Ain Shams University, Faculty of PharmacyArchives of Pharmaceutical Sciences Ain Shams University2356-83805220211201Serum MicroRNA-96 As a Potential Diagnostic Marker in Breast Cancer20421121157910.21608/aps.2021.83850.1064ENSherihan G.AbdelHamidDepartment of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo 11566, EgyptHany M.AbdelAzizDepartment of Clinical Oncology, Faculty of Medicine, Ain Shams University, Cairo 11591, EgyptAmany M.KamalDepartment of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo 11566, EgyptJournal Article20210705Breast cancer is the most commonly occurring cancer in women and the fifth leading cause of global cancer mortality. MicroRNAs (miRNAs) are essential regulators in the oncogenesis process and the identification of tumor-specific circulating miRNAs could be used for early detection of cancer. We aimed to investigate the expression pattern of microRNA 96 (miR-96) and explore its diagnostic potential in breast cancer.<br /> Subjects and methods: This study comprised 30 treatment-naïve female patients diagnosed with primary breast cancer and 20 healthy volunteers as the control group. MicroRNA 96 (miR-96) expression was measured in serum samples using Reverse Transcription Quantitative polymerase chain reaction. The diagnostic value of miR-96 was analyzed with Receiver-operating characteristics (ROC) curve.<br /> Results: Our results shows that miR-96 was significantly upregulated in breast cancer cases compared to control subjects (P<0.05). MiR-96 showed a significant diagnostic clinical value with area under the curve (AUC) 0.959, 100% sensitivity and 95.2% specificity. <br /> Conclusion: The current study implies that serum miR-96 may be a valuable and promising diagnostic marker for early detection of breast cancer. Future studies are needed to investigate the potential role of miR-96 in predicting prognosis and monitoring response to treatment. Additionally, further research is required to study the feasibility of silencing miR-96 using antagomirs for the management of breast cancer.https://aps.journals.ekb.eg/article_211579_0a8712fdb11b65cded821a1489ace2fc.pdfAin Shams University, Faculty of PharmacyArchives of Pharmaceutical Sciences Ain Shams University2356-83805220211201Overview on Parkinson’s disease: pathophysiology, and experimental models21222421158010.21608/aps.2021.92639.1068ENKhalid AhmadMohamadDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt0000-0002-1443-4075Sara A.WahdanDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, EgyptReem N.ElnagaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, EgyptJournal Article20210830Parkinson's disease is a neurodegenerative disease, caused by dopaminergic neurons death, and accompanied by rigidity, resting tremor, bradykinesia, and postural instability as well. The cause of dopaminergic neurons degeneration is still unclear. Since the dopaminergic neurons couldn’t regenerate, therefore Parkinson's disease couldn’t be cured. Thus, over the past decades, significant effort has been made to explore the etiology of Parkinson's disease development and ascertainment. This review aimed to highlight the progress that has been made in understanding of Parkinson’s disease pathophysiology. The role of oxidative stress, neuroinflammation, and apoptosis in the development of PD has been discussed. It is been clearly noticed that oxidative stress, inflammation and apoptosis are working together to develop Parkinson's disease, and each of these factor affects each other. Additionally, the experimental models, and their drawbacks have been emphasized. Additionally, the mechanism of inducing Parkinson’s disease (i.e., inducing neuroinflammation and oxidative stress) by neurotoxin has been highlighted.https://aps.journals.ekb.eg/article_211580_8925d82005bbb5866eafcb25da1e2d24.pdfAin Shams University, Faculty of PharmacyArchives of Pharmaceutical Sciences Ain Shams University2356-83805220211201Production of Cellulase by Soil Isolated Streptomyces sp.22523321158110.21608/aps.2021.92280.1067ENMery S.WaheebDepartment of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt0000-0001-8437-615XWalid F.ElkhatibDepartment of Microbiology and Immunology, Faculty of Pharmacy, Galala University, New Galala city, Suez, Egypt0000-0001-5815-3200Mahmoud A.YassienDepartment of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, EgyptNadia A.HassounaDepartment