Kniga na apstrakti book of abstrcts

+
0,388 mmol/L, range:0,92-1,88 mmol/L).HDL-C were significantly
decreased in patients with MI (male:0.89
+
0,218 mmol/L, range:0,61-1,33 mmol/L, females:0,95
+
o,244 mmol/L,
range:0,65-1,30 mmol/L) compared to the healthy individuals (1,40
+
0,213 mmol/L, range:0,98-0,202 mmol/L) and
serum TOAS levels were decreased in all patients (males:1,23
+
0,305 mmol/L, range:0,88-1,70 mmol/L,
females:1,29
+
0,279 mmol/L, range:0,54-1,86 mmol/L), compared to the control group (1,51
+
0,136 mmol/L,
range:1,14-1,98 mmol/L).
The decreased TOAS and HDL-C levels, thus the increased TG and TC/HDL-C ratio, compared to the con-
trol group indicate that all parameters are risk factors for CHD and MI. There are no correlation between any of lipid
parameter and TOAS. Increased levels of TG and TC/HDL-C ratio and decreased levels of TOAS and HDL-C were
found in 69% of patients with MI.
Macedonian pharmaceutical bulletin 53 (1,2) 265-266 (2007)
PP - 130
265
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Vrskata pome|u lipoproteinskiot status i antioksidantniot
kapacitet kaj pacienti so koronarni srcevi zaboluvawa
R. Go{evska, M. Su|ukovi}, E. Baga{ovska 
PZU RU@A-BIOLAB Mladinski KEJ br.2 Berovo - Makedonija
PZU apteka SOFORA Kej Revolucija br.3a - Berovo- Makedonija
Poremetuvawata vo lipoproteinskiot status i deficitot {to se javuva vo antioksidativniot sis-
tem se golemi rizik faktori kaj koronarnite sr~evi zaboluvawa i infarktot na miokardot. Poka~enoto
nivo na trigliceridite i slobodnite radikali vo plazmata, kako i niskoto nivo na HDL – holesterolot,go
zgolemuvaat rizikot od koronarni sr~evi zaboluvawa i infarkt na miokardot kako kaj ma{kata, taka i
kaj `enskata populacija.
Analizirana e vrskata pome|u totalniot antioksidanten statuis ( TOAS ) i lipidnite parametri
kako rizik faktori kaj pacienti so infarkt na miokardot. 
Nivoto na vkupniot holesterol, trigliceridite (TG), HDL - holesterolot i TOAS vo serumot se
odreduvani kaj 35 ma`i i 12 `eni na vozrast od 43-70 godini,
6-18 meseci posle prele`an infarkt. Kontrolnata grupa e sostavena od 79 zdravi osobi na vozrast
oa 25-49 godini. Doka`ano e deka ima signifikantni razliki vo site parametri, odreduvani kaj pacien-
tite so infarkt i kontrolnata grupa. TG se zgolemeni kaj site bolni (ma`i: 2,1+ 0,990 mmol/L, rang: 085-
442 mmol/L, `eni: 2,16+ 0,844 mmol/L,rang:1,24-5,36mmol/L) vo sporedba so kontrolnata grupa (1,.34+0,388
mmol/L rang: 0,92-1,88 mmol/L).
HDL holesterolot e bitno namalen kaj pacientite so ifarkt na miokardot, (ma`i:0,890+0,218
mmol/L, rang 0,61-1,33 mmol/L, `eni:0,950+0,244 mmol/L, rang: 0,65-1,30 mmol/L) vo sporedba so zdravite osobi
(1,40+0,213 mmol/L rang: 0,98+0,202 mmol/L , a nivoto na TOAS vo serumot e namaleno kaj site pacienti so
prele`an infarkt (ma`i: 1,23+0,305 mmol/L rang: 0,88+1,70 mmol/L, `eni : 1,29+0,279 mmol/L, rang:0,54+1,86
mmol/L), vo sporedba so kontrolnata grupa (1,51+0,136 mmol/L rang:1,14+1,98 mmol/L).
Namalenoto nivo na TOAS i HDL holesterolot vo serumot, poka~enite TG i odnosot pome|u TG/
HDL - holesterolot kaj pacientite so prele`an infarkt, sporeden so kontrolnata grupa, indicira deka
site navedeni parametri se rizik faktori kaj koronarnite srcevi zaboluvawa i infarktot na miokar-
dot. Ne postoi korelacija me|u lipidnite parametri i TOAS. Zgolemenoto nivo na TG i TG/HDL holes-
terol odnosot, kako i namalenoto nivo na TOAS i HDL holesterolot se najdeni kaj 69% od pacientite so
prele`an infarkt na miokardot.
