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Physiol Pharmacol 22 (2018) 11-18 www.phypha.ir/ppj
Original Article
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1. Institute of Pathological Physiology, Faculty of Medicine, Šafárik University, Košice, Slovak Republic
2. Institute of Medical Physiology, Faculty of Medicine, Šafárik University, Košice, Slovak Republic
Abstract Keywords:
Introduction: The aim of the present study was to evaluate the preventive effects of Type 1 diabetes mellitus;
Flavin7 in prediabetic bio-breeding diabetes prone (BB-DP) rats. BB-DP rats;
Flavin7;
Methods: Foutthy rats were divided into 2 equal groups: group C (untreated control Prevention of diabetes
group) and group F7 with Flavin7 (natural dietary supplement F7 with bioflavonoids,
st st
0.2 mg/l) in drinking water from 21 day after birth to 171 day of their life,
respectively. Blood glucose, superoxide dismutase, glutathione peroxidase, catalase, Received: 8 Jan 2018
total antioxidant capacity, glutathione, body weight, food intake, water intake and Accepted: 24 Mar 2018
urine output were determined.
*Correspondence to:
Results: The age of diabetes onset was significantly higher for group F7 compared to M. Brenišin
group C (P<0.05). The incidence of diabetes was lower in group F7 than in group C.
Blood glucose at the diabetes onset was higher in group C than in F7 group (P<0.05).
Decrease of antioxidant status parameters, at the treatment onset as well as Tel: +421-552343406
immediately after its termination showed a drop in the F7 group firstly, but increased
progressively later, until the end of the experiment.
Conclusion: F7 delayed the development of diabetes in BB-DP rats and prevented its
onset. The severity of diabetes mellitus was milder in rats treated with F7 than in Email:
control group. marek.brenisin@upjs.sk
(Lukačínová et al., 2008). However, there are has also antiinflammatory and antivirotic effects.
contradictory views in the literature that consider Therefore, the aim of the present study was to verify
antioxidants as compounds with no detectable the F7 preventative effect on autoimmune diabetes
benefits in autoimmune diabetes in NOD mice (Li et mellitus in pre-diabetic bio-breeding diabetes prone
al., 2006). To avoid the ethical and logistical (BB-DP) rats, which is very similar to human type 1
constraints resulting from the type 1 diabetes studies diabetes.
in the outbred human population exposed to chemical
and microbiological agents (triggers) accidentaly, we Materials and methods
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v/v) at a final concentration of 0.2 mg/l. variance (ANOVA) and followed by Student-Neuman-
The solution was prepared each day anew. Animals Keuls as the post hoc test. Data were considered
received drinking water (treated and untreated) ad statistically significant if P values were <0.05.
libitum. Both groups were fed the same standard diet.
st
Experiment took 150 days (until the 171 day of life of Results
experimental animals).
From the beginning to the end of the experiment food Age in the diabetes mellitus onset
and water intake as well as urine expenditure were
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Data are presented as mean±SD (n=20/group). D = diabetic, ND = non diabetic. * < 0.05 vs. the
#
corresponding subgroup of C group. P< 0.05 compared to corresponding ND subgroup.
Data are presented as mean±SD (n=20/group). *P< 0.05 compared to C group. TAC = Total
Antioxidant Capacity
urine output, differences between groups were (150 days) bioflavonoid administration on reduction of
significant (P<0.05). All the variables were higher in the incidence of diabetes mellitus (from 65% to 10%)
group C than in F7 group. Similarly, there were and delay of the onset of diabetes (from 98±9 to
significant differences between diabetic and non- 134±9 days) in BB-DP rats.
diabetic animals within groups (P<0.05). Food and Preventive administration of F7 significantly reduced
water intake, as well as urinary excretion were higher (P<0.05) gylcemia levels in diabetic BB-DP rats.
