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2100
Advances in Environmental Biology, 7(9): 2100-2104, 2013
ISSN 1995-0756
This is a refereed journal and all articles are professionally screened and reviewed
ORIGINAL ARTICLE
Inhibitory Effects of Cinnamon Extract on Gentamicin-Induced Nephrotoxicity in Mail
Adult Wistar Rats
Sedigheh Tanomand, Mahmood Najafian
Department of Biology, Jahrom Branch, Islamic Azad University, Jahrom, Iran
Sedigheh Tanomand, Mahmood Najafian: Inhibitory Effects of Cinnamon Extract on GentamicinInduced Nephrotoxicity in Mail Adult Wistar Rats
ABSTRACT
Introduction: Among the factors that can cause kidney failure are taking medications with amino
glycosides, especially gentamicin toxicity has special importance. Studies have shown that gentamicin will
exercise their nephrotoxicity by virtue of Create free radicals. Cinnamon has antioxidant properties. In this
study, the antioxidant properties of cinnamon reducing effect of gentamicin-induced nephrotoxicity were
studied. Material and methods: 42 mail adalt wistar rats were randomly divided into 7 groups. Group C was
given no medication. S group, the saline solution was injected intraperitoneally. Group Ci200 extract of
cinnamon (200mg/kg B.W), Group G100 gentamicin (100mg/kg B.W), and Groups GCi50, GCi100 and
GCi200 order gentamicin with the dosages of 50, 100 and 200 mg per kg body weight of ethanol extracts of
cinnamon in the injections. During the experimental period was 28 days. Later samples were taken at the end of
day 28, rats were killed and blood urea nitrogen, uric acid and creatinine levels were measured. Results: The
levels of blood urea nitrogen (BUN) has shown a significant increase in group G100 compared to group C (p
<0.05). In Groups GCi50, GCi100 and GCi200, roughly proportional to the dose of cinnamon, blood urea
nitrogen levels have been reduced. Creatinine concentration showed a significant increase in G100 than group C
(p <0.05) and a significant reduction of GCi200 compared to G100 (p <0.05). Concentration of uric acid in the
G100 group showed a significant increase compared to the C group. GCi200 and GCi100 groups showed a
significant reduction compared to the group G100 (p<0.05). Discussion and Conclusion: Cinnamon bark extract
is able to protect against the nephrotoxicity induced by gentamicin. The protective effect maybe dependent to
anti oxidant properties of cinnamon extract.
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Key words: Gentamicin, Cinnamon, Rats, Nephrotoxicity.
Introduction
Antibiotics are the most widely used drugs.
These drugs can prevent many problems caused by
Infections. However, antibiotics can have side effects
and damage various body organs, including the liver,
kidney, brain, blood, skin, eyes, mouth and other. [1]
In particular amino glycoside antibiotic gentamicin is
widely used to treat severe infections Gram-negative
bacteria. [2] Despite its clinical efficacy, the clinical
use of gentamicin is limited due to side effects of
drug. Nephrotoxicity is important side effects of
drugs that are responsible for acute renal failure in a
significant number of people are taking this
medication. Given that one of the major side effects
of gentamicin is creating nephrotoxicity, the using
drug is faced with restrictions [3-5[. Increased
production of reactive oxygen species (ROS), which
can be seen after the use of gentamicin in cells, is
effective on the induction of toxic effects of this drug
on kidney structure and function [ 6-8].
Some studies have reported that oxidative stress
plays a role in gentamicin-induced nephrotoxicity
[9]. Gentamicin increased Superoxide anion
production, hydrogen peroxide and hydroxyl radicals
by kidney mitochondria [10]. Free radicals cause
peroxidation of membrane phospholipids, protein
denaturation and DNA chain break. Most significant
biological damage by reactive oxygen metabolites
are reaction with unsaturated lipid peroxidation and
thus their peroxidation. This effect caused changes in
membrane fluidity and finally membrane molecules
are permeable to even as large as enzymes. [11].
Cinnamon plant with the scientific name
Cinnamomum zeylanicum (C. Verum), and the
generic name is Cinnamon. This evergreen tree
family belongs to smells leaf (Lauraceae) and is
native to Sri Lanka and southeast India. Cinnamon is
used as flavoring pastries and foods and used for
pharmaceutical and medical applications as well.
This plant is one of the oldest medicinal plants used
in traditional medicine as an important drug.
Different parts of this plant has many health benefits,
Corresponding Author
Mahmood Najafian, Department of Biology, Jahrom Branch, Islamic Azad University, Jahrom, Iran
E-mail: [email protected]
2101
Adv. Environ. Biol., 7(9): 2100-2104, 2013
including the skin, so that its use strengthens the
heart, stomach and intestines, improving kidney
function and increase sexual power [12]. Medicinal
value of this plant is due to its volatile oil. The main
components of this oil include cinnamaldehyde,
eugenol and safrol with insulin-like activity and can
be useful in the treatment of diabetes [13]. These
combinations are involved in decreasing in
triglycerides, and LDL cholesterol levels [14].