Macedonian pharmaceutical bulletin 53 (1,2) 265-266 (2007)
PP - 130
266
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Activity of enzymes in serum during doxorubicine single dose therapy
of malign neoplasma in rats pretreated by fullerenol C
60
(OH)
24
Rade Injac
1
, Marija Boskovic
2
, Vukosava Djordjevic-Milic
3
, Borut Strukelj
1
, Aleksandar Djordjevic
4
,
Biljana Govedarica
3
, Natasa Radic
3
, Martina Perse
5
, Anton Cerar
5
1
Faculty of Pharmacy, Institute of Pharmaceutical Biology, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia
2
Faculty of Pharmacy, Institute of Pharmacokinetics and Biopharmaceutics, University of Ljubljana, 
Askerceva 7, 1000 Ljubljana, Slovenia
3
Medical Faculty, Department of Pharmacy, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia
4
Faculty of Sciences, Department of Chemistry, University of Novi Sad, Trg Dositeja Obradovica 3, 21000 Novi Sad, Serbia
5
Institute of Pathology, Medical Experimental Centre, Medical Faculty, University of Ljubljana, Korytkova 2, Ljubljana
The anthracycline antibiotic doxorubicin (DOX) is among the most important antitumor agents. Doxorubicin
is used against different solid tumors such as breast cancer, tumors of bile duct, endometrial tissue, the esophagus
and liver, osteosarcomas, soft tissue sarcomas and non-Hodgkin’s lymphoma. However, adverse effects such as
myelosuppression and cardiotoxicity, limits the use of doxorubicin. The use of antioxidants as protectors against cell
damage by oxidative injury could be potential solution in reduction of toxicity induced by doxorubicin. Both the in
vitro and in vivo studies show that the water soluble fullerenol (Full) C
60
(OH)
24
, a polyhydroxylated derivative of
fullerene C
60
, has strong antioxidative potential. It may function as a free radical scavenger and it strongly suppress-
es cytotoxicity of doxorubicin in model system. The scope of this experiment was to investigate potential cardiopro-
tective effects of fullerenol C
60
(OH)
24
on heart after single dose of doxorubicin in rats with malign neoplasma. 
Experiments were performed on adult female Sprague Dawley rats with breast cancer (cancerogenesis was
induced chemically with 1-methyl-1-nitrosourea (MNU) 50 mg/kg i.p. on the day 65 and 115 of age), distributed in
five groups, each containing eight individuals: Group I - healthy individuals without treatment (saline 5 ml/kg),
Group II - rats with cancer without treatment (saline 5 ml/kg), Group III - rats with cancer; DOX 8 mg/kg i.p., Group
IV - rats with cancer; Full 100 mg/kg i.p. 30 min before DOX (8 mg/kg i.p.), Group V - Full 100 mg/kg i.p. Each
experiment was repeated twice and animals were sacrificed 2 days after the treatment (approximately on the day 165
of age). Results of AST, ALT, CK, LDH and 
α-HBDH measurement in serum are showing statistically significant
damage of heart and liver in different groups of rats. A mean values of AST and ALT in DOX-, DOX-FULL- and
FULL- treated rats was significantly increased comparing to control animals. Pre-treatment with Full in dose of 100
mg/kg significantly reduced CK compared with animals treated with DOX only. According to our results, Full exert-
ed protective effects on rat's heart (CK and 
α-HBDH/LDH ratio), but on the other hand acute pancreatitis (pathohis-
tological study) can raise AST levels to two to three times normal and gives secondary damage of liver (AST, ALT,
ALT/AST and 
α-HBDH/LDH ratio).
Macedonian pharmaceutical bulletin 53 (1,2) 267 (2007)
PP - 131
267
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The effect of fullerenol on antioxidative status of heart in rats 
after single dose administration of doxorubicin
Vukosava Djordjevic-Milic
1
, Viktorija Dragojevic-Simic
2
, Biljana Govedarica
1
, Natasa Radic
1
, Rade Injac
3
,
Branislava Srdjenovic
1
, A. Djordjevic
4
, V. Vasovic
5
1
Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Serbia
2
Centre for Clinical Pharmacology, Military Medical Academy, Belgrade, Serbia
3
Institute of Pharmaceutical Biology, Faculty of Pharmacy, Ljubljana, Slovenia
4
Department of Chemistry, Faculty of Sciences, Novi Sad, Serbia
5Institute for Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Serbia
INTRODUCTION: The antracycline antibiotics have one of the widest areas of use in oncology. The most
investigated mechanisms of their antineoplastic activity include: interactions of these antibiotics with DNA, inhibi-
tion of topoisomerase II and production of free radicals. However, the side effects of doxorubicin, especially car-
diotoxicity, are the limiting factor of its use in cancer therapy. 
