Potential Effects of Bee Honey and Propolis Against the Toxicity of Ochratoxin A in Rats

7/28/2019 Potential Effects of Bee Honey and Propolis Against the Toxicity of Ochratoxin A in Rats

1/8

311

El-Khayat et al. Bee Honey and Propolis Against the Toxicity of Ochratoxin A in Rats

Maced J Med Sci. 2009 Dec 15; 2(4):311-318.

Macedonian Journal of Medical Sciences. 2009 Dec 15; 2(4):311-318.

doi:10.3889/MJMS.1857-5773.2009.0073

Basic Science

Potential Effects of Bee Honey and Propolis Against the

Toxicity of Ochratoxin A in Rats

Zakaria El-Khayat 1, Ahmed R. Ezzat 3, Mahmoud S. Arbid2, Wafaa I. Rasheed1 and Tahany R. Elias1

1Medical Biochemistry Department, National Research Center (NRC), Tahreer Street Doki, Cairo 002, Egypt; 2Pharmacology

Department NRC, Cairo 002, Egypt; 3Zoology Department Ain Shams University, Cairo 002, Egypt

Key words:

Bee honey, propolis, ochratoxin A,

antioxidant defense system,

peroxidation, liver, kidney.

Correspondence :

Wafaa Ibrahim Rasheed, Assistant

Professor,National Research CENTER, Medical

Biochemistry, Tahreer Street Doki,

Cairo 002, Egypt

e-mail: [email protected]

Received: 31-Aug-2009

Revised: 14-Oct-2009

Accepted: 02-Nov-2009

Online first: 17-Nov-2009

Abstract

Background. In the recent years, extensive research work has been focused on the use

of natural materials as antioxidants against the toxic oxidative materials to ameliorate their toxic

and cell damaging effects.

Aim. To evaluate the antioxidant effects of bee honey and propolis against OA-induced

oxidative stress in liver and kidney in rats.

Materials and Methods. 64 albino rats divided into 8 groups, group 1 as control, groups 2- 4 received an oral dose of OA, honey and propolis respectively for four weeks, groups 5

and 6 were treated with a weekly dose of OA concomitant with a daily dose of bee honey

in group 5 and propolis in group 6, groups 7and 8 were treated with a daily dose of bee honey

in group 7 and propolis in group 8 and single weekly dose of OA then adminstrered starting

the second week of treatment. After 4 weeks, blood samples, liver and kidney tissues were

collected for the subsequent determinations.

Results. The study showed that OA exerted toxic effects on both liver and kidney tissues

manifested as elevated serum alanine aminotransferase (ALT), gamma glutamyl transferase

(GT), creatinine and cholestrol. OA also caused perturbation in liver and kidney antioxidant

system reflected as diminished reduced glutathione (GSH), oxidized glutathione (GSSG)

content and also decrease in glutathione peroxidase (GPX) and superoxide dismutase (SOD)

activity. The level of malondialdehyde (MDA) which is a lipid peroxidation product was

elevated. Bee honey (BH) and propolis (PR) ameliorated the toxic effects of OA on liver and

kidney tissues with significant reduction of mean serum levels of ALT, GT, cholesterol and

creatinine. Also BH and PR improved the reduction in the antioxidant parameters of the liver

and kidney (GSH, GSSG content and GPX , SOD activity) caused by OA administration. The

level of MDA was also significantly decreased.

Conclusion. Bee honey and propolis ameliorated OA-induced oxidative stress in the liver and

kidney through their role in scavenging free radicals and preventing lipid peroxidation.

Introduction

In the recent years, extensive research work

has been focused on the use of natural antioxidant

products against the toxic oxidative materials to

ameliorate their toxic and cell damaging effects.

Ochratoxin A (OA), which is a toxic metabolite

OPENACCESS

produced by Aspergillus Ochraceus was reported to

cause anaemia and to increase the levels of ALT, AST,

alkaline phosphatase, triglycerides, cholesterol, uric

acid and creatinine (1, 2).Khan et al., 1989 (3) have

also shown that OA enhanced lipid peroxidation.