of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, EgyptJournal Article20210823Cellulases have been considered as effective biocatalysts because of their diversity of applications. A total of 165 cellulase producing Streptomyces isolates were recovered from Egyptian soil samples via cultivation on carboxymethyl cellulose agar medium. The results of screening by Congo red method showed that the tested isolates revealed different levels of cellulase activity. The isolates showed high level of cellulase production (clear zones ˃ 25 mm, n= 15) were submitted for quantitative evaluation of their cellulase productivities by using dinitrosalicylic acid assay. Cellulase production of these selected isolates ranged from 146.9 to 650.5 U/L. The highest cellulase-producing isolate (S11-6) was identified at the molecular level using 16S rRNA gene sequencing. The sequence homology analysis proved its close proximity and relatedness to Streptomyces coelicoflavus strain NBRC 15399. Production improvement of cellulase was carried out by genetic manipulation using a dose of 4 Kilogray (KGy) of gamma radiation. M1 mutant showed 1.31 fold increment in cellulase production as compared to the wild type strain of S. coelicoflavus.https://aps.journals.ekb.eg/article_211581_787d92a562c92134bc638c26bd6c4616.pdfAin Shams University, Faculty of PharmacyArchives of Pharmaceutical Sciences Ain Shams University2356-83805220211201Hepatitis C virus infection: Epidemiology in Egypt, Pathophysiology and DAAs-based therapy23424821158210.21608/aps.2021.85399.1065ENHeba A.ElbadawyFaculty of Pharmacy Ain Shams UniversitySara A.WahdanDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, EgyptEbtehalEl-DemerdashDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, EgyptJournal Article20210816Hepatitis C virus (HCV) was first identified in 1989. The situation in Egypt is really dire. The prevalence of HCV genotype 4 (GT-4) is 14.7%. About 10% of the middle-aged population (ages 15 to 59) is infected with HCV. As a result, the Hepatitis C virus is considered extremely contagious. The introduction of the directly acting antiviral medications (DAAs), sofosbuvir or simeprevir, in GT-4 patients with PEGylated interferon (PEG-IFN) and ribavirin (RBV) in a 12-week regimen substantially increased sustained virological response (SVR) rates for HCV GT-4 in 2014. Daclatasvir (DCV) is the first DAA identified in the family of HCV NS5A inhibitors with antiviral activity against a variety of HCV genotypes. It is well tolerated and safe, with a low risk of drug-drug interactions and resistance. Many investigations have discovered a rapid initial viral decline followed by a gradual decline in viral RNA, demonstrating DCV's inhibitory effect on viral reproduction, assembly, and secretion. DCV is a CYP3A4 substrate as well as a substrate for P-glycoprotein (P-gp), the most common drug efflux transporter, which are both expressed in hepatocytes and enterocytes, however it is not a BCRP substrate (Breast Cancer Resistence Protein). Concomitant treatment of DCV with other medications targeting CYP3A4 or P glycoprotein may change its pharmacokinetic characteristics.https://aps.journals.ekb.eg/article_211582_00a7d256e9ebe1a3806f1cefcb6a8116.pdfAin Shams University, Faculty of PharmacyArchives of Pharmaceutical Sciences Ain Shams University2356-83805220211201Circulating miRNA 20a, miRNA 140-5p and VEGF as Predictive Biomarkers of Metastasis in Liquid Biopsy of Breast Cancer Patients24926421160310.21608/aps.2021.96822.1070ENSherihan G.AbdelHamidDepartment of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo 11566, EgyptHany M.AbdelAzizDepartment of Clinical Oncology, Faculty of Medicine, Ain Shams University, Cairo 11591, EgyptAmany M.KamalDepartment of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo 11566, EgyptJournal Article20210919Background: MicroRNAs (miRNAs) are critical modulators in breast carcinogenesis. Metastasis remains the underlying cause of breast cancer related mortality. We sought to elucidate the predictive potential of circulating miR-20a and miR-140-5p as non-invasive liquid biopsy biomarkers. <br /> Subjects and methods: The study comprised 50 breast cancer patients (25 primary non-metastatic and 25 metastatic patients), and 15 healthy controls. The expression of miR-20a, miR-140-5p was measured using qRT-PCR. Serum levels of vascular endothelial growth factor (VEGF) was