AIM OF RESEARCH: The aim of this research was to investigate the cardiotoxic effect of doxorubicin on
the rat experimental model and to test the usage of a potential protector fullerenol C
60
(OH)
24
in combination with
doxorubicin by measuring the activity of the antioxidative enzymes from the cytosol of the heart (catalase, CAT,
gluthatione reductase, GR, gluthatione peroxidase, GSH-Px) and from the raw fraction of the homogenized sample
of the heart (TBARS, products of lipid peroxidation).
APPLIED METHODS: The experiment was carried out on Wistar male rats, which were divided into six
groups containing 8 individuals. The control group (I) received 0.9% NaCl (1 ml/kg). The second group received 10
mg/kg of doxorubicin i.v. into the tail vein. Rest of the groups (III, IV, V) received a combination of 10 mg/kg of
doxorubicin and 50 mg/kg, 100 mg/kg and 200 mg/kg of fullerenol i.p., respectively, 30 minutes before the admin-
istration of doxorubicin. The sixth group received only 100 mg/kg of fullerenol i.p. Two and fourteen days after the
treatment animals were anesthetisized, and heart samples were taken. The samples were homogenized, and the
homogenate was divided into two fractions: the raw fraction, which was used for determining the products of lipid
peroxidation and the cytosol fraction, which was used for measuring enzyme activity of CAT, GSH-Px and GR.
Enzyme activity was measured by a kinetic method using UV/VIS spectrophotometry.
RESULTS: The obtained results showed that 2 and 14 days after treatment all of the investigated markers
of oxidative damage of cardiomiocytes were significantly increased in comparison to the control group. Fullerenol
increased the antioxidant capacity of cardiomiocytes.
CONCLUSION: The results indicate the possibility of using fullerenol as a protector in the therapy with
doxorubicin. 
Macedonian pharmaceutical bulletin 53 (1,2) 268 (2007)
PP - 132
268
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HERBALNI MEDICINSKI PROIZVODI,
HRANA I ISHRANA
Sekciski vovedni predavawa  SPL 15-16
Kratki usmeni soop{tenija  SOP 6-10
Posterski prezentcii  PP 133-176
HERBAL MEDICINAL PRODUCTS,
FOOD AND NUTRITION
Section plenary lectures SPL 15-16
Short oral presentation SOP 6-10
Poster presentation PP 133-176

Anti-inflammatory plants in practical phytotherapy
Roberto Della Loggia
Faculty of Pharmacy, University of Trieste, Italy
The first role of medicinal plants is to cure illnesses. Therefore, they have to be considered as drugs, and the
same principles we use for synthetic drugs are to be considered. In other words, for medicinal plants too, quality,
safety and chiefly activity have to be proven with scientific methods: traditions and empiric experience are not enough
for a rational use of medicinal plants, and for the products obtained from them. Furthermore, the therapeutic value
of a medicinal plant comes from the substances it contains, the active principles, and in order to exert a pharmaco-
logic effect, these principles have to be administered in a sufficient quantity. Moreover, pharmacologically active
substances may provoke untoward side effects even if they are of natural origin.
In the case of medicinal plants with anti-inflammatory activity, the picture is even more complex, because
inflammation is not an illness by itself, bat it is rather a defensive response of the organism to any kind of injuries.
The most evident aspects of inflammation are the well known phenomena of reddening, heating, swelling and pain,
that are chiefly vascular phenomena allowing the defensive actions. The true defensive actions is conducted by a com-
plex cellular system based on blood white cells, regulated by a number of different mediators such as vasoactive amines
(histamine, serotonin), plasma proteases (complement system, kinin system, clotting system), arachidonic acid metabo-
lites (prostaglandins, leukotrienes, tromboxanes, substance P), Platelet Activating Factor, cytokines and chemokines
(interleukins, Tumor Necrosis Factor), nitric oxide and many others. The activity of all these mediators has to be ruled
by some nuclear factors (NF-kB) and depends from an intricate play of many feed-back systems.
For this reason in is almost impossible to evaluate the actual efficacy of a product on the basis of in vitro
experiments, each of them involves just one mediator and gives poor information on the whole picture. Much more
significant are experiments conducted in animals or, at the best, clinical data in humans.