Propolis (bee glue) is a resinous hive product


2/8


3/8

313



Homogenate preparation

The liver and kidney tissues were cut into

small pieces and homogenized in 5 ml cold buffer (0.5

g of Na2HPO

4and 0.7 g of NaH

2PO

4per

500 ml

deionized water, pH 7.4) per gram tissue, then

centrifuged at 4000 rpm for 20 minutes at 5oC, the

supernatant was used for the assay of the content of

(GSH) and (GSSG), the activity of (GPX) and (SOD)

and the level of (MDA).

Biochemical analysis

Serum creatinine was assayed according to

the method of Bartles, et al.,1972 (17) using Bio

Merieux kit, France. Serum total cholesterol was

performed according to the method of Richmond,1973

(18)using commercial kit supplied by Randox, U.S.A.

Serum alanine aminotransferase was determined

according to the method described by Reitman and

Frankel, 1957 (19) using a Bio Merieux kit, France.

Serum gamma-glutamyl transferase (-GT) was

determined by a kinetic colourimetric method according

to Nielsen et al., 1978 (20)using a kit supplied by

Sclavo Diagnostics, Italy. Reduced glutathione (GSH)

content was determined in liver and kidney according

to the method described by Ellman, 1959 (21).

Estimation of oxidized glutathione (GSSG) content in

liver and kidney was made according to the method of

Rall and Lehninger 1952 (22). Glutathione peroxidase

(GPX) activity in liver and kidney was determined using

the Ransel kit according to Kraus and Ganthen 1980

(23). Estimation of superoxide dismutase (SOD) activity

in liver and kidney was made according to the method

of Suttle, 1986 (24) using Randox Kit. Tissue

malondialdhyde (MDA) was performed according to

the method of Draper and Hadley, 1990 (25).

Statistical Analysis

Statistical analysis was performed using SPSS

program, version 9.05 and Microsoft Excel 2003. The

data was expressed as mean standard deviation

(SD). Independent samples T-test was performed to

determine the specific differences between means.

The results are considered to be significant when p

value is less than 0.05 and highly significant.

ResultsThe results of this study are presented in

Table 1 and Figures 1 - 5. Table 1 shows the effect of

Table 1: Effect of oral treatment with ocratoxin A (OA), propolis (PR), bee honey (BH) and their combinations on serumalanine aminotransferase (ALT), serum -glutamyl transferase (-GT), serum total cholestrol and serum creatinine.

Values are expressed as means SE. Numbers between parentheses indicate the percentage of change in comparison with the corresponding control value. Means within a row with a commonsuperscript are not significantly different (P > 0.05).

Figure 1: Effect of oral treatment with ochratoxin A (OA), beehoney (BH) , propolis (PR) and their combination on liver andkidney reduced glutathione (GSH) content (micromol /g tissue)in rats. Means with a common superscript are not significantlydifferent(p>0.05).


4/8

314

Basic Science

http://www.mjms.ukim.edu.mk

ochratoxin A (OA), bee honey (BH), propolis (PR), and

their combinations on serum alanine aminotransferase

(ALT), gamma-glutamyl transferase (-GT), cholesterol

and creatinine in rats after 28 days.

There were no significant differences between

the groups of rats treated with either honey or propolis

and the control group regarding these serum

parameters.

OA administration caused significant elevation

in serum ALT, -GT, cholesterol and creatinine.

Significant decrease in their mean serum levels was

observed in the groups treated with honey or propolis

either before or after OA compared to OA-treated

group, but the ameliorating effect of BH or PR

administration before OA was better than that after OA.

Nonetheless, the mean levels of all these serum

parameters did not return back to the control value.

Figures 1- 3 show the effect of oral treatment

with OA, BH, PR and their combination on liver andkidney reduced glutathione (GSH), oxidized glutathione

(GSSG), and glutathione peroxidase (GPX). It is

apparent that there was a significant decrease in the

content of GSH, GSSG and activity of GPX in the ratsFigure 2: Effect of oral treatment with ochratoxin A (OA), beehoney (BH) , propolis (PR) and their combination on liver andkidney Oxidized glutathione (GSSG) content (micromol/g tissue)in rats. Means with a common superscript are not significantlydifferent(p>0.05).

Figure 3: Effect of oral combination with ochratoxin A (OA), beehoney (BH), propolis (PR) and their combination on liver andkidney glutathione peroxidase (GPX) activity (U/g tissue) ) inrats. Means with a common superscript are not significantlydifferent (p>0.05).

