Faculty of Medicine

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Author: search.filters.author.Shikole, EmilijaLanguage: search.filters.language.English

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    The effect of Coenzyme Q10 in Cisplatin induced myelosuppression in rats
    (Macedonian Pharmaceutical Association, Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy, 2022-12)
    Shikole, Emilija
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    Kocheva, Nedica
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    Coenzyme Q10 (2,3 dimethoxy-5 methyl-6decaprenyl benzoquinone - CoQ10) is a lipid-soluble antioxidant, vitamin-like quinone commonly known as ubiquinone or vitamin CoQ10 present in all tissues and membranes in the body. CoQ10 plays an important role in the mitochondrial respiratory chain, for synthesis of adenosine triphosphate (ATP). Further, it protects the phospholipids and the proteins in the mitochondrial membrane, from lipid peroxidation (Saini, 2011). On the contrary, Cisplatin, is an antineoplastic drug that is used for treating wide spectrum of human malignancies. However, its therapeutic outcome is limited due to development of nephrotoxicity and myelosuppression. Few mechanisms are involved such as generation of free radicals, inhibition of protein synthesis and lipid peroxidation of the membranes. One of the most important targets of Cisplatin are the mitochondrias, where it reduces the amount of ATP, and consequently increases the ROS species (Choy et al., 2015). The development of new pharmacological/therapeutical approaches and using supplements that aim the same targets as the chemotherapy but in the opposite direction, becomes a game-changer recently. Several clinical studies provided evidence supporting the use of supplements in preventing of Cisplatin induced damage of the bone marrow cells (Lin et al., 2020; Sinha et al., 2015). Therefore, the aim of this study was to evaluate the influence of the supplementation with CoQ10 on the myelosuppression induced by the treatment with Cisplatin on rats.
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    THE EFFECTS OF COENZYME Q10 MICELLAR SOLUTION AND NANOLIPOSOMES ON SUPEROXIDE DISMUTASE (SOD) ACTIVITY IN CISPLATIN-INDUCED OXIDATIVE STRESS IN RATS
    (SHMSHM - AAMD, 2023)
    Shikole, Emilija
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    Introduction: CoenzymeQ10 (CoQ10) is a lipid-soluble antioxidant that plays a key role in the mitochondria respiratory chain in the synthesis of adenosine triphosphate (ATP). It combats the oxidative stress in the body via increasing endogenous cellular defense system represented by superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) activity. Cisplatin is an antineoplastic drug used for treatment of various human malignances but because of its cytotoxicity, the therapeutic outcome of this drug is limited. Namely, it causes oxidative stress in the body by reducing the levels for glutathione (GSH), SOD, GpX, CAT and GR. Therefore, the aim of this study was to evaluate the influence of the CoQ10 supplementation (in a form of micellar solution or encapsulated into nanoliposomes) on SOD activity in oxidative stress, induced by the treatment with Cisplatin on rats. Materials and methods: 90 normotensive Wistar rats (250-300 g) were included in this study. The animals were divided in 6 groups, each consisting of 15 rats. Cisplatin (5 mg/kg) and different formulations/combinations with CoQ10 (micellar solution or nanoliposomes dispersion, 10 mg/kg) were administrated i.p. After 12 days, both kidneys were removed for measuring of SOD activity in the tissue. SOD activity was determined by the autoxidation of pyrogallol spectrophotometrically at 420 nm. Statistical analysis was performed using Statistica 7.1 for Windows. Significance was determined at p<0.05 Results: CoQ10 nanoliposome treated group showed significantly increased SOD activity, compared to all other five groups. CoQ10 nanoliposome/Cisplatin treated group showed significantly increased SOD activity compared to the Cisplatin group. Additionally, CoQ10/Cisplatin group showed increased kidney SOD activity, compared to the Cisplatin group. Conclusion: According to these results, CoQ10, as a potent antioxidant and encapsulated into nanoliposomes could be one of the possible solutions to reduce the oxidative stress and nephrotoxicity caused by the cisplatin treatment as a side effect, which is a common reason for reducing or discontinuing therapy.
