The Protective Efficacy of Kelakai (Stenochlaena Palustris) on

Cadmium-induced Glucose Metabolism Alteration In Vitro

Eko Suhartono

1,2

, Ika Kustiyah Oktaviani

, Adenan

, Iskandar Thalib

Department of Medical Chemistry/Biochemistry, Faculty of Medicine, Lambung Mangkurat University, Ahmad Yani Street

Km, Banjarbaru, South Kalimantan, Indonesia

Center of Excellent: Research Consortium for Sustainable Tropical Forest Management, Banjarbaru, South Kalimantan,

Indonesia

Department of Anatomy Pathology, Faculty of Medicine, Lambung Mangkurat University, Banjarmasin, South

Kalimantan, Indonesia

Department of Public Health, Faculty of Medicine, Lambung Mangkurat University, Banjarmasin, South Kalimantan,

Indonesia

Department of Child Health, Faculty of Medicine, Lambung Mangkurat University, Banjarmasin, South Kalimantan,

Indonesia

Keywords: Cadmium, Glucose Metabolism, Stenochlaena palustris

Abstract: The objectives of this study were to determine the protective effect of kelakai (Stenochlaena palustris)

leaves extract on cadmium (Cd)-induced glucose metabolism alteration in vitro. The protective effect of

plant extracts extract was determined by assessing the activity of pancreas amylase and liver glucokinase,

the concentration of liver glucose, glycogen, and methylglyoxal (MG). In this present study, the liver and

pancreas samples were obtained from 32 old male Rattus novergicus. Each model then divided into 4 groups

consisting of: pancreas or liver + 0.3 mg/l CdSO

(T1); pancreas or liver + 0.3 mg/l CdSO

+ 5 mg/l leaves

extract (T2); pancreas or liver + 0.3 mg/l CdSO

+ 10 mg/l leaves extract (T3); and pancreas or liver + 0.3

mg/l CdSO

+ 15 mg/l leaves extract (T4). Results of this present study shows that the administration of S.

palustris leaves extract could significantly decreased the pancreas amylase activity, the level of liver

glucose and MG, and significantly increase the liver glucokinase activity, and the level of liver glycogen (P

< 0.05). In conclusions, the results of this present study indicated that the administration of S. palustris

leaves extract could improve the glucose metabolism alteration by Cd.

1 INTRODUCTION

Industrialization and urbanization development

have resulted in increasing of environment

contamination by several toxic substances, including

heavy metal (Anyakora et al., 2013). Among heavy

metals, cadmium (Cd) is one of the heavy metal that

is very toxic to human body even at low

concentration (Rahman et al., 2014). If Cd enters the

human body, it could irreversibely accumulates and

affect some vitals organs such as liver, pancreas,

kidney, and nervous system (Suhartono et al., 2015a;

Suhartono et al., 2016; Khorasgani et al., 2013).

Also, Cd could affect some metabolism pathway

including glucose metabolism (Suhartono et al.,

2015b).

It has been found that Cd could decreased the

glycogen reserves and increased the glucose levels

in liver homogenate (Suhartono et al., 2015b). Also,

Bashir et al. (2014) study have shown that Cd could

increased the level of plasma glucose and decreased

the level of liver glycogen. Several investigators

have confirmed that Cd could affect the glucose

metabolism via several pathway. Cd altered activites

of carbohydrate metabolizing enzymes, including

hexokinase, glucokinase, phosphofructokinase and

amylase (Navaneethan et al., 2014; Bajo et al., 2014;

Slencu et al., 2014). Also, Cd could induced the liver

and pancreas cells damaged resulted in glucose

metabolism alteration (Khorasgani et al., 2014;

Suhartono et al., 2015b).

It has been long appreciated that Cd toxicity

could prevent by a number of natural antioxidants.

156

Suhartono, E., Oktaviani, I., Adenan, . and Thalib, I.