Figure 4: Effect of oral treatment with ochratoxin A (OA), beehoney (BH) ), propolis (PR) and their combination on liver andkidney superoxide dismutase (SOD) activity (unit/g tissue) israts.

treated with OA compared to the control group.

Improvement was observed in the groups treated with

BH or PR either before or after OA and the change was

statistically significant, yet their levels did not reach

those of the control.

Figure 4 shows similar results as regard the

effect on liver and kidney superoxide dismutase enzyme

(SOD) but the improvement in case of treatment with

bee honey and propolis before OA was better than thatafter OA.


5/8

315



a a a a

a

c

c

d

d

dd

d

d

b

b

Figure 5 shows the effect of OA, BH, PR andtheir combination on liver and kidney lipid peroxidation

product, malondialdhyde (MDA). OA significantly

increased its mean level above that of the control.

Treatment with BH or PR either before or after OA

inhibited the OA induced increase in the MDA, although

its mean level is still higher than that of the control. Also

figures 1- 5 show that treatment with either BH or PR

alone has no significant effect on either of the studied

parameters as compared to the control group.

DiscussionOur results revealed that ochratoxin A has

toxic effects on the liver as shown by the elevated mean

serum levels of ALT and -GT. These results are in

agreement with those of Nada et al.,1996 and Richard,

2007 (1, 2).

The liver is the most sensitive organ to

preoxidative damage because it is rich in oxidizable

substances. The increment of the oxidative stress on

the cells of the liver and the consequent decrease in the

antioxidant ability of the cells result in the occurrence

of aggressive cellular damage to the liver cells withdestruction of their membranes and the release of the

enzymes into the blood stream (26, 27).

The more severe the liver damage the higher

the release of the liver enzymes (28). In our experimenta pronounced decrease in the activities of both serum

ALT and -G T was detected after oral treatment with

bee honey or propolis either before or after OA

administration. These results indicate a marked

hepatoprotection induced by both agents. This

protective effect may be due to the antioxidant effect of

both honey and propolis which was previously confirmed

(4, 29, 30).

In the current study marked increase in the

mean serum cholesterol level was found in the OA

supplemented group which may reflect the impairment

of liver function and particularly lipid metabolism (1).Significant improvement in the serum cholesterol level

in the groups of animals treated with propolis or bee

honey either before or after OA supplementation was

observed. Langseth, 2000 (31) obtained similar results

and he explained that flavonoids in the bee honey were

responsible for such effect.

In this study nephrotoxicity was manifested

by inhibition of kidney function as indicated by increased

mean serum creatinine level.OA acts essentially in the

proximal renal tubules, inhibiting the enzyme

phosphoenol-pyruvate carboxylase, which is a lipid

peroxidant, and it alters the structural and functionalrenal ability to metabolize calcium (32). Morphologically,

the kidney shows atrophy and sclerosis of the proximal

tubules. Functionally, tubular functions are reduced

(33). Our results coincides with others by Kuiper-

Goodman and Scott 1989 (34) and Marquardt et al.,

1990 (35).

Effective reduction of serum creatinine level

was noticed after administration of bee honey or

propolis. These results are probably due to the

antioxidant protective effect of propolis and honey

which could have accumulated in the cells of the

proximal convoluted tubule of the kidney where propolis

was reported to be collected and secreted (36).

Reduced glutathione (GSH) is an important

naturally occurring antioxidant and its level in a tissue

is considered a critical determinant of the threshold for

tissue injury. Our results proved OA toxic effects

similar to those of cadmium resulting in a significant

depletion of GSH in both liver and kidney cells which

might have led to their damage due to enhancing of lipid

peroxidation (37).

OA combines with iron, facilitating its

reduction. The ironOA complex produces the

Figure 5: Effect of oral treatment with ochratoxin A (OA), beehoney (BH), propolis (PR) and their combination on liver andkidney lipid peroxidation product malondialdehyde (MDA) content(m mol/g tissue) in rats. Means with a common superscript arenot significantly different (p>0.05).

Liver&kidneyMDAcontent(mol/gtissue) 2.5

2.0

1.5

1.0

0.5

3.0


6/8

316

Basic Science


extremely damaging hydroxyl radical in the presence

of NADPH cytochrome p-450 reductase system, this

radical species may be partly responsible for OA

toxicity (38, 39). Similar results were obtained for liverand kidney oxidized glutathione (GSSG) with OA

treatment. Since GSH represents the substrate of

glutathione peroxidase which catalyzes the formation

of GSSG, so if the reduced glutathione decreases, this

is likely to be followed by a decrease of oxidized

glutathione (40).

