan-induced Diabetic Rats.", Current therapeutic research, clinical and experimental, vol. 95, pp. 100647, 2021. Abstract

BACKGROUND: Although dopamine D receptor agonists, bromocriptine and cabergoline, are notable medications in the treatment of Parkinsonism, hyperprolactinemia, and hyperglycemia, there is an identified relationship between the utilization of D-like R agonists and the progress of myocardial injury, especially in the early phase of therapy.

OBJECTIVE: This investigation aimed to examine the potential activity of sarpogrelate (a 5-hydroxytryptamine 2A [5-HT2A] receptor blocker) in reducing myocardial injury prompted by extended haul utilization of D receptor agonists in a model of diabetic rats.

METHODS: In the in vivo studies, both bromocriptine and cabergoline were managed independently and combined with sarpogrelate for about a month in diabetic nephropathy rats. Blood glucose level and other myocardial biochemical parameters were estimated. The probable mechanism for insulin secretagogue action was evaluated through in vitro isolated islets study. Sodium/potassium-adenosine triphosphatase activity was assayed in an isolated microsomal fraction of the renal cortex. Isolated perfused rat hearts were treated with different doses of dopamine before and after being subjected to the tested drugs, dose response of heart rate, and heart contractility were recorded.

RESULTS: Bromocriptine and cabergoline created a significant reduction in blood glucose level without any action on insulin secretagogues. Bromocriptine prevented the loss of sodium/potassium-adenosine triphosphatase activity in the cortex of an ischemic kidney. Treatment of bromocriptine or cabergoline with sarpogrelate altogether decreased the levels of the elevated myocardial biomarkers in serum. Administration of different doses of dopamine in presence of bromocriptine or capergoline resulted in significantly rising in the heart rate percentage comparing to dopamine alone. A mix of bromocriptine or cabergoline with sarpogrelate diminished both heart rate and contractility, respectively.

CONCLUSIONS: The examination demonstrated that the combined use of sarpogrelate with bromocriptine or cabergoline decreased the potential adverse effects of these 2 drugs on myocardial tissues.

Abd El Fattah, M. A., Y. A. Abdelhamid, M. F. Elyamany, O. A. Badary, and O. A. Heikal, "Rice Bran Extract Protected against LPS-Induced Neuroinflammation in Mice through Targeting PPAR-γ Nuclear Receptor.", Molecular neurobiology, vol. 58, issue 4, pp. 1504-1516, 2021. Abstract

PPAR-γ anti-inflammatory functions have received significant attention since its agonists have been shown to exert a wide range of protective effects in many experimental models of neurologic diseases. Rice bran is very rich in polyunsaturated fatty acids, which are reported to act as PPAR-γ partial agonists. Herein, the anti-inflammatory effect of rice bran extract (RBE) through PPAR-γ activation was evaluated in LPS-induced neuroinflammatory mouse model in comparison to pioglitazone (PG) using 80 Swiss albino mice. RBE (100 mg/kg) and PG (30 mg/kg) were given orally for 21 days and LPS (0.25 mg/kg) was injected intraperitoneally for the last 7 days. TNF-α and COX-2 brain contents were evaluated by real-time PCR and immunohistochemical analysis. In addition, NFκB binding to its response element was evaluated alongside with the effect of treatments on IκB gene expression. Furthermore, PPAR-γ sumoylation was also studied. Finally, histopathological examination was performed for different brain areas. RBE administration was found to protect against the LPS-induced inflammatory effects by decreasing the inflammatory mediator expression in mice brains. It also decreased PPAR-γ sumoylation without significant effect on IκB expression or NFκB binding to its response element. The majority of the effects were attenuated in presence of PPAR-γ antagonist (GW9662). Level of significance was set to P < 0.05. Such findings highlight the agonistic effect of RBE component(s) on PPAR-γ and support the hypothesis of involvement of PPAR-γ activation in its neuroprotective effect.