The Protective Efﬁcacy of Kelakai (Stenochlaena Palustris) on Cadmium-induced Glucose Metabolism Alteration In Vitro.

DOI: 10.5220/0008788101560162

In Proceedings of the 2nd Syiah Kuala International Conference on Medicine and Health Sciences (SKIC-MHS 2018), pages 156-162

ISBN: 978-989-758-438-1

In particular, kelakai (S. palustris), a local plants that

growth in Indonesia, especially South Kalimantan

known to be rich source of antioxidants. Our

previous reports shows that S. palustris contains

flavonoid and possess several antioxidants activities

(Suhartono et al., 2012). Also, another previous

study suggest that the S. palustris extracts can slow

down the formation of MG, AOPPs, and PC in

bovine serum albumin in vitro (Suhartono et al.,

2016).

In view of the antioxidant properties of S.

palustris, it is noteworthy to consider that S.

palustris might bring out beneficial effects on Cd-

induced glucose metabolism alteration in vitro.

Therefore, the present study has been designed to

evaluate the protective efficacy of S. palustris on

Cd-induced glucose metabolism alteration in vitro.

2 MATERIAL AND METHODS

2.1 Collection and Extraction of Plant

Materials

The fresh leaves of S. palustris were obtained from

Gambut subdistrict, South Kalimantan, Indonesia in

February 2016 and identified by Department of

Biology, Pharmacy Study Program, Faculty of

Mathematics and Natural Sciences, Lambung

Mangkurat University, South Kalimantan, Indonesia.

The plant parts were separated, shade dried and

powdered. Then, Powdered material of S. palustris

leaves is taken for maceration with 150 ml of

distilled water for 1 hr on rotary shaker. The extract

then filtered using muslin cloth and Whatman no.1

filter paper and concentrated by evaporation on

water bath (Suhartono et al., 2012).

2.2 Experimental Section

The liver and pancreas samples were obtained from

32 old male rats (Rattus novergicus) with 2-3-

month-old, weighing 200-250 g. The liver and

pancreas samples were taken surgically with

ketamine as anaesthesia. Experiments performed

complied with the rulings of the Institute of

Laboratory Animal Resources, Commission on Life

Sciences, National Research Council and were

approved by the Ethical Committee of the Faculty of

Medicine, University of Lambung Mangkurat,

Banjarbaru, South Kalimantan, Indonesia.

The liver and pancreas samples then fixed in

phosphate buffer solutions at pH 7.0. The liver and

pancreas samples for analysis were homogenized,

respectively. The homogenates were centrifuged at

3500 rpm for 10 min and the top layer was taken and

stored until it uses.

Liver and pancreas samples were divided into 4

groups with 6 samples of in each group. Group 1

(T1): liver or pancreas homogenates + 0.3 mg/l

cadmium sulphate (CdSO

); group 2 (T2): liver or

pancreas homogenates + 0.3 mg/l CdSO

+ 5 mg/l of

aqueous extracts of S. palustris; group 3 (T3): liver

or pancreas homogenates + 0.3 mg/l CdSO

+ 10

mg/l of aqueous extracts of S. palustris; group 4

(T4): liver or pancreas homogenates + 0.3 mg/l

CdSO

+ 15 mg/l of aqueous extracts of S. palustris.

Each solution then incubated at 37°C for 1 hour.

After incubation, pancreas amylase activity, liver

glucokinase activity, liver glycogen, glucose, and

MG concentration was estimated.