determined by ELISA. The predictive value of studied markers was evaluated by Receiver-operating characteristics (ROC) curve analysis. <br /> Results: MiR-20a was significantly upregulated, miR-140-5p downregulated, together with elevated serum VEGF levels in all breast cancer patients compared to controls and in the metastatic compared to non-metastatic group (p < 0.001 for each). MiR-20a, miR-140-5p and VEGF exhibited significant predictive value for metastasis (AUC of 1 in all), with high specificity and sensitivity. MiR-20a and miR-140-5p expression was associated with lymph node involvement (p < 0.05) and correlated with VEGF levels (p < 0.0001). <br /> Conclusion: Our findings suggest that circulating miR-20a and miR-140-5p are promising non-invasive predictive biomarkers to discriminate between metastatic and locally-confined breast cancer. They may also hold a promise as targets for miRNA-based treatments.https://aps.journals.ekb.eg/article_211603_2a39857a9aa1f3fb71a4e2be69be50cc.pdfAin Shams University, Faculty of PharmacyArchives of Pharmaceutical Sciences Ain Shams University2356-83805220211201Mini review on Potency Evaluation of Rabies Vaccine preparations26527421160610.21608/aps.2021.101125.1071ENWalaa M.RashedCentral Administration of control of Biologicals and innovative products and clinical trials, Egyptian Drug Authority Dokki, Giza, Cairo, EgyptKhaled M.AboshanabDepartment of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt0000-0002-7608-850XMohammad M.AboulwafaFaculty of Pharmacy, King Salman International University, South Sinai, Ras‑Sedr, EgyptJournal Article20211025Rabies is considered one of the most harmful viral infections of warm-blooded animals still. Thousands of people are infected with it each year worldwide. It is a fatal disease unless early treatment is received before the appearance of symptoms. About, 24,000 people die due to rabies in Africa each year and the infection is mainly transmitted by dogs. Fortunately, it could be prevented through vaccination. The importance of vaccination comes from that t is the only way to limit disease mortality levels, also the same vaccine is used for pre & post-exposure to rabies, therefore, high-quality control must be applied to it to ensure its safety, efficacy, and potency. A potency test is an important tool for experiencing the actual relative strength of manufactured assembly lots of vaccines. Because of the high variability of biological products, a potency is an effective tool that assures the lot-to-lot consistency of commercial vaccines. In this review, we aimed to discuss the rabies virus and its structure, different vaccine preparations, quality control of vaccines, different methods used in potency tests for rabies vaccine preparations including in vivo and invitro methods. In conclusion, without good quality control, we couldn’t ensure consistency in vaccine manufacturing, and without replacement of old methods depending on animals, we couldn’t go with global approaches of refinement, reduction, and replacement of animals in quality control tests especially the potency test.https://aps.journals.ekb.eg/article_211606_78f9fbb1bdb2baecda97057e04005703.pdfAin Shams University, Faculty of PharmacyArchives of Pharmaceutical Sciences Ain Shams University2356-83805220211201Assessment of Antidermatophytic Activity and chemical composition of Nigerian Citrus senensis (L.) Osbeck Essential Oil against Multidrug-Resistant Pathogenic dermatophytes Isolated from Tinea capitis Samples27528721161010.21608/aps.2021.87917.1066ENHussain Y.Ungo-koreDepartment of Pharmaceutics and Pharmaceutical Microbiology, Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, Sokoto 2346, Sokoto, Nigeria0000-0001-5951-9657Ehinmidu J.OlorunmolaDepartment of Pharmaceutical Microbiology, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Kaduna 1044, NigeriaOnaolapo J.AdemolaDepartment of Pharmaceutical Microbiology, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Kaduna 1044, NigeriaOlonitola O.StephenDepartment of Microbiology, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Kaduna 1044, NigeriaJournal Article20210806Many conventional antifungal agents are becoming ineffective against resistant strains of dermatophytes and as such the use of essential oil (EO) may confer a possible panacea to fight against such multidrug-resistant dermatophytes. This study is aimed at determining the