Propolis or honey treatment ameliorated this

effect in both kidney and liver but to a some extent as

the values were still lower than that of the control group.

This protective effect is probably a result of their

antioxidant and free- radical scavenging properties

which in turn help to maintain the intracellular level of

both reduced glutathione and oxidized glutathione

(41).

The present results proved significant increase

of lipid peroxidation secondary to OA administration

which is manifested by high malondialdehyde level.

MDA is an end product of lipid peroxidation and it is

considered a late biomarker of oxidative stress and

cellular damage (42). Pervious studies suggested that

the toxicity of OA may be the result of three major

effects: inhibition of ATP synthesis, inhibition of protein

synthesis and enhanced lipid peroxidation (35). Similar

results were obtained by others (39, 43) who

demonstrated that OA enhanced lipid peroxidation

when added to liver and kidney microsomes in vitro or

when administered to rats in vivo. They ascribed this

effect to an OA- stimulated NADPH-dependent and

ascorbate -dependent lipid peroxidation with iron being

an essential cofactor.

The efficiency of several ochtratoxins

(ochratoxins A, B, C, alpha and O- methyl ochratoxin

C) to enhance lipid peroxidation was also related to the

presence of a reactive phenolic hydroxyl group in these

compounds capable of complexing with transitionalmetals. Furthermore, substantial lipid peroxidation

occurs only when cellular defense mechanisms have

been weakened or overcomed by prolonged oxidative

stress (43, 44). Lipid peroxidation was greatly reduced

in the groups of rats treated with propolis or bee honey

before or after OA treatment, as manifested by

decreased MDA level.

The antioxidant effects of bee honey was

attributed to its constituents of the most important

antioxidant trace elements and to the antioxidant

activity of its flavonoid compounds. Therefore bee

honey has been suggested to be able to decrease the

nitric oxide and lipid peroxidation . Similarly propolis

was reported to decrease lipid perodxidation (45-48)

Concerning the effect of OA on the activity ofliver and kidney glutathione peroxidase (GPX) and

superoxide dismutase (SOD), significant decrease in

their activity was observed in the OA treated group

compared to the control group. The reduction in their

activity is probably due to the increase in

malondialdehyde level caused by OA (49).

The study showed significant improvement in

GPX and SOD activity after treatment with bee honey

or propolis. This improvement plays an important role

in the cellular defense against the oxidative stress of

OA (50). In case of SOD the improvement was better

when they were administered before OA. Machlin andBendich 1987 (51) explained that bee honey

constituents include the antioxidant trace elements

iron, zinc and selenium which are essential cofactors

for the enzymatic antioxidant defense system

represented by catalase, superoxide dismutase and

glutathione peroxidase.

Conclusion

OA is a concern of public health by the

consumption of contaminated food. The kidney and

liver are its main target tissues. This study provides aneasy and relatively cheap natural products (bee honey

and propolis) as natural antioxidants for protecting

against oxidative toxic effects of OA. The results

confirmed counteracting most of OA induced hepato-

and nephrotoxicity by these bee products and showed

that their administration improved the tissue specific

antioxidant enzymes, reduced lipid peroxides thus

enhance tissue antioxidant defense capacity.

References

1. Nada S, Hussein A, El-Deeb M, Arbid M. Comparativestudy on the effect of ginseng (Panax ginseng) and l-

methionine on ochratoxicosis in rats. 1996; Journal of

Union of Arab Biologists, Cairo 5 (A) Zoology: 205-213.