2.3 Pancreas Amylase Activity Analysis

The pancreas amylase activity was measured

according to the Smith and Roe method (Smith and

Roe, 1949). Pipette 5 ml of 1.2% starch solution (60

mg) at approximately 90

C, 3 ml of phosphate

buffer, and 1 ml of 0.5 M sodium chloride into each

of two test-tubes. Into a third tube (C), the blank,

pipette 5 ml of distilled water, 3 ml of phosphate

buffer, and 1 ml of 0.5 M sodium chloride. Place all

tubes in a water bath at 37oC until they have reached

the temperature of the water bath. To Tube A, add 1

ml of enzyme solution. Keep all tubes in the water

bath for exactly 30 minutes. Promptly add 2 ml of

N-hydrochloric acid to each tube. This brings the pH

below 2, a step that stops amylase action in the

digest tube and prevents action of the enzyme next

added to the control tube. Add 1 ml of enzyme

solution to tubes B (control) and C (blank) and mix

thoroughly. Pipette 2 ml of each of these reaction

mixtures into appropriately labelled 500 ml

volumetric flasks containing about 400 ml of

distilled water and 5 ml of N-hydrochloric acid. Add

1 ml of iodine reagent to each flask and make up to

volume. The resulting blue solutions are decanted

into cuvettes and read in a photoelectric calorimeter

at a wave-length of 620 mp. Solution from Tube B

gives the iodine colour value without amylase action

and solution from Tube A gives the value after

enzyme action.

Calculations – Let D = 2 – log G = Optical Density

(D of Control) – (D of Digest) X 60 = mg of starch hydrolysed

(D of Control)

The Protective Efﬁcacy of Kelakai (Stenochlaena Palustris) on Cadmium-induced Glucose Metabolism Alteration In Vitro

157

The amylase unit is defined as the amount of

enzyme that under the conditions of this procedure,

with 60 mg. of starch present, will hydrolysed 10

mg. of starch in 30 minutes to a stage at which no

colour is given with iodine at 620 rnp. The definition

of this amylase unit was established to make the unit

conform as closely as possible to the units of

methods in general use.

2.4 Liver Glucokinase Activity

Analysis

Glucose concentration (100 mM, 200 mM, 300 mM,

400 mM and 500 mM), each concentration was

taken added 3 ml and 3 ml of phosphate buffer pH 7.

Furthermore, mixed until homogeneous. A total of 1

ml homogenate is added to each mixture, and then

measured as the levels of glucose [G0]. After 20

minutes, each mixture of glucose is measured again

[G1] by the method of hydrolytic Duboie's. The rate

of oxidation of glucose by glucokinase (v) is

expressed in changes in the concentration of glucose

per minute (Bustos and Iglesias, 2000).

2.5 Liver Glycogen Level Analysis

This assay was performed as described by Bidinotto

et al. (Bidinotto et al., 1997) Samples of liver were

quickly separated from freeze tissues and transferred

to essay tubes containing 1.0 ml of 6 mol/l

potassium hydroxide (KOH). The tubes were

transferred to a boiling water bath and left along 3-5

min for complete dissolution. Aliquots of the

resultant solution (250 μl) were added to 3 ml of

95% ethanol-water and after mixing, 100 μl of 10%

potassium sulphate (K

) was appended. A

cloudy white precipitate was formed and the

supernatant was discharged after centrifuging at

3000 rpm for 3 min. It was added 2.5 ml of distilled

water to the precipitate, which was promptly

dissolved. Suitable aliquots from such solution were

employed to Dubois reaction. Glycogen

concentration is expressed in μmol of glucosil-

glucose per g of wet tissue.

2.6 Liver Glucose Level Analysis

Liver tissues were homogenized in 50%

Trichloroacetic Acid (TCA), keeping the proportion

of 100 mg per 1.0 ml of TCA. After centrifuging for

5 min at 5000 rpm, the contents of glucose were

determined in the supernatant. Homogenate samples

were submitted to the same procedure, keeping the

same proportions (100 μl of homogenate/1.0 ml

TCA). Glucose was determined by Dubois

hydrolytic method. It consists of a suitable aliquot of

glucose into a final volume of 0.5 ml added of 0.7

ml of 3% phenol. After shaking, 2 ml of

concentrated sulfuric acid (H

) was added into

one stroke developing strong heat of reaction. The

product was determined at 540 nm in a single

colorimeter (Bidinotto et al., 1997).