Anti-inflammatory products can be used for their local action, that is without resorption and systemic dis-
tribution. We know various plants that contain very active anti-inflammatory principles that can be used in this way,
chiefly for acute inflammation: the flavonoids of Chamomile or the sesquiterpene lactones of Arnica are good exam-
ples. However, the interesting challenge is the treatment of chronic inflammatory diseases, that requires the admin-
istration of drugs for a long period, such as arthritis. The physician has several synthetic drugs ad disposition, such
as cortisone or non steroidal anti-inflammatory drugs (NSAID), that are very effective but after prolonged treatments
show important side effects. Therefore, natural products have been studied in order to individuate products with a
better profile of action. 
Although many papers have been published, reporting in virto anti-inflammatory activity of a large number
of plants and of pure compounds obtained from them, at present only three groups of plants seems the most prom-
ising, on the basis of animal or clinical studies.
First of all the so called “salicylic” herbal drugs, such as Salix, Filipendula and Primula. It is well known that
these plants contains salicylic derivatives that in our body are metabolized to salicylic acid, the same metabolite pro-
duced from the acethylsalicylic acid contained in Aspirin. These drugs are therefore very used in many herbal prepa-
rations for the treatment of arthritis and similar diseases. Unfortunately, the concentration of salicylic derivatives in
these plants is very low and to obtain an effective dosage expensive purification procedures have to be set up.
Good results have been obtained in animal studies with Boswellia serrata, the Indian frankincense plant: the
boswellic acids it contains are very active, but at present clinical studies confirming the experimental data are quite
lacking. On the contrary, a large number of clinical studies confirm the anti-inflammatory activity of Harpagophytum
procumbens, commonly known as Devil’s Claw. 
Macedonian pharmaceutical bulletin 53 (1,2) 270 (2007)
SPL - 15
270
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Modern Research in Pharmacognosy; Morphological, Chemical 
and Pharmacological Characterization of Herbal Drugs
Nada Kovacevic
Faculty of Pharmacy University of Belgrade, Vojvode Stepe 450, Belgrade, Republic of Serbia;
Pharmacognosy is one of the five major divisions of the pharmaceutical curriculum, represents the oldest
branch of the profession of pharmacy. This subject plays an important role as connection between pharmacology and
pharmaceutical chemistry on one hand and between pharmacy and pharmacy administration on the other. 
Nearly half of all therapeutic agents and remedies come directly from natural sources (plants, microbes or
animals) or are derived from “chemical ideas”, substances produced by living organisms. Pharmacognosy is a branch
of the pharmacy, which has its focus on that natural sources of pharmaceutical active substances. It scope is identi-
fication or authentication of crude drugs (in dried form) using macroscopic, microscopic or chemical methods. In
today’s marketplace with so many botanical and other dietary substances available over-the-counter (e.g., ephedra,
kava, ginko etc.), the science of pharmacognosy is more important than ever in order to verify and ensure the qual-
ity and safety of ingredients and herbal medicinal and dietary products.
Beside the important role of Pharmacognosy in the education of pharmacists, research in pharmacognosy is
important part of science because it can leads to: 
• new type of chemical substance;
• new type of therapeutic agents (substance or extract or herbal drug or herbal medicinal product);
• new molecular probes that can be used to study molecular/cell biology;
• better understanding of the pharmacological, ecological and biochemical roles of substances produced 
by living organisms;
• verification of traditional herbal drugs and herbal remedies;
• new forms of biotechnology;
• new methods for the analysis of drugs, toxins and different kind of herbal preparations and products. 
In this lecture, personal experience and some results of research work will be presented to represent those
scopes of research in Pharmacognosy. It will be given review of the research on endemic plants
1-6
(Achillea alexan-
dri-regis, Potentilla speciosa), rare plants
7-9
(Cachrys ferulacea, Anthemis triumffeti), plants belonging to the same
genus as well known medicinal plant
10-14
(Epimedium alpinum, Valeriana spp), well known medicinal and spice
plants
15-18
(Zea mays, Laurus nobilis). Further, idea for new analytical method for quality control of herbal drugs
19
,
as well as some experience with production anthraquinones by in vitro cultures of the plants from Rhamnaceae fam-
ily
20-25
will be given.
Macedonian pharmaceutical bulletin 53 (1,2) 271 (2007)
SPL - 16
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The Health Benefits of Tea
Svetlana Kulevanova ,Tatjana Kadifkova Panovska
Faculty of Pharmacy, University Ss. Cyril and Methodius, Skopje, Macedonia
Tea is very popular beverage in many countries. It is ranked the second most common drink worldwide, after
water. Forms of tea include green, oolong and black (depending on the level of processing), all of which originate
from the leaves of the tea plant (Camellia sinensis L., Theaceae). Because different water preparations from tea are
consumed so frequently, even small beneficial health effects of tea could have a major influence on public health. 