2. Richard JL. Some major mycotoxins and their

mycotoxicoses: An overview. Int J Food Microbiol.2007;119(1-2):3-10. doi:10.1016/

j.ijfoodmicro.2007.07.019 PMID:17719115

3. Khan S, Martin M, Bartsch H, Rahimtula AD.

Perturbation of liver microsomal calcium homeostasisby ochratoxin A. Biochem Pharmacol. 1989;38(1):67-72.

doi:10.1016/0006-2952(89)90150-0 PMID:2910308

4. Mani F, Damasceno HCR, Novelli ELB, Martins EAM,
http://dx.doi.org/10.1016/j.ijfoodmicro.2007.07.019http://dx.doi.org/10.1016/j.ijfoodmicro.2007.07.019http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=17719115&dopt=Abstracthttp://dx.doi.org/10.1016/0006-2952(89)90150-0http://dx.doi.org/10.1016/0006-2952(89)90150-0http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=2910308&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=2910308&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=17719115&dopt=Abstracthttp://dx.doi.org/10.1016/0006-2952(89)90150-0http://dx.doi.org/10.1016/j.ijfoodmicro.2007.07.019http://dx.doi.org/10.1016/j.ijfoodmicro.2007.07.019


7/8

317



Sforcin JM. Propolis effect of different concentrations,

extracts and intake period on seric biochemical variables.

J Ethnopharmacol. 2006;105(1-2):95-8. doi:10.1016/

j.jep.2005.10.011 PMID:16293383

5. Lin-Song C, Lin-Yun HO, Chen-Chin FA, et al. The

hepatoprotective and therapeutic effects of propolis

ethanol extract on chronic alcohol-induced liver injuries.

Am J Chin Med. 1997;25(3-4):325-32.PMID:9358906

6. Liu CF, Lin CH, Lin CC,et al. Protective effect of propolisethanol extract on ethanol-induced renal toxicity: an in-

vivo study. Am J Chin Med. 2005;33(5):779-86.

doi:10.1142/S0192415X05003363 PMID:16265990

7. Kedzia B, Iwaszkiewicz J, Geppert B. Pharmacological

investigations on ethanolic extract of propolis. J OculPharmacol Ther. 2007;23(1):40-5. PMID:17341149

8. Ezz El-Arab AM, Girgis SM, Hegazy EM, Abd El-Khalek

AB. Effect of dietary honey on intestinal microflora and

toxicity of mycotoxins in mice. BMC Complement Altern

Med. 2006;6:6. doi:10.1186/1472-6882-6-6PMID:16533410

9. Chow J. Probiotics and prebiotics: a brief overview. J

Ren Nutr. 2002;12(2):76-86. doi:10.1053/

jren.2002.31759 PMID:11953920

10. White JW. Composition of honey. In Honey: A

comprehensive Survey. Crane E,1979:157-170.

11. Toussoun Z, Rashed A, Hegazi AG. Honey and

propolis as management of some chronic skin ulcers.International Symposium on Apitherapy Cairo, Egypt. 8-

9th March, 1997.

12. Mohammed A, Bash M. International Symposium onApitherapy Cairo, Egypt. 8-9th March, 1997.

13.Frohlich AA, Marquardt RR, Bernatsky A. Quantitation

of ochratoxin A: use of reverse phase thin-layer

chromatography for sample cleanup followed by liquid

chromatography or direct fluorescence measurement. JAssoc Off Anal Chem. 1988;71(5):949-53.PMID:3235415

14. Schade JE, Marsh GL , Eckert JE. Diastase activity

and hydroxy-methyl-furfural in honey and their usefulness

in detecting heat alteration. Food Res. 1958;23: 446-463.

15. Hegazi AG. Propolis: An Overview. International

Symposium on Apitherapy Cairo, Egypt. 8-9th March, 1997.

16. Schermer S. In the Blood Morphology of LaboratoryAnimals, 3rd ed. Davi FA, Co: Philadelphia, 1967: pp 42-

50.

17. Bartles H, Bohmer M, Heirii C. Serum creatinine

determination without protein precipitation. Clin ChimActa. 1972;37:193-197. PMID:5022083

18. Richmond W. Total blood cholesterol. A simple

method of obtaining blood samples and determining the

total cholesterol. Ohio State Med J. 1965;61(12):1091-4.PMID:5854897

19. Reitman S, Frankel S. A colorimetric method for the

determination of serum glutamic oxalacetic and glutamic

pyruvic transaminases. Am J Clin Pathol. 1957;28(1):56-

63.PMID:13458125

20. Nielsen LG, Ash MO. Adoption of a manual kinetic

gamma-glutamyl transferase method in the clinical

laboratory. Am J Med Technol. 1978;44(4):279-85.