2.7 Liver MG Level Analysis

MG compounds are measured using modified

Dinitro-Phenyl hydrazine (DNPH) method

(Suhartono et al., 2014). From each test solution, 0.5

ml solution was taken, and then each solution was

divided to 2 tubes with 0.25 ml volume in each tube.

The first tube was the sample (A) and the second

tube was blank (B) solution. Then 1 ml DNPH were

added into each A tube and 1 ml HCl 2.5 mol/l into

each B tube. The tubes were incubated for 45 min in

room temperature and protected from light, and then

tubes were shaken with a vortex for 15 min. The

next step is added 1 ml of TCA 20% into each tube

(A and B), then the tubes were incubated for 5 min.

Tubes were centrifuged for 5 min with 1400 rpm of

speed to separate the supernatant. The pellets are

centrifuged and washed three times with the addition

of 1 ml ethanol-ethyl acetate. The last step was

added 1 ml of urea 9 mol/l and incubates the

solution for 10 min in 37

C while it was shaken. The

solution was centrifuged again for 5 min in 1400

rpm of speed. Then the absorbance of tube A and B

were measured at λ = 390 nm (ΔA).

Furthermore, a total of 25 μl of the homogenate

was added to 350 μl DNPH (0.1% DNPH in 2 mol/l

HCl) and then 2.125 ml distilled water was added. It

is incubated for 15 min at 37°C, then 1.5 ml NaOH

10% was added. Absorbance was measured at λ =

576 nm (A1).

MG level was calculated following to equation:

MG Level (%) = A1 X 100%

ΔA

2.8 Statistical Analysis

The results were expressed as mean ± SE for six

replicates. Significance of mean differences of all

parameters between group of treatments were

SKIC-MHS 2018 - The 2nd Syiah Kuala International Conference on Medicine and Health Sciences

158

statistically compared using Kruskal-Wallis test and

followed by Mann-Whitney test for multiple range

test. Significance was set at P<0.05. The software

used for the data analysis were the Statistical

Package for the Social Sciences (SPSS) version 16.0

and Microsoft Excel 2010 for Windows Vista.

3 RESULTS

This present study which was undertaken to assess

the protective effects of S. palustris on Cd-induced

glucose metabolism alteration in in vitro condition.

Several parameters were measured such as, amylase

pancreas, liver glucose, glycogen, and MG level, and

liver glucokinase activity.

Figure 1 shows the mean comparison for

pancreas amylase activities between group of

treatments. The activity of pancreas amylase is

higher in T1 group than all group of treatments.

Treatment with S. palustris led to lower pancreas

amylase activity, with the lowest activity is in T4

group. Kruskal-Wallis test results shows that all

groups of treatment are significantly (p<0.05)

different. Then, we used Mann-Whitney test for

multiple comparison test. b, c, d, and e indicate that

significant differences compared with T1, T2, T3,

and T4 group, respectively. Mann-Whitney test

results show that there is a significant difference

between a group of treatments except between T1-

T2.

Figure 1: Comparison of pancreas amylase activity

between group of treatments. Values are mean ± SEM of

six replicates in each group treatments. b: Significantly

different when compared to Group T1; c: Significantly

different when compared to Group T2. d: Significantly

different when compared to Group T3; and e: Significantly

different when compared to Group T4. Comparison of

variables between the groups was performed with

Kruskal-Wallis test and followed by Mann-Whitney U test

(P<0,05).

Figure 2 shows the mean comparison for liver

glucokinase activities between group of treatments.

The activity of liver glucokinase were lower in T1

group compared with the all group of treatments.

Also, the result shows that the activity of liver

glucokinase seems higher, with the highest activity

is in group T4. Kruskal-Wallis test results shows that

all groups of treatment are significantly (p<0.05)

different. Also, b, c, d, and e indicate the significant

differences compared to T1, T2, T3, and T4 group,

respectively. Mann-Whitney test results show that

there is a significant difference between a group of

treatments except between T2-T3.