Cinnamon has anti-bacterial and anti-fungal
properties [15]. Cinnamon in wound healing, it is
also used to treat nausea and diarrhea [15-16]. In this
study, the antioxidant properties of cinnamon reduce
nephrotoxicity gentamicin-induced was studied.
Material And Methods
This study experimentally and is completely
random. All animal experiments in this study comply
with the code of conduct has been developed. 42
adult Wistar rats weighing 200±10 g and 75 days of
age, was produced from Shiraz Razi Vaccine &
Serum Research Center. The rats were housed in
Islamic Azad University Jahrom Branch Animal
House for 28 days under laboratory conditions
include a temperature of 21±2° C and 12 h light and
12 h dark cycle was used. The mice were kept in
cages; metal mesh doors and a standard rodent diet
(pellete) were used. Glass bottles of water were also
provided. Their food and water were free. Cage 3
times a week it was disinfected with 70% alcohol.
Caspian to 100 mg in 2 mL ampules were bought
from Gentamicin Pharmaceutical companies.
Gentamicin dose of 100 mg per kg body weight in
rats (100mg/kg Bw) was performed. Cinnamon
extract for cinnamon peel powder using a mill and 24
g of powder was dissolved in 96% ethanol 200cc.
The mixture was kept at room temperature for 24
hours. The mixture using a magnetic stirrer (Shaker)
was mixed for 4 minutes and was flat on Whatman
paper. Paper and powder residue on it in the oven set
temperature of 50 ° C for 1.5 hour were dried. The
powder was dissolved in saline and given weight in
rats at doses 50, 100 and 200mg/kg-BW prepared.
Samples (cinnamon extract, gentamicin and
saline solution) with 0.2ml insulin syringe volume
were injected intraperitoneally at 9 am each day.
42 rats were divided randomly into 7 groups as
follows:
Group C: were maintained on normal without
any medication.
Group S: Rats in this group recevied saline
solution as solvent of cinnamon extract and
gentamicin.
Group Ci200: Rats in this group recevied
cinnamon extract 200mg/kg B.W.
Group G100: Rats in this group recevied
gentamicin 100mg/kg B.W.
Group GCi50: Rats in this group recevied
Gentamicin 100mg/kg B.W with cinnamon extract
50mg/kg B.W.
Group GCi100: Rats in this group recevied
gentamicin 100mg/kg B.W with cinnamon extract
100mg/kg B.W.
Group GCi200: Rats in this group recevied
gentamicin 100mg/kg B.W with cinnamon extract
200mg/kg B.W.
After 28 days, rats of all groups were comatose
after weighing by Ether and the heart by syringe, 5
ml blood was measured after separating the serum
concentration of urea nitrogen, uric acid and
creatinine were measured in serum. To express the
results, compare the amount and distribution of
column charts are used to express the values are
given as Mean ± SD. One way analysis of variance
(ANOVA) followed by Tukey’s post hoc test for
multiple comparisons were used to compare
difference between experimental groups. The
criterion for statistical significant was P<0.05. For all
data analysis software SPSS version 18.0 statistical
doing tests were used.
Results:
The results showed that the concentration of
blood urea nitrogen (BUN) in groups G100, GCi50
and GCi100 is a significant increase compared to the
C group. BUN concentration in groups GCi50,
GCi100 and GCi200 compared to G100 were
reduced with a dose dependent manner pattern.
(P<0.05).
As shown in figure 2, serum creatinine
concentrations were significantly increased in G100
and GCi50 groups compared to C group. The
GCi200 group was significantly decreased compared
to G100 and GCi50 (P<0.05).
The results show that the serum uric acid
concentration was significantly increased in G100
group compared to the C group. The group GCi50 is
a significant deccrease compared to G100 group. In
GCi100 and GCi200 is a significant reduction
compared to G100 and GCi50 (P<0.05).
2102
Adv. Environ. Biol., 7(9): 2100-2104, 2013
Fig. 1: Effect of gentamicin and cinnamon extract on BUN. The culmnes that have at least one common letter,
have not significant different from each other at the level of P<0.05.
1.2
b
Creatinine(mg/dl)
1
0.8
b
a
a
a
ab
a
0.6
0.4
0.2
0
C
S
Ci200
G100
GCi50
Experimental groups
GCi100
GCi200
Fig. 2: Effect of Gentamycine and cinnamon extract on creatinine. The culmnes that have at least one common
letter, have not significant different from each other at the level of P <0.05.
Fig. 3: Effect of Gentamycine and cinnamon extract on uric acid. The culmnes that have at least one common
letter, have not significant different from each other at the level of P <0.05.