in diabetic subjects. In both F7 and C groups, the Decrease of glycemia levels was detected also in
comparison of non-diabetic and diabetic subjects has non-diabetic rats after administration of F7, although
shown statistically not significant differences. it was not significant compare to untreated non-
diabetic rats (Table 1). This fact points to finding that
Development of indicators of antioxidant status in oral consumption of F7 is one of the most effective
BB rats ways of affecting pancreatic β-cells and treating
The antioxidant status parameters were significantly diabetes. Our results showed that F7 has high
higher in the F7 group compared to C group antioxidant activities by the ability to scavenge free
(P<0.0001) especially because of differences radicals and chelate metals. Given the hypothesized
between diabetic and non-diabetic animals relation between diabetes and inflammation and the
(P<0.0001). The results are shown in Tables 3 – 7. potential for F7 to protect the body against free
radicals and other pro-oxidative compounds, it is
Discussion plausible that consumption of F7 or flavonoid-rich
dietary supplements may reduce the risk of diabetes
In this work we demonstrated the effect of long-term onset. Tables 3 to 7 confirm, that after F7 application
Flavin7 and onset of diabetes in BB-DP rats Physiol Pharmacol 22 (2018) 11-18 | 16
per os a significant increase (P<0.05) of all and molecules, either due to random mutations,
parameters assessed in this experiment occurs. New epigenetic mechanisms or lack of certain growth
concepts appeared regarding this trend, such as factors, resulting in a "gain of function" or "loss of
nutritional therapy with nutraceuticals, and function" changes of intracellular defense
phytotherapy with phytonutrients. This functional mechanisms which differ altered cells from unaltered.
foods and phytomedicines play positive roles in In the presence of a diabetes inducer and
maintaining blood glucose levels, glucose uptake and subsequent oxidative stress, metabolic
insulin secretion, as well as modulating immune reconfiguration represents a regulated response to
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function to prevent of diabetes mellitus (Vinayagam oxidative stress (Grant, 2008) and the modulation of
and Xu, 2015). this reconfiguration may be crucial for organism
Presented findings significantly confirm the protection. When assessing antioxidant stress
preventive effect of bioflavonoids on spontaneous parameters, the central position has a reduced
diabetes in BB-DP rats. Pancreatic β-cell failure is a glutathione (García-Giménez et al., 2017). Changes
major feature of both type 1 diabetes and the type 2 of individual parameters of antioxidant protection
diabetes end stage. Type 1 diabetes is induced by should always be assessed in accordance with the
pancreatic β-cell destruction due to the autoimmune overall state of the organism. Particularly important is
mechanism and the inflammatory processes. the fact that protectively used substances which
Langerhans islets are infiltrated by macrophages, modify glycemia simultaneously modulate
natural killer cells and cytotoxic T cells (In't Veld and mechanisms of antioxidant defense of the organism
Klöppel, 2016), which produce various cytokines (Khan et al., 2009).
leading to generation of ROS and oxidative stress, It will be very important to determine the dose
which is critical for β-cell destruction (Tomita, 2017). portions of the individual antidiabetogenic agents,
Cytokines, especially pro-inflammatory such as tumor especially those used in the mixture regarding the
necrosis factor-α and interleukin-1, are cytotoxic to β- effective modulation of the normal expression of the
cells and induce an inflammatory cascade leading to target cell genome. Similarly, the chemical instability
necrosis and β-cell apoptosis. of some polyphenols during storage, extraction or
From the view of pathophysiology, the destructive analysis as well as potential enzyme hydrolysis and
effects of ROS play a significant role in a transient metabolite conversion are important for identifying
burst with the formation of small amounts of cellular bioactive forms of polyphenol compounds in vivo
ROSs, leading to the modulation of some cytokines (Williamson, 2017). In addition, it should be
and hormones, including insulin-regulated signal discussed about minerals and trace elements with the
transduction pathways (Kang et al., 2008). In BB-DP possible beneficial effects of such components, which
rats, an onset of diabetes usually occurs between could be contained in natural dietary supplements.
th th
60 and 120 days of age (Mordes et al., 2001). The molecular mechanisms underlying the glucose
According to our results, the onset of diabetes metabolism in diabetes would provide new insights in
mellitus shows a strong correlation with the decrease the field of drug development, continue to fuel
of antioxidant status parameters in BB-DP rats. excitement in this area of research and buoys the
These findings support the theory that modulation of hope that future discoveries may one day yield
the antioxidant status may have a significant therapeutic benefits (Vinayagam and Xu, 2015). With
preventive effect on the occurrence of autoimmune the rapidly increasing incidence of diabetes
type diabetes not only in BB rats (Rajput and Sarkar, worldwide, there is a greater need for safe and
2017; Redan et al., 2016; Strzyga-Lach and Czeczot, effective functional biomaterials with antidiabetic
2016). Numerous data available in the literature activity and potential preventive effects against
demonstrate the preventive effect of suppressing diabetes mellitus.
oxidative stress in various pathogenic processes
(Steven et al., 2017). Conclusion
In our opinion, the underlying cause of diabetes
mellitus induction is the disruption in the expression The results of this study demonstrated the
of genes coding endogenous antioxidant enzymes hypoglycemic and antidiabetic efficacy of F7 that had
17 | Physiol Pharmacol 22 (2018) 11-18 Ništiar et al.
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