Most of the scientific evidence for the health benefits of tea consumption has accumulated over the past 20
years. Many of these studies focus on the polyphenols as the principal and most active health-promoting ingredients
in green tea. These substances protect lipids from oxidative degradation, have antibacterial and antiviral action, pro-
tect skin from UV damage, are anticarcinogenic and antimutagenic, and may have other beneficial physiological
effects as well. Some studies have suggested that the polyphenols in green tea may reduce the risk of cardiovascu-
lar disease and helps prevent the development of atherosclerosis and cancer. 
The main active polyphenols of tea belong to the group of flavonoids, including catechins and their deriva-
tives. The most abundant catechin in green tea is epigallocatechin-3-gallate (EGCG), which is thought to play a main
role in the green tae's anticancer and antioxidant effects. Most of the research showing the health benefits of green
tea is based on the amount of green tea typically consumed in Asian countries (about three cups per day which could
provide approximately 300 mg of polyphenols and 30-100 mg of EGCG, as well). 
The aim of the paper is to point out that the health benefits of green tea have been extensively researched in
last decade (the PubMed database contained more than 1000 studies on green tea, most of them published after year
2000). The paper represents a brief summary of some of the high points of this most current research.    
Macedonian pharmaceutical bulletin 53 (1,2) 272-273 (2007)
SOP - 6
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Pridobivki vrz zdravjeto od upotrebata na ~ajot
Svetlana Kulevanova, Tatjana Kadifkova Panovska
Farmacevtski fakultet, Univerzitet Sv. Kiril i Metodij, Skopje, Makedonija
^ajot e popularen napitok vo mnogu zemji. Se rangira na vtoro mesto na voobi~aeni napitoci {to
se koristat {irum svetot, vedna{ posle vodata. Formite na ~ajot vklu~uvaat zelen ~aj, polufermentiran
(oolong) i crn ~aj (zavisno od stepenot na prerabotkata), dobieni od rastenieto ~aj (Camellia sinensis L.,
Theaceae). Bidej}i razli~nite vodeni podgotovki od ~ajot se koristat mnogu ~esto i vooobi~eno mnogu
dolgo, duri i malite pozitivni efekti mo`at da imaat zna~ajno vlijanie vrz zdravjeto na lu|eto.
Najgolem broj nau~ni dokazi za pridobivkite vrz zdravjeto od upotrebata na ~ajot se akumulirani
vo poslednite 20 godini. Mnogu od studiite se fokusirani vrz polifenolite kako glavni i najaktivni
promotori na zdravjeto, osobeno prisutni vo zeleniot ~aj. Polifenolite gi za{tituvaat lipidite od
oksidativnata degradacija, poka`uvaat antibakteriska i antiviralna aktivnost, ja za{tituvaat ko`ata
od negativnoto UV zra~ewe, dejstvuvaat antikancerogeno i antimutageno, i imaat i drugi pozitivni fizio-
lo{ki efekti. Nekoi od ispituvawata uka`uvaat na faktot deka polifenolite na zeleniot ~aj go reduci-
raat rizikot od kardiovaskularnite zaboluvawa i pomagaat vo prevencijata na razvojot na ateroskleroza-
ta i kancerot.
Glavnite aktivni polifenoli na ~ajot pripa|aat kon grupata na flavonoidi, vklu~uvaj}i gi i
katehinite i nivnite derivati. Dominantna katehinska komponenta e epigalokatehin-3-galat (EGCG) za
koj se smeta deka igra glavna uloga vo antikancerogenoto i antioksidativnoto dejstvo na zeleniot ~aj.
Istra`uvawata poka`uvaat deka pridobivkite vrz zdravjeto se dol`at na koli~estvoto od zeleniot ~aj
{to voobi~aeno se konzumira vo aziskite zemji (okolu tri {oqi ~ajna napivka na den {to ovozmo`uva
vnesuvawe od okolu 300 mg polifenoli odnosno 30-100 mg EGCG). 
Celta na trudot e da se uka`e na faktot deka zdravstvenite aspekti od upotrebata na zeleniot ~aj
se op{irno prou~uvani vo poslednata dekada (samo PubMed bazata na podatoci sodr`i pove}e od 1000 studii
na zelen ~aj publikuvani posle 2000 godina). Vo ovoj trud se prika`ani kratki rezimea na nekolku
najzna~ajni studii napraveni vo posledno vreme.
Macedonian pharmaceutical bulletin 53 (1,2) 272-273 (2007)
SOP - 6
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