2103
Adv. Environ. Biol., 7(9): 2100-2104, 2013
Discussion:
Antibiotics such as gentamicin have high
consumption. This medication is used to treat
infections of Gram-negative bacteria in humans and
animals, the effects of gentamicin are renal toxicity
(nephrotoxicity) [2-3]. Body toxins, such as urea,
uric acid, creatinine and bilirubin metabolites are
excreted through the kidneys. Since the kidney is a
major problem in today's society, so pay careful
attention to the structure and function, it can be
important for the health of the individual [17]. The
results of this study indicate that gentamicin has a
significant effect on serum BUN, uric acid and
creatinine. This expression is induced nephrotoxicity
induced by gentamicin [18]. BUN levels were
significantly increased in group G100 compared to
group C (P <0.05), indicating the gentamicin-induced
renal failure [18]. Groups GCi50, GCi100 and the
GCi200, there was significant dose-dependent
decrease in BUN levels and this indicates the
positive effect of cinnamon on gentamicin-induced
nephrotoxicity. Serum creatinine was significantly
increased in group G100 compared to group C (P
<0.05) that this is in line with gentamicin-induced
renal injury [19]. In GCi200 group, serum creatinine
has a significan decrease compared to a G100. This
expression is a gentamicin-induced nephrotoxicity
antioxidant effect of cinnamon in reducing
complications. Serum uric acid in group G100
receiving gentamicin G100 was a significant increase
in the gentamicin-induced renal injury [18]. Uric asid
has a significant decrease in groups which receive
gentamicin and cinnamon compared to groups which
receive just gentamicin and this indicates cinnamon,
as Antioxidants, can decrease side effects induced
from gentamicin[20].
Antioxidants combined with gentamicin
gentamicin-induced tissue damage has been slightly
reduced in the kidneys [21-23]. Studies indicate the
presence of antioxidant compounds in cinnamon
[24]. Researchers know antioxidant effect of
cinnamon more related to eugenol and methyl
hydroxyl chalcone. Oral administration of a eugenol
cause normal activity of glutathione peroxidase and
glutathione in cells is increased [25]. Due to the
adverse effects of free radicals and oxidative stress
responses, antioxidant compounds that can protect
the body from damage caused by oxidative stress
may be necessary. Antioxidants play a special role in
the prevention and treatment of diseases [26-27]. See
generally, indicates damage in groups received
Gentamicin and extract simultaneously, compared to
the group receiving gentamicin alone which observed
renal decline indicating the positive effects of
cinnamon extract.
Conclusion:
Due to above, using cinnamon is effective in
decreasing Blood urea nitrogen, serum creatinine and
uric acid gentamicin – induced. So that further
improvements can be seen at higher doses. Due to
the low cost of Cinnamon, ease of use and minimal
side effects seem to be less gentamicin as an adjuvant
treatment in order to minimize damage to the kidney.
References
1.
Ayatollahi, J., 2005. Evaluation of knowledge
and activities of medical students in the last two
years of their education about chemoprophylaxis
following contact with infectious diseases.
IJCID., 9(26): 54-9.
2. Salgado, C.M., F.L. Hernandes, J.M. Novoa,
2007. Glomerular nephrotoxicity of amino
nucleosides.
Toxicology
and
applied
pharmacology, 223: 86-98.
3. Farombi Eo, M. Ekor, 2006. Curcumin
attenuates gentamicin induced renal oxidative
damage in rats. Food and chemical Toxicology,
44: 1443-1448.
4. Karahan, I., A. Atessahin, S. Yilmaz, A.O.
Cerbisat, F. Sakin, 2005. Protective effect of
lycopene in induced oxidative stress and
nephrotoxicity in rats. Toxicology, 215: 198204.
5. Kumar, J.V., M.U. Naidu, A. Anwar, K.S.
Ratnakar, 2000. Probucol protects against
gentamicin induced nephrotoxicocity in rats.
Indian J Pharmacol., 32: 108-113.
6. Anees, A.B., F. Neelam, 2008. Shubha.Time
dependent effects of gentamicin on the enzymes
of carbohydrate metabolism brush border
membrane and oxidative stress in rat kidney
tissues. Life sci, 82: 450-459.
7. Kadkhodaee, M., H. Khastar, H.A. Arab, R.
Ghaznavi, M. Zahmatkesh, M. Mahdavi, 2007.
Antioxidant vitamins preserve superoxide
dismutase activities in gentamicin induced
nephrotoxicity.Transplant Proceed., 39: 864865.
8. Pedraza, J., A. Gonzalez, D. Maldonado, D.
Barrera, O. Medina, R. Hernandez, 2003.
Disulfide
ameliorates
gentamicin-induced
oxidative stress and nephropathy in rats. Eur J
Pharmacol., 18: 71-8.