PMID:25583

21. Ellman GL. Tissue sulfhydryl groups. Arch BiochemBiophys. 1959;82(1):70-7. doi:10.1016/0003-

9861(59)90090-6PMID:13650640

22. Rall TW, Lehninger AL. Assay of glutathione,

glutathione disulfide and glutathione mixed disulfide in

biological samples. J Biol Chem. 1952;194(1):119-130.PMID:14927599

23. Kraus RJ , Ganthen HE. Reaction of cyanide with

glutathione peroxidase. Kraus RJ, Ganther HE. Reaction

of cyanide with glutathione peroxidase. Biochem Biophys

Res Commun. 1980;96(3):1116-22. doi:10.1016/0006-291X(80)90067-4 PMID:7437059

24. Suttle NF. Copper deficiency in ruminants; recent

developments. Vet Rec. 1986;119(21):519-22.

PMID:3811158

25. Draper H , Hadley N. Malondialdehyde determination

as an index of lipid peroxidation. Methods Enzymol.

1990;186:421-31. doi:10.1016/0076-6879(90)86135-I

PMID:2233309

26. Sallie R, Tredger JM, Willaim R. Drugs and the liver.

Biopharmaceutics and Drug Disposition. 1991;12: 251-

259. doi:10.1002/bdd.2510120403

27. Chiarello PG, Iglesias AC, Zucoloto S, Moreno F,

Jordao AA Jr, Vannucchi H. Effect of a necrogenic dose of

diethylnitrosamine on vitamin E-deficient and vitamin E-

supplemented rats. Food Chem Toxicol. 1998;36(11):929-

35.doi:10.1016/S0278-6915(98)00043-X PMID:9771554

28. Rowland M, Tozer TN. In Clinical Pharmacokinetics:

Concepts and Applications, 3 rd ed. Lea, Febiger:

Philadelphia, 1989:148-160.

29. Gheldof N , Engeseth NJ. Antioxidant capacity ofhoney from various floral sources based on thedetermination of oxygen radical absorbance capacity and

inhibition of lipoprotein oxidation in human serum

samples. J Agric Food Chem. 2002;50(10):3050-5.

doi:10.1021/jf0114637 PMID:11982440

30. Almaraz-Abarca N, Campos MG , Avila-Reyes JA.Antioxidant activity of polyphenolic extract of monofloral

honeybee-collected pollen from mesquite. Journal of

Food Composition and Analysis. 2007;20:119-124.

doi:10.1016/j.jfca.2006.08.001

31. Langseth L. Antioxidant and the prevention of cancer.

In: Oxidants, antioxidants, and disease prevention. ILSIEurope Concise Monographs. ILSI press: Belgium,
http://dx.doi.org/10.1016/j.jep.2005.10.011http://dx.doi.org/10.1016/j.jep.2005.10.011http://dx.doi.org/10.1016/j.jep.2005.10.011http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=16293383&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=9358906&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=9358906&dopt=Abstracthttp://dx.doi.org/10.1142/S0192415X05003363http://dx.doi.org/10.1142/S0192415X05003363http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=16265990&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=17341149&dopt=Abstracthttp://dx.doi.org/10.1186/1472-6882-6-6http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=16533410&dopt=Abstracthttp://dx.doi.org/10.1053/jren.2002.31759http://dx.doi.org/10.1053/jren.2002.31759http://dx.doi.org/10.1053/jren.2002.31759http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=11953920&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=3235415&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=3235415&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=5022083&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=5854897&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=13458125&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=13458125&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=25583&dopt=Abstracthttp://dx.doi.org/10.1016/0003-9861(59)90090-6http://dx.doi.org/10.1016/0003-9861(59)90090-6http://dx.doi.org/10.1016/0003-9861(59)90090-6http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=13650640&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=14927599&dopt=Abstracthttp://dx.doi.org/10.1016/0006-291X(80)90067-4http://dx.doi.org/10.1016/0006-291X(80)90067-4http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=7437059&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=3811158&dopt=Abstracthttp://dx.doi.org/10.1016/0076-6879(90)86135-Ihttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=2233309&dopt=Abstracthttp://dx.doi.org/10.1002/bdd.2510120403http://dx.doi.org/10.1016/S0278-6915(98)00043-Xhttp://dx.doi.org/10.1016/S0278-6915(98)00043-Xhttp://dx.doi.org/10.1016/S0278-6915(98)00043-Xhttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=9771554&dopt=Abstracthttp://dx.doi.org/10.1021/jf0114637http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=11982440&dopt=Abstracthttp://dx.doi.org/10.1016/j.jfca.2006.08.001http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=5854897&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=5022083&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=11982440&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=3235415&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=9771554&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=2233309&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=3811158&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=11953920&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=7437059&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=16533410&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=14927599&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=17341149&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=16265990&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=13650640&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=25583&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=9358906&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=13458125&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=16293383&dopt=Abstracthttp://dx.doi.org/10.1016/j.jfca.2006.08.001http://dx.doi.org/10.1021/jf0114637http://dx.doi.org/10.1016/S0278-6915(98)00043-Xhttp://dx.doi.org/10.1002/bdd.2510120403http://dx.doi.org/10.1016/0076-6879(90)86135-Ihttp://dx.doi.org/10.1016/0006-291X(80)90067-4http://dx.doi.org/10.1016/0006-291X(80)90067-4http://dx.doi.org/10.1016/0003-9861(59)90090-6http://dx.doi.org/10.1016/0003-9861(59)90090-6http://dx.doi.org/10.1053/jren.2002.31759http://dx.doi.org/10.1053/jren.2002.31759http://dx.doi.org/10.1186/1472-6882-6-6http://dx.doi.org/10.1142/S0192415X05003363http://dx.doi.org/10.1016/j.jep.2005.10.011http://dx.doi.org/10.1016/j.jep.2005.10.011