Figure 2: Comparison of liver glucokinase activity

between group of treatments. Values are mean ± SEM of

six replicates in each group treatments. b: Significantly

different when compared to Group T1; c: Significantly

different when compared to Group T2. d: Significantly

different when compared to Group T3; and e: Significantly

different when compared to Group T4. Comparison of

variables between the groups was performed with

Kruskal-Wallis test and followed by Mann-Whitney U test

(P<0,05).

Figure 3 represented the mean values ± standard

error (mean ± SEM) of liver glucose concentration.

Dispersion of measured values around each mean

varied from 23.661 to 42.883 mM. The data from

figure 3 shows that T1 group have a higher liver

glucose concentration than another group of

treatments, while T2-T4 group have a lower liver

glucose concentration than T1 group. Kruskal-

Wallis test results shows that all groups of treatment

are significantly (p<0.05) different. The letters

indicate the multiple comparison using Mann-

Whitney test as mentioned above. Mann-Whitney

test results show that there is a significant difference

between a group of treatments except between T1-

T2, and T2-T3.

Figure 4 represented the mean values ± standard

error (mean ± SEM) of liver glycogen concentration.

Dispersion of measured values around each mean

varied from 0.600 to 2.599 glucosil-glucose µmol/gr

The Protective Efﬁcacy of Kelakai (Stenochlaena Palustris) on Cadmium-induced Glucose Metabolism Alteration In Vitro

159

wet tissue. The data from figure 4 shows that T1

group have a lower liver glycogen concentration

than another group of treatments, while T2-T4 group

have a higher liver glycogen concentration than T1

group. Kruskal-Wallis test results shows that all

groups of treatment are significantly (p<0.05)

different. Also, the letters indicate Mann-Whitney

test results. Mann-Whitney test results show that

there is a significant difference between a group of

treatments except between T1-T2, and T3-T4.

Figure 3: Comparison of liver glucose level between group

of treatments. Values are mean ± SEM of six replicates in

each group treatments. b: Significantly different when

compared to Group T1; c: Significantly different when

compared to Group T2. d: Significantly different when

compared to Group T3; and e: Significantly different when

compared to Group T4. Comparison of variables between

the groups was performed with Kruskal-Wallis test and

followed by Mann-Whitney U test (P<0,05).

Figure 4: Comparison of liver glycogen level between

group of treatments. Values are mean ± SEM of six

replicates in each group treatments. b: Significantly

different when compared to Group T1; c: Significantly

different when compared to Group T2. d: Significantly

different when compared to Group T3; and e: Significantly

different when compared to Group T4. Comparison of

variables between the groups was performed with

Kruskal-Wallis test and followed by Mann-Whitney U test

(P<0,05).

Figure 5 shows the mean comparison for liver MG

level between group of treatments. The level of MG

was higher in T1 group than another group of

treatments. Also, the result shows that the level of

liver MG seems lower, with the lowest level are in

group T3 and T4. Kruskal-Wallis test results shows

that all groups of treatment are significantly

(p<0.05) different. The letters indicate Mann-

Whitney test results. Mann-Whitney test results

show that there is a significant difference between a

group of treatments except between T1-T2, and T3-

T4.

2.2.1

Title

Figure 5: Comparison of liver MG level between group of

treatments. Values are mean ± SEM of six replicates in

each group treatments. b: Significantly different when

compared to Group T1; c: Significantly different when

compared to Group T2. d: Significantly different when

compared to Group T3; and e: Significantly different when

compared to Group T4. Comparison of variables between

the groups was performed with Kruskal-Wallis test and

followed by Mann-Whitney U test (P<0,05).

4 DISCUSSION

It is widely known that the pancreas and liver play

an important role in glucose metabolism (Pap, 2004;

Kalsbeek et al., 2014). Pancreas secrete hormones

such as insulin and glucagon, and several enzymes

such as, amylase (Pap, 2004), while liver balancing

glucose entry into and out of the circulation

(Kalsbeek et al., 2014; Bechmann et al., 2012).