9. Cuzzocrea, S., E. Mazzon, L. Dugo, I. Serraino,
R. Paola, D. Britti, 2002. A role for superoxide
in gentamicinmediated nephropathy in rats. Eur j
pharmacol., 450: 67-76.
10. Yang, C., X. Du, Y. Han, 1995. Renal cortical
mitochondria are the source of oxygen free
radicals enhanced by gentamicin. Ren Fail., 17:
21-26.
11. Inoue, S., S. Kawanishi, 1995. Oxidative DNA
damage induced by simultaneous generation of
nitric-oxide and superoxide. FEBS lett., 371:
86-88.
2104
Adv. Environ. Biol., 7(9): 2100-2104, 2013
12. Shah, A.H., A.H. AL-Shareef, A.M. Ageel, S.
Qureshi, 1998. Toxicity studies in mice of
common spices Cinnamomum zeylanicum bark
and piper lonum fruits. Plant Food for Human
Nutrition., 52: 231-239.
13. Anderson, R.A., C.L. Broadburst, M.M.
Polansky, W.F. Schmidt, A. Khan, V.P.
Flanagan, N.W. Schoene, D.J. Raves, 2004.
Isolation and characterization of polyphenol
type- A polymers from cinnamon with Insulinlike biological activity. Journal of Agricultural
and Food Chemistry, 52(1): 65-70.
14. Khan, A., M. Sfdar, M.M. Ali Khan, K.N.
Khattak and R.A. Anderson, 2003. Cinnamon
improves glucose and lipids of people with type
2 diabetes. Diabetes Care, 26(12): 3215-3218.
15. Nir, Y., I. Potasman, E. Stermer, M. Tabak, I.
Neeman, 2000. Controlled trial of the effect of
cinnamon extract on Helicobacter pylori.
Helicobacter., 5(2): 94-97.
16. Kamath, J.V., A.C. Rana, A.R. Chowdhury
2003. Pro-healing effect of Cinnamomum
zeylanicum bark. Phytotherapy Research, 18(8):
970-972.
17. Rumiza, A.R., O. Khairul, I.I. Mohd, Z.
Rajamuhamad,
A.H.
Rogayah,
2008.
Determination of malathion levels and the effect
of malathion on the growth of Chrysomya
megacephala (Fibricius) in malathion- exposed
rat carcass. Trooical biomedicine, 25(3): 184190.
18. Ihab Talat, A., A. Abdel-GHany, G. Mohamed,
2009. Protective Effect of Quercetin against
Gentamicin-Induced Nephrotoxicityin. Rats Biol
Pharm Bull., 32(1): 61-67.
19. Wedeen, R., V. Batuman, C. Cheeks, E. Maquet,
H. Sobel, 1983. Transport of gentamicin in rat
proximal tubule. Lab Invest., 48(2): 212-223.
20. Alladin, P., P. Hakan, T. Seda, C. Cemil, V.
Nigar, U. Muharrem, 2006. Protective role of
aminoguanidin on gentamicin induced acute
rena failure in rats.Acta histochemica., 108: 365371.
21. Karahan, I., A. Atessahin, S. Yilmaz, A.O.
Cerbisat, F. Sakin, 2005. Protective effect of
lycopene in induced oxidative stress and
nephrotoxicity in rats. Toxicology, 215: 198204.
22. Farombi Eo, M. Ekor, 2006. Curcumin
attenuates gentamicin induced renal oxidative
damage in rats. Food and chemical Toxicology,
44: 1443-1448.
23. Kadkhodaee, M., H. Khastar, H.A. Arab, R.
Ghaznavi, M. Zahmatkesh, M. Mahdavi, 2007.
Antioxidant vitamins preserve superoxide
dismutase activities in gentamicin induced
nephrotoxicity. Transplant Proceed, 39: 864865.
24. Onderoglu, S., S. Sozer, K. Mine Erbil, R. Ortac,
F. Lermioglu, 1999. The evolution of long-term
effects of cinnamon bark and olive leaf on
toxicity induced by streptozotocin administration
to rats. Journal of Pharmacy and Pharmacology,
51: 1305-1312.
25. Van kampen, E.J. and W.G. Zijlstra, 1985.
Determination of hemoglobin and it's
derivatives. Clinical Chemistry, 8: 1414.
26. Peng, J., G.L. Gones, K. Watson, 2000. Stress
protein as biomarkers of oxidative stress: Effects
of antioxidant supplement. Free Radic. Biol.
Med., 28: 1598-606.
27. Bjelakovic, G., D. Nikolova, L.L. Gluud, R.G.
Simonetti, C. Gluud, 2007. Mortality in
randomized trials of antioxidant supplements for
primary and secondary prevention: systematic
review and metaanalysis. JAMA., 297: 842-57.