8/8

318

Basic Science


2000:pp.7- 20.

32. Betina V. Mycotoxins-chemical, biological and

environmental aspects. Amsterdan (NL): Elsevier,

1989;325-421.

33. Pitt TL. Toxigenic fungi: which are important? Med

Mycol. 2000;38 Suppl 1:17-22.PMID:11204142

34. Kuiper-Goodman T, Scott PM. Risk assessment ofthe mycotoxin ochratoxin A. Biomed Environ Sci.

1989;2(3):179-248. PMID:2692617

35. Marquardt RR, Frohlich A, Abramson D. Ochratoxin

A: An important western canadian storage mycotoxin. Can

J Physiol Pharmacol. 1990;68(7):991-9.PMID:2200593

36. Sun F, Hayami S, Haruna S. et al. Vivo antioxidative

activity of propolis evaluated by the interaction with

vitamins C and E and the level of lipid hydroperoxides inrats. J Agric Food Chem. 2000;48(5):1462-5.doi:10.1021/jf990594t PMID:10820043

37. Demopoulos HE. Control of free radicals in biologic

systems. Fed Proc. 1973;32(8):1903-8. PMID:4718907

38. Hasinoff BB, Rahimtula AD , Omar RA. NADPH-

cytochrome-P-450. Reductase promoted radical

production by the iron (III)-ochratoxin A complex. Biochim

Biophys Acta. 1990;1036(1):78-81.PMID:2171659

39. Omar RF, Hasinoff BB, Mejilla F, Rahimtula AD.

Mechanism of ochratoxin A stimulated lipid peroxidation.

Biochem Pharmacol. 1990;40(6):1183-91. doi:10.1016/

0006-2952(90)90382-U PMID:2119584

40. Palomero J, Galan AI, Munoz ME.et al. Effects ofaging on the susceptibility to the toxic effects of cyclosporin

A in rats. Changes in liver glutathione and antioxidant

enzymes. J Free Radic Biol Med. 2001;30:836 -845.

doi:10.1016/S0891-5849(01)00471-3

41. Mahran LG, El-Khatib AS, Agha AM, Khayyal MT. Theprotective effect of aqueous propolis extract on isolated

rat hepatocytes against carbon tetrachloride toxicity. Drugs

Exp Clin Res. 1996;22(6):309-16.PMID:9034757

42. Abdel-Wahhab MA, Abdel-Galil MM, El-Lithey

M.Melatonin counteracts oxidative stress in rats fed anochratoxin A contaminated diet. J Pineal Res.

2005;38:130-135. doi:10.1111/j.1600-

079X.2004.00184.x

43. Rahimtula AD, Bereziat JC, Bussacchini-Griot V,

Bartsh H. Lipid peroxidation as a possible cause ofochratoxin A toxicity. Biochemical Pharmacology.