Thus, the effect of protective agents on tissues such

as the liver and pancreas that regulate glucose

metabolism is an interesting area to explore.

In this present study, we investigate the

protective effect of S. palustris on Cd-induced

glucose metabolism in vitro by measuring several

parameters such as pancreas amylase activity, liver

glucokinase activity, liver glucose, glycogen, and

MG level. From the result, in can be seen that Cd

exposure increase amylase activity. The results of

our studies are supported by the other research by

SKIC-MHS 2018 - The 2nd Syiah Kuala International Conference on Medicine and Health Sciences

160

Khorasgani et al. (2013). Results of that study

showed that Cd could increase the amylase activity

level in a pancreas of rats. Also, El-Aziz and El-

Mottaleb (2015) results showed the same effect but

in amylase activity in a serum of rats. The increasing

of amylase activity has known as a result from

pancreatitis or from damage amylase secretory cells

by Cd (Abedi et al., 2013). Result of this present

study also suggested that S. palustris extract shows a

protective effect especially in higher concentration.

This protective effect might be the presence of

phenolic compounds in S. palustris extracts. These

results are consistent with our previous report which

found that the S. palustris extracts comprise

flavonoid and possess some antioxidant activity

(Suhartono et al., 2012). This could inhibit the

pancreatitis and chelate some metal including Cd to

improve the amylase activity.

Results of this present study also indicated that

Cd exposure led to increase the glucose level and

decrease the glycogen level in a liver of rats. These

results are consistent with several previous reports

(Suhartono et al., 2015b; Bashir et al., 2014; Bhati et

al., 2014; Al Rikabi and Jawad, 2013; Sobha et al.,

2007). According to several previous reports, Cd

could induce the liver cells damage by interrupt the

pro- and anti-oxidant balance (Matovic et al., 2011;

Skipper et al., 2016; Suhartono et al., 2013). The

result of this present study indicated that S. palustris

extract could improve the level of glucose and

glycogen in liver cells homogenate, again better

protective effect in greater kelakai concentration.

This result was similar with our previous reports but

with bark and leave of Nothaphoebe coriacea extract

(Suhartono et al., 2016). The reason why S. palustris

have a protective effect to inhibited the Cd-induced

glucose metabolism alteration may be the same

reason as mentioned in the previous paragraph in

this section.

According to the result of this present study, Cd

exposure could affect the MG level in liver cells

homogenate. These results contrast with our

previous report. Our previous report show that Cd

could decrease the MG level in liver cells

homogenate (Suhartono et al., 2015). However, in

another several previous reports Cd could induced

the formation of MG both in in vitro and in vivo

condition, but in another organs, such as kidney

(Suhartono et al., 2016; Suhartono et al., 2014;

Husna et al., 2014). It is well known that MG is the

precursor of quantitatively important advanced

glycation end products (AGEs) (Rabbani and

Thornalley, 2014). MG is form via several

mechanism, including auto-oxidation of glucose,

which leads to glyoxal formation, decomposition of

amadori products (3-deoxyglucosone) and

fragmentation of glycerinaldehyde-3-phosphate and

dihydroxyacetone phosphate during glycolysis

(Jorgens et al., 2015).

5 CONCLUSIONS

S. palustris extracts possesses a protective effect

against Cd-induced glucose metabolism alteration in

vitro. The protective effects might be some

phytochemical constituents contained in S. palustris

extracts. Further studies will be worthwhile to

explore the exact phytochemicals constituents in S.

palustris extract and molecular protective effect

mechanism S. palustris extract.

REFERENCES

Abedi Z, Hasantabar F, Khalesi MK, Babaei S. 2013.

Effect of sublethal concentrations of cadmium, lead

and chromium on some enzymatic activities of

common carp; Cyprinus carpio. World Journal of

Zoology, 8 (1), pp. 98-105.