antidermatophytic activity of EO from fruit peel of Nigerian Citrus senensis (L.) Osbeck against multidrug-resistant (MDR) tinea capitis dermatophytes and possible chemical composition. The EO was reaped by hydro-distillation and the chemical composition was investigated using gas chromatography/ mass spectroscopy (GC-MS).The antidermatophytic activity was evaluated using agar diffusion method against four dermatophyte strains (Two MDR dermatophytes, one referenced strain and one susceptible).The minimum inhibitory and fungicidal concentrations (MIC/MFC) were determined by agar dilution methods. The major components were terpenes: - D-Limonene (26.64 – 63.27%), α-terpineol (2.38 – 39.36%), β-linalool (2.28 – 13.42%), Carveol (1.36 – 3.91%), Carvone (3.62 – 3.80%) and α-Farnesene (1.29-1.83 %). Other non terpenes include 2,3,4,5-Tetrahydropyridazine (0.83%). The test results revealed EO to be active against all strains.The EO subjected to boiling temperature (100 0C) had increased amount of α-terpineol, β-Linalool, Carveol, Carvone and other imaginative compounds such as 1-Octanol (Heptyl carbinols) with increased antidermatophytic activity (inhibition diameters from 16.00 ± 0.00 - 22.67 ± 0.33 mm at a dilution of 1/16). To the best of our knowleged, this is the first description of the activity of Citrus senensis (L.) Osbeck fruit EO against multidrug-resistant tinea capitis dermatophytic strains. Our study suggests that this EO could be used clinically to treat or prevent dermatophytic infections with multidrug-resistant strains.https://aps.journals.ekb.eg/article_211610_6589755878592527d71f4b9f947ebd9b.pdfAin Shams University, Faculty of PharmacyArchives of Pharmaceutical Sciences Ain Shams University2356-83805220211201Formulation and Characterization of Proniosomal Gels loaded with Levofloxacin for dermal drug Delivery.28830321161210.21608/aps.2021.109363.1077ENLina K.MohamedDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, EgyptMona M.A.AbdelmottalebDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, EgyptAhmed S.GeneidiDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, EgyptJournal Article20211204The study aim: Formulation of proniosomal gels and evaluation of their potential in dermal drug delivery of levofloxacin, an antibacterial drug used to treat complicated bacterial infections. Methods : Levofloxacin-loaded proniosomal gels were prepared using coacervation phase separation using nonionic surfactants [spans and tweens]. Different parameters of the proniosomal gels were evaluated, including particle size [PS], zeta potential [ZP], drug entrapment efficiency percentage [EE%], in vitro drug release and ex vivo permeation studies. Results: Based on the experimental results, the EE% for the prepared formulas ranged from 32.22±0.86 to 54.83±1.17 %. Comparatively to others, levofloxacin could be best encapsulated using span 20. The particle size of the proniosomes ranged from 447±204 nm to 1089±17 nm. Proniosomal gel prepared wth span 20 had the smallest vesicle size. The zeta potential range of prepared proniosomes was from 20.95±0 mV to 60.92±0.09 mV. The prepared formulations were found to have a polydispersity index ranging from 0.198±3.23 to 0.967±0.36. Almost all of the formulas displayed a linear release profile ranging from 33.028 to 97.56 percent over 4 hours. A higher level of drug deposition was observed with span 80 compared to tween 80 after 6 hours: 18.296 % versus 9.44%. The stability study showed that there was no significant change in EE%, PS, or ZP of levofloxacin proniosomal gels after 3 months of storage. Conclusion: The dermal application of the investigated proniosomal gel formulations demonstrated promising results as nanocarriers for levofloxacin.https://aps.journals.ekb.eg/article_211612_c41ab808348ace0b3fdeb6fc3bb53224.pdfAin Shams University, Faculty of PharmacyArchives of Pharmaceutical Sciences Ain Shams University2356-83805220211201High Dose Vitamin C Improves Inflammatory Markers and Clinical Outcome Of Patients With Acute Respiratory Distress Syndrome30431621161410.21608/aps.2021.94382.1069ENNada H.FarragDepartment of Clinical Pharmacy, School of Pharmacy, New Giza University, Cairo, EgyptLamia M.ElwakeelDepartment of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt0000-0003-0250-1709Ahmed M.AbdelhafeezDepartment of Chest Diseases, Faculty of Medicine, Cairo University, Cairo, EgyptMona F.SchaalanDepartment of Clinical Pharmacy, Faculty of Pharmacy, Misr International University, Cairo, EgyptJournal Article20211118Objectives: To evaluate the clinical outcome, efficacy and tolerability of high dose IV Vitamin C administration in acute respiratory distress syndrome patients.