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    NEPHROPROTECTIV EFFECTS OF CANDESARTAN ON DIABETIC NEPHROPATHY IN RATS
    (Macedonian Association of Anatomists and Morphologists, 2023)
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    Kolovchevski, Nikola
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    Shikole, Emilija
    Diabetic nephropathy (DN) stands out as a primary contributor to end-stage kidney damage. The renin-angiotensin system (RAS) plays a pivotal role in the advancement of DN, making angiotensin receptor blockers (ARBs) particularly noteworthy due to their influence on angiotensin II in DN development. This study investigated the impact of the angiotensin receptor blocker candesartan (CAN) on rats with streptozotocin (STZ)-induced DN, characterized by albuminuria, renal hypertrophy, and mild glomerulosclerosis.DN was induced in normotensive Wistar rats through a single injection of STZ (60 mg/kg ip). STZ administration led to diabetes mellitus (DM) symptoms and DN indicators, such as poor general condition, weight loss, increased kidney weight, elevated serum creatinine levels and BUN, augmented diuresis, and notable albuminuria. These manifestations were prominent at 4 weeks, intensifying further at 8 and 12 weeks post-STZ injection. Commencing candesartan treatment (5 mg/kg BW) at the 4-week mark post-STZ injection significantly alleviated all DN symptoms, reducing serum creatinine values and BUN, albuminuria, and diuresis. Histopathological examination at 8 and 12 weeks revealed that candesartan effectively mitigated glomerulopathy progression, improved the glomerulosclerotic index, and attenuated renal histological abnormalities induced by STZ. In conclusion, candesartan treatment ameliorates STZ-induced nephropathic changes in DM rats.
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    Acute corrosive poisonings - Frequent cause for fatal outcome
    (Elsevier BV, 2018-10)
    Chibishev, Andon
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    Shikole, Emilija
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    Bozinovska, Cvetanka
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    The Gamma Gap Predicts All-Cause Mortality in Chronic Dialysis Patients
    (2021)
    Avramovski, Petar
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    Avramovska, Maja
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    Ilkovska, Biljana
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    Sotiroski, Kosta
    The gamma gap (γ-gap) represents the total serum protein concentration minus the albumin concentration. The main aim of this study was to test whether the gamma gap is a predictor of mortality and whether it is associated with other predictors of mortality in chronic hemodialysis patients (CHPs).
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    Severe mushroom poisoning in one Macedonian family
    (SAGE, 2015-09-05)
    Chibishev, Andon
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    Miletic, Milena
    BACKGROUND: Collecting and consuming wild mushrooms is a historical tradition in many European countries, including The Republic of Macedonia. This activity is predominantly performed in the period between June and October, when the weather is warm and humidity in the air and soil is at higher levels.The Amanita genus consists of 500 different species of mushrooms; among these, Amanita phaloides, Amanita virosa and Amanita verna are most commonly found in oak forests in our country. These species are highly poisonous and because they can be similar to some edible mushrooms, they have often been misidentified. Their consumption causes severe intoxication. PURPOSE: The aim of this case series report is to demonstrate a severe poisoning with Amanita mushrooms (A. verna) that occurred in 8 patients, all from 1 Macedonian family. RESULTS: We show the differences in the clinical appearance and status of these patients, the wide spectrum of symptoms as well as the treatment and outcome of this rare poisoning. One patient, an 8-month-old baby, was excluded from the study because the infant was immediately transferred to the pediatric clinic after admission to our clinic. CONCLUSIONS: Despite modern therapy, poisoning due to ingestion of Amanita mushrooms is a serious clinical and health problem that may even be potentially lethal. The most efficient way for the general public to protect itself against potential poisoning is to avoid ingesting mushrooms that may not be edible.