Al Rikabi AA and Jawad AADH. 2013. Protective effect

of ethanolic ginger extract against cadmium toxicity in

male rabbits. Basrah Journal of Veterinary Research,

12, pp. 13-29.

Anyakora C, Ehianeta T, Umukoro O. 2013. Heavy metal

levels in soil samples from highly industrialized Lagos

environment. African Journal of Environmental

Science and Technology, 7 (9), pp. 917-924.

Bajo MJR, Atauri P, Ortega F, Westerhoff HV, Gelpi JL,

Centelles JJ, Cascante M. 2014. Effects of cadmium

and mercury on the upper part of skeletal muscle

glycolysis in mice. PLoS One, 9(1), e80018. DOI:

10.1371/journal.pone.0080018.

Bashir N, Manoharan V, Prabu SM. 2014. Ameliorative

effects of grape seed proanthocyanins on cadmium

induced metabolic alterations in rats. International

Journal of Biological Research, 2, pp. 28-34.

Bechmann LP, Hannivoort RA, Gerken G, Hotamisligil

GS, Trauner M, Canbay, A. 2012. The interaction of

hepatic lipid and glucose metabolism in liver diseases.

Journal of Hepatology, 56, pp. 952–964.

Bhati Sl, Ranga D, Meena DC, Agarwal M, Chakrawarti

A, Purohit RK. 2014. Ameliorative effect of Emblica

officinalis in mice liver. World Journal of

Pharmaceutical Research, 3, pp. 846-863.

Bidinotto PM, Moraes G, Souza RHS. 1997. Hepatic

glycogen and glucose in eight tropical fresh water

teleost fish: a procedure for field determinations of

micro samples. B Tec Cepta Pirassununga, 10, pp. 53-

60.

The Protective Efﬁcacy of Kelakai (Stenochlaena Palustris) on Cadmium-induced Glucose Metabolism Alteration In Vitro

161

Bustos DM and Iglesias AA. 2000. The kinetic properties

of liver glucokinase and its function in glucose

physiology as a model for the comprehensive study of

enzymes' kinetic parameters and reversible inhibitors.

Biochemistry and Molecular Biology, 28 (6), pp. 332-

337.

El-Aziz EA and El-Mottaleb NAA. 2015. The potential

protective effects of tetrahydrobiopterin on cadmium-

induced pancreatic changes in male rats. Bulletin

Egypt Social Physiological Science, 35 (3), pp. 62-74.

Husna AH, Ramadhani EA, Eva DT, Yulita AF,

Suhartono E. 2014. The role formation of

methylglyoxal, carbonyl compound, hydrogen

peroxide and advance oxidation protein product

induced cadmium in ovarian rat. International Journal

of Chemical Engineering and Application, 5 (4), pp.

319-323.

Jorgens, K, Stoll SJ, Pohl J, Fleming TH, Sticht C,

Nawroth PP, Hammes HP, Kroll J. 2015. High tissue

glucose alters intersomitic blood vessels in zebrafish

via methylglyoxal targeting the VEGF receptor

signalling cascade. Diabetes, 64, pp. 213-225.

Kalsbeek, Andries, Fleur S, Fliers E. 2014. Circadian

control of glucose metabolism. Molecular Metabolism,

3(4), pp. 372–383.

Khorasgani EM, Haghdoost IS, Sedaghat R, Mortazavi P,

Roghani M. 2013. Satureja hortensis L. alcoholic

extract ameliorates cadmium-induced pancreatic

damage in rats. Middle-East Journal of Science

Research, 15 (1), pp. 32-35.

Matovic V, Buha A, Bulat Z, Dukic-Cosic D. 2011.

Cadmium toxicity revisited: focus on oxidative stress

induction and interactions with zinc and magnesium.

Arhiv Hig Rada Toksikol, 62(1), pp. 65-75.