Fouad Shalaby, M. A., H. A. Abdellatif, M. El Yamani, M. A. Galal, S. Kamal, I. Sindi, and R. Masaood, "Therapeutic activity of sarpogrelate and dopamine D receptor agonists on cardiovascular and renal systems in rats with alloxan-induced diabetes.", BMC pharmacology & toxicology, vol. 22, issue 1, pp. 64, 2021. Abstract

BACKGROUND: Dopamine D receptor agonists, bromocriptine and cabergoline, are notable medications in the treatment of Parkinsonism, hyperprolactinemia, and hyperglycemia. An affiliation was found between the initiation of myocardial injury ailment and long term treatment with dopamine D agonist drugs identified with the partial activation of 5-hydroxytryptamine receptor 2 A (5-HT2A). The investigation aimed to examine the activity of sarpogrelate (a 5-HT2A receptor blocker) in reducing myocardial injury prompted by extended haul utilisation of D receptor agonists in rats with alloxan-induced diabetes.

METHODS: Both bromocriptine and cabergoline were managed independently and combined with sarpogrelate for about a month in diabetic nephropathy rats. Both tail-cuff blood pressure and the BGL were recorded weekly. For all animals, the kidney hypertrophy index, serum creatinine, blood urea nitrogen, alanine transaminase, and aspartate transaminase levels were measured after one month of treatment. The severity of the cardiac injury was assessed by the estimation of lactate dehydrogenase-1 (LDH-1), cardiac troponin I, and tumor necrosis factor alpha 1 (TNF1). The triphenyltetrazolium chloride (TTC) staining method was used to determine the experimental myocardial infarction (MI) size.

RESULTS: Bromocriptine and cabergoline created a significant reduction in BGL, BP, and kidney hypertrophy index in diabetic nephropathy rats. Administration of bromocriptine and cabergoline, alone, or in combination with sarpogrelate fundamentally diminished the blood concentrations of alkaline phosphatase (ALP), Aspartate aminotransferase (AST), urea, and creatinine. Bromocriptine and cabergoline alone showed a noteworthy increase in the LDH-1, Troponin I, and TNF1 levels in the serum (p < 0.05). Paradoxically, utilising bromocriptine or cabergoline with sarpogrelate treatment altogether decreased the levels of the myocardial biomarkers in the serum. A mix of bromocriptine or cabergoline with sarpogrelate diminished the level of the myocardial infarct size in the heart assessed through the TTC staining method.

CONCLUSIONS: The examination demonstrated that the combined use of sarpogrelate with bromocriptine or cabergoline decreased the potential adverse effects of these two drugs on the myocardial tissues.

Gamil, N. M., M. A. Abd El Fattah, M. A. E. Ahmed, Y. A. Maklad, A. A. Gamal El Din, and N. I. Eid, "Lansoprazole enhances the antidiabetic effect of dapagliflozin in fortified diet-fed streptozotocin-treated diabetic rats.", Journal of biochemical and molecular toxicology, vol. 34, issue 4, pp. e22451, 2020. Abstract

Dapagliflozin (DAPA) is used for treating type 2 diabetes, whereas lansoprazole (LPZ) is used as a traditional antiulcer drug. The present study investigated the possible antidiabetic effects of LPZ on fortified diet-fed streptozotocin (FDF/STZ)-induced insulin-resistant diabetic rats. On the basis of the current results, it can be concluded that LPZ could be used as an add-on drug along with the conventional treatment for T2D as it showed beneficial effects in the current experimental model of insulin resistance.

Aziz, M. M., M. A. Abd El Fattah, K. A. Ahmed, and H. M. Sayed, "Protective effects of olmesartan and l-carnitine on doxorubicin-induced cardiotoxicity in rats.", Canadian journal of physiology and pharmacology, vol. 98, issue 4, pp. 183-193, 2020. Abstract

Doxorubicin (DOX), an anthracycline antibiotic, is an important antineoplastic agent due to its high antitumor efficacy in hematological as well as in solid malignancies. The clinical use of DOX is limited due to its cardiotoxic effects. The present study aimed to investigate the possible protective effect of olmesartan (Olm), l-carnitine (L-CA), and their combination in cardiotoxicity induced by DOX in rats. Male albino rats were randomly divided into seven experimental groups ( = 8): group I: normal control, group II: L-CA, group III: Olm, group IV: DOX. The other three groups were treated with Olm (10 mg/kg), L-CA (300 mg/kg), and their combination for 2 weeks after induction of cardiotoxicity by a single dose of DOX (20 mg/kg). In the results, DOX showed a significant elevation in serum troponin I, creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH) together with increased inflammation manifested by the rise of tumor necrosis factor-alpha (TNF-α), intercellular adhesion molecules-1 (ICAM-1), interleukin IL-1β (IL-1β), myeloperoxidase (MPO), nuclear factor-kappa B (NF-κB), and transforming growth factor beta (TGF-β) in cardiac tissues as well as DOX-induced oxidative stress by increasing in malondialdehyde (MDA) and decreasing in superoxide dismutase (SOD) and glutathione (GSH) in heart tissues. In addition, caspase-3 activity was boosted as indication of increased apoptosis. On the other hand, administration of L-CA and Olm attenuated the DOX-evoked disturbances in the abovementioned parameters. In addition, DOX exhibited echocardiographic changes and severe histopathological changes, which were significantly reversed by L-CA and Olm treatment. In conclusion, the present study data confirm the protective role of L-CA and Olm in DOX-induced cardiotoxicity, which may be related to its antioxidant, antiinflammatory, and antiapoptotic agents.