<br /> Patients and Methods: A prospective, randomized, controlled, open-label study conducted at ICU of the National Center for Allergy and Chest Diseases, Cairo, Egypt. Forty clinically and radiologically diagnosed cases of eligible ARDS patients were randomized to either, Group 1 (Control;20); received conventional ARDS management, or Group 2 (Test;20); received 10 g IV Vitamin C on two divided doses, both for 10 days. Vitamin C, Interleukin 8 (IL8) and nuclear factor erythroid 2–related factor 2 (NRf2) levels together with PaO2/FiO2 were all measured for both groups at baseline and after 10 days from study start.<br /> Results: Both groups were comparable at baseline. After 10 days of Vitamin C administration, a significant increase (P<0.001) in levels of Vitamin C, NRf2 and PaO2/FiO2 together with a significant decrease (P<0.001) in IL8 was noted in the test versus the control group. Number of patients weaned off mechanical ventilation (MV) was significantly higher in test versus control groups (15 versus 6, P=0.004, respectively). Survival and occurrence of side effects was comparable across groups. <br /> Conclusions: Administration of 10 g IV Vitamin C in 2 divided doses daily for 10 days in ARDS patients improved lung functions, pulmonary oxygenation, oxidative stress and inflammatory markers. High dose vitamin C reduced IL8 levels and facilitated weaning off MV. Vitamin C was tolerable with no significant side effects or drug interactions reported throughout the 10 days-treatmenthttps://aps.journals.ekb.eg/article_211614_cfc9750201a2d276d577499bb04cf7b2.pdfAin Shams University, Faculty of PharmacyArchives of Pharmaceutical Sciences Ain Shams University2356-83805220211201Amelioration of Endothelial Dysfunction and Inflammation in Type 2 Diabetic Patients after Black Seed Oil Supplementation.31733021161610.21608/aps.2021.108852.1074ENAmany TalaatElgarfDepartment of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, EgyptMaram M.AboromiaDepartment of Internal Medicine and Endocrinology, Faculty of Medicine, Ain Shams University, Cairo 11591, EgyptNagwa A.SabriDepartment of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, EgyptSara MahmoudShaheenDepartment of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt0000-0001-5295-6926Journal Article20211201Aim: Endothelial dysfunction is a crucial contributor to the development of vascular problems. Nigella sativa L. seed oil which is commonly known as black seed oil is an antioxidant, anti-inflammatory and hypoglycemic agent that can be considered as an attractive candidate for improving endothelial dysfunction. Our objective is to evaluate the impact of Nigella sativa seed oil on intercellular adhesion molecule-1 (ICAM-1) and high sensitivity c-reactive protein (hsCRP), as well as quality of life of type 2 diabetic patients. <br /> Methods: A prospective, randomized, placebo-controlled, double blinded study was conducted and registered in ClinicalTrials.gov (NCT03959306). Patients were randomly given either 1800 mg/day of black seed oil or placebo capsules for 12 weeks. Full clinical history, biochemical glycemic indices, lipid profile, kidney and liver functions, hsCRP, ICAM-1, as well as diabetes-39 questionnaire were assessed at baseline and end of the study.<br /> Results: After 12 weeks, the levels of hemoglobin A1C, total cholesterol, triglycerides, hsCRP and ICAM-1, as well as diabetes control domain scores decreased significantly in intervention group compared to control group. <br /> Conclusion: The administration of black seed oil over 12 weeks showed a superior efficacy over standard treatment alone in the management of type 2 diabetes mellitus and can be considered as therapeutic option for improving endothelial dysfunction.