1988;37:4469- 4477. doi:10.1016/0006-2952(88)90662-

4

44. Halliwell BC , Gutteridge JMC. Oxygen toxicity, oxygen

radicals, transition metals and disease. Biochemical J.1984;219(1):1-14. PMID:6326753

45. Rosenblat G, Angonnet S, Goroshit A. et al. Antioxidant

properties of honey produced by bees fed with medical

plant extracts. Bee-products: properties-applications, and

apitherapy. 1997;49:49- 55.

46. El-Khayat Z, Hamdy H. Antitumor efficacy of ediblePortulaca oleracea and bees honey in mice inoculated

with Ehrlich Ascites tumor cells. Journal Union Arab

Biology. 2000;13A:583-600.

47. Atrooz OM, Al-Sabayleh MA, Al-Abbadi SY. Studies on

physical and chemical analysis of various honey samples

and their antioxidant activities. J Biol Sci. 2008;8:1338-

1342. doi:10.3923/jbs.2008.1338.1342

48 .Bhadauria M , Nirala SK ,Shukla S. Multiple treatment

of propolis extract ameliorates carbon tetrachloride

induced liver injury in rats. Food Chem Toxicol.

2008;46(8):2703-12. doi:10.1016/j.fct.2008.04.025

PMID:18572298

49. Meki AR , Hussein AA. Melatonin reduces oxidative

stress induced by ochratoxin A in rat liver and kidney. Comp

Biochem Physiol C Toxicol Pharmacol. 2001;130(3):305-

13 . doi:10.1016/S1532-0456(01)00248-4

PMID:11701387

50. Lee MK, Yeo H, Kim J , Kim YC. Protection of rat

hepatocytes exposed to CCL4 in-vitro by cynandione A, a

biacetophenone from Cynanchum wilfordii. J Pharm

Pharmacol. 1955;7(5):341-5. PMID:14368529

51. Machlin IK, Bendich A. Free radical tissue damage:

protective role of antioxidant nutrients. Free Radic Biol

Med. 1987;6:441-445.
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=11204142&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=11204142&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=2692617&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=2200593&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=2200593&dopt=Abstracthttp://dx.doi.org/10.1021/jf990594thttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=10820043&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=4718907&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=2171659&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=2171659&dopt=Abstracthttp://dx.doi.org/10.1016/0006-2952(90)90382-Uhttp://dx.doi.org/10.1016/0006-2952(90)90382-Uhttp://dx.doi.org/10.1016/0006-2952(90)90382-Uhttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=2119584&dopt=Abstracthttp://dx.doi.org/10.1016/S0891-5849(01)00471-3http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=9034757&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=9034757&dopt=Abstracthttp://dx.doi.org/10.1111/j.1600-079X.2004.00184.xhttp://dx.doi.org/10.1111/j.1600-079X.2004.00184.xhttp://dx.doi.org/10.1016/0006-2952(88)90662-4http://dx.doi.org/10.1016/0006-2952(88)90662-4http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=6326753&dopt=Abstracthttp://dx.doi.org/10.3923/jbs.2008.1338.1342http://dx.doi.org/10.3923/jbs.2008.1338.1342http://dx.doi.org/10.1016/j.fct.2008.04.025http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=18572298&dopt=Abstracthttp://dx.doi.org/10.1016/S1532-0456(01)00248-4http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=11701387&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=14368529&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=9034757&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=14368529&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=11701387&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=2119584&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=18572298&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=2171659&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=4718907&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=10820043&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=2200593&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=6326753&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=2692617&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=11204142&dopt=Abstracthttp://dx.doi.org/10.1016/S1532-0456(01)00248-4http://dx.doi.org/10.1016/j.fct.2008.04.025http://dx.doi.org/10.3923/jbs.2008.1338.1342http://dx.doi.org/10.1016/0006-2952(88)90662-4http://dx.doi.org/10.1016/0006-2952(88)90662-4http://dx.doi.org/10.1111/j.1600-079X.2004.00184.xhttp://dx.doi.org/10.1111/j.1600-079X.2004.00184.xhttp://dx.doi.org/10.1016/S0891-5849(01)00471-3http://dx.doi.org/10.1016/0006-2952(90)90382-Uhttp://dx.doi.org/10.1016/0006-2952(90)90382-Uhttp://dx.doi.org/10.1021/jf990594t

Documents

Potential Effects of Bee Honey and Propolis Against the Toxicity of Ochratoxin A in Rats