Al-Kishali, H. A., M. A. Abd El Fattah, W. A. Mohammad, and H. S. El-Abhar, "Cilostazol against 2,4,6-trinitrobenzene sulfonic acid-induced colitis: Effect on tight junction, inflammation, and apoptosis.", JGH open : an open access journal of gastroenterology and hepatology, vol. 3, pp. 281-289, 2019. jgh_dr_hanan_2019.pdf
Elmahmoudy, B. M., M. A. E. A. Fattah, M. F. Elyamany, and L. A. Rashed, "Pyrrolidine dithiocarbamate and saxagliptin ameliorate ulcerative colitis in rats", Asian Pacific Journal of Tropical Biomedicine, vol. 9, pp. 373-380, 2019. asianpacjtropbiomed_2019.pdf
El-Abhar, H., M. A. E. A. Fattah, W. Wadie, and D. M. El-Tanbouly, "Cilostazol disrupts TLR-4, Akt/GSK-3β/CREB, and IL-6/JAK-2/STAT-3/SOCS-3 crosstalk in a rat model of Huntington’s disease", PLoS ONE , vol. 13, issue 1932-6203, pp. e0203837, 2018. cilostazol.pdf
El-Dessouki, A. M., M. E. A. Fattah, A. S. Awad, and H. F. Zaki, "Zafirlukast and vincamine ameliorate tamoxifen-induced oxidative stress and inflammation: Role of the JNK/ERK pathway", Life Sciences, vol. 202, pp. 78-88, 2018. zafirlukast_and_vincamine.pdf
Abd-El-Fattah, M. A., N. F. Abdelakader, and H. F. Zaki, "Pyrrolidine dithiocarbamate protects against scopolamine-induced cognitive impairment in rats", European Journal of Pharmacology, vol. 723, pp. 330-338, 2014. Abstract

Alzheimer's disease (AD) is a chronic neurodegenerative disorder that leads to disturbances of cognitive
functions. Although the primary cause of AD remains unclear, brain acetylcholine deficiency, oxidative
stress and neuroinflammation may be considered the principal pathogenic factors. The present study was
constructed to investigate the anti-amnestic effect of pyrrolidine dithiocarbamate (PDTC) on
scopolamine-induced behavioral, neurochemical and biochemical changes in rats. PDTC (50 and
100 mg/kg) and donepezil (2.5 mg/kg) were orally administered for 14 successive days. Dementia was
induced at the end of the treatment period by a single injection of scopolamine (20 mg/kg; i.p.), and
Y-maze test was conducted 30 min thereafter. Rats were then sacrificed and homogenates of cortical and
hippocampal tissues were used for the estimation of noradrenaline, dopamine, serotonin and heat shock
protein 70 contents along with acetylcholinesterase activity. In addition, certain oxidative stress markers,
pro-inflammatory and anti-inflammatory cytokines were assessed. Histological examination of cortical
and hippocampal tissues was also performed. Scopolamine resulted in memory impairment that was
coupled by alterations in the estimated neurotransmitters, heat shock protein 70, acetylcholinesterase
activity, oxidative stress as well as inflammatory biomarkers. Histological analysis revealed serious
damaging effects of scopolamine on the structure of cerebral cortex and hippocampus. Pretreatment of
rats with PDTC in both doses mitigated scopolamine-induced behavioral, biochemical, neurochemical
and histological changes in a manner comparable to donepezil. The observed anti-amnestic effect of
PDTC makes it a promising candidate for clinical trials in patients with cognitive impairment.