<br /> Trial registration number: NCT03959306, Trial registration date: May, 2019.https://aps.journals.ekb.eg/article_211616_a7d96e2a63735db8ea2d0a67b8a3b588.pdfAin Shams University, Faculty of PharmacyArchives of Pharmaceutical Sciences Ain Shams University2356-83805220211201Secondary Metabolites from Carica papaya, and its Biological Activities: A Comprehensive Review33135323260210.21608/aps.2021.106355.1073ENAmrAdelDepartment of Pharmacognosy, Faculty of pharmacy, Modern university for technology and information, Cairo, Egypt.0000-0002-6428-508XMohamed S.ElnaggarDepartment of Pharmacognosy &amp; Phytochemistry, Faculty of Pharmacy, Ain Shams University, Cairo, EgyptEmanAl-SayedDepartment of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt0000-0001-7869-2009Mohamed A.RabehPharmacognosy department, Faculty of pharmacy modern university for technology and informationJournal Article20211121Carica papaya L. is the most well-known species of family Caricaceae. The edible tropical plant was widely used in traditional folk medicine worldwide and known for possessing high nutritional and medicinal values in all its parts such as fruit, leaf, seed, and latex. This review provides a comprehensive literature survey of the biological activity and the isolated phytochemical compounds reported in Carica papaya. The phytochemical research reported the isolation of several classes of phytochemicals including flavonoids, alkaloids, phenolic acids, fatty acids, sterols, triterpenes, saponins, and isothiocyanates and other miscellaneous compounds. The review also focused on the wide range of biological activities reported from crude extracts and fractions of different parts used from the Carica papaya plant that can contribute in finding alternative therapeutic approaches to combat various health problems and improve the health of the people suffering from those problems. The various biological activities feature the need for further studies to explore the bioactive compounds responsible for the biological activities and their mechanism of action.https://aps.journals.ekb.eg/article_232602_240a72f311f72a92a1f283253b0c8f9f.pdfAin Shams University, Faculty of PharmacyArchives of Pharmaceutical Sciences Ain Shams University2356-83805220211201Nephroprotective Role of Combined Sitagliptin and Oleuropein in Cisplatin-Induced Acute Kidney Injury: Regulation of SDF-1α/Nrf2/ HO-1 Axis and Autophagy35437023260410.21608/aps.2021.104714.1072ENMohamedBassionyDepartment of Biochemistry, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, EgyptNesreen OOmarDepartment of Biochemistry, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, EgyptAmira MBadrDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Nadia MHamdyDepartment of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt0000-0003-2105-107XEman FSanadDepartment of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt0000-0001-5406-2029Journal Article20211107Background: Accumulating evidence proves that cisplatin, a widely used anticancer, causes acute kidney injury (AKI). Sitagliptin (Sita), a dipeptidyl peptidase-4 (DPP4) inhibitor, is a hypoglycemic agent that can promote tissue angiogenesis and cell survival. However, little is known about the nephroprotective effect of Sita in cisplatin-induced AKI especially its effect on SDF-1α, usually degraded by DPP4. Meanwhile, the olive oil component oleuropein (Ole) activates Nrf2/heme oxygenase-1 (HO-1) axis, which ultimately leads to SDF-1α activation. Herein, we studied the nephroprotective effects of combined Sita and Ole on oxidative stress and autophagy through SDF-1α/Nrf2/ HO-1 axis in cisplatin-induced AKI in rats. Methods: AKI was induced in vivo through single IP injection of cisplatin (7 mg/kg), while Sita (10 mg/kg) and Ole (16 mg/kg) were given separately and in combination for 7 days prior and 5 days after cisplatin injection. AKI was assessed through histopathological examination, measurement of serum creatinine and urea. Also, serum GLP-1, serum and kidney SDF-1α levels were measured by ELISA. LC3-II, P62, HO-1, Nrf2, and caspase-3 were investigated by western blotting. Results: Sita and Ole monotherapy and in combination accelerated kidney recovery as they suppress serum SDF-1α, serum BUN, creatinine and renal histopathological features. Each of Sita and Ole enhanced Nrf2/HO-1axis in renal tissues while only Sita enhanced renal SDF-1α. Sita and Ole monotherapy showed incompetent autophagy where the late steps of autophagy were incomplete. Combined treatment enhanced SDF-1α in kidney tissue which showed recovery through autophagy process. Conclusion: Sita and Ole show promising nephroprotective effects in cisplatin-induced AKIhttps://aps.journals.ekb.eg/article_232604_1c45dd1ad989d93a7681cce4fc473101.pdf