Navaneethan D and Rasool MK. 2014. An experimental

study to investigate the impact of p-coumaric acid, a

common dietary polyphenol, on cadmium chloride-

induced renal toxicity. Food Function, DOI:

10.1039/c4fo00346b.

Pap A. 2004. Effects of insulin and glucose metabolism on

pancreatic exocrine function. International Journal of

Diabetic Metabolism, 12, pp. 30-34.

Rabbani N and Thornalley PJ. 2014. The critical role of

methylglyoxal and glyoxalase 1 in diabetic

nephropathy. Diabetes, 63, pp. 50-52.

Rahman M, Gul S, Ajmal M, Iqbal A, Achakzai A. 2014.

Removal of cadmium from aqueous solutions using

excised leaves of quetta pine (Pinus halepensis mill.).

Bangladesh Journal of Botany, 43 (3), pp. 277-281.

Skipper A, Sims JN, Yedjou CG, Tchounwou PB. 2016.

Cadmium chloride induces DNA damage and

apoptosis of human liver carcinoma cells via oxidative

stress. International Journal of Environmental

Research and Public Health, 13 (88), pp. 1-10.

Slencu BG, Ciobancu C, Solcan C, Anton A, Ciobanu St,

Solcan Gh, Cuciureanu R. 2014. Effect of selenium

supplementation on serum amylase, lactate

dehydrogenase and alkaline phosphatase activities in

rats exposed to cadmium or lead. Agronomical

Research in Moldavia, XLVII (4), pp. 160.

Smith BW and Roe JH. 1949. Photometric method for the

determination of α-amylase in blood and urine, with

use of starch-iodine colour. Journal of Biological

Chemistry, 179, pp. 53-59.

Sobha K, Poornima A, Harini P, Veeraiah K. 2007. A

study on biochemical changes in the fresh water Fish,

Catla catla (Hamilton) exposed to the heavy metal

toxicant cadmium chloride. Kathmandu University

Journal of Sciences Engineering and Technology, I,

pp. 1-11.

Suhartono E, Viani E, Rahmadhan MA, Gultom IS,

Rakhman MF, Indrawardhana D. 2012. Screening of

medicinal plant for total flavonoid and antioxidant

activity in South Kalimantan of Indonesian.

International Journal of Chemical Engineering and

Applications, 3 (4), pp. 297-299.

Suhartono E, Triawanti, Yunanto A, Firdaus RT, Iskandar.

2013. Chronic cadmium hepatooxidative in rats:

treatment with haruan fish (Channa striata) extract.

APCBEE Procedia, 5, pp. 441-445.

Suhartono E, Triawanti, Leksono AS, Djati MS. 2014. The

role of cadmium in protein glycation by glucose:

Formation of methylglyoxal and hydrogen peroxide in

vitro. Journal of Medical and Biological Engineering,

3, pp. 59-62.

Suhartono E, Iskandar, Hamidah S, Arifin YF. 2015a.

Phytochemical constituents’ analysis and

neuroprotective effect of leaves of gemor

(Nothaphoebe Coriacea) on cadmium-induced

neurotoxicity in rats: An in-vitro study. International

Journal of Toxicological and Pharmacological

Research, 7(6), pp. 297-302.

Suhartono E, Santosa PB, Iskandar. 2015b. Ameliorative

effects of different parts of gemor (Nothaphoebe

coriacea) on cadmium induced glucose metabolism

alteration in vitro. International Journal of

Pharmaceutical and Pharmacological Science, 7 (11),

pp. 1-4.

Suhartono E, Bahriansyah M, Triawanti. 2016. The

inhibition effect of kelakai (Stenochlaena palustris)

extract on cadmium-induced glycation and fructation

in-vitro. International Journal of Pharmaceutical and

Clinical Research, 8 (4), pp. 248-253.

SKIC-MHS 2018 - The 2nd Syiah Kuala International Conference on Medicine and Health Sciences

162