LEVEL OF LIPID PROFILE AND LIVER

ENZYME OF DIABETIC MALE RATS

INDUCED BY STREPTOZOTOCIN TREATED

WITH FORXIGA

Wala'a. H. Hadi

College of Nursing, National University of Science & Technology, Iraq

wala.h.hadi@nust.edu.iq - https://orcid.org/0000-0001-9940-4539

Teeba T. Khudair

College of Nursing, National University of Science & Technology, Iraq

taiba.th.khudair@nust.edu.iq - https://orcid.org/0000-0001-8701-797X

Prof. Dr. Khalid G. Al-Fartosi

College of Nursing, National University of Science & Technology, Iraq

khalidalartosi@yahoo.com

Reception: 31/10/2022 Acceptance: 05/01/2023 Publication: 23/01/2023

Suggested citation:

H. H., Wall’s, T. K., Tea and G. A., Khalid (2023). Level of lipid proﬁle and liver

enzyme of diabetic male rats induced by streptozotocin treated with

forxiga. 3C Empresa. Investigación y pensamiento crítico, 12(1), 273-288.

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ABSTRACT

The present study including study Level of lipid profile and liver enzyme of diabetic

male rats induced by streptozotocin The study was carried out in the animal house of

the Biology Department, College of Science, University of Thi-Qar ,Iraq. Thirty lab

male rats were used in this study, and divided into five groups (6 rats for each group).

Thirty male rats (190-210 gm) were randomly divided into five groups and placed in

cages according to the groups, containing 6 rats per group as following. Group1,

considered as the negative control group, given food and water for a period of 30

days. Group 2, served as the diabetic positive control, given streptozotocin were

injected I.P. 60 mg/kg b.w. as a single dose with food and water for 15 days. Group 3,

received streptozotocin were injected I.P (60 mg/kg) with food and water for 15 days,

then treated with forxiga 1mg/kg administrated orally every day for a period of 15

days. Group 4, given were injected I.P streptozotocin (60 mg/kg) with s food and

Water for 30 days. Group 5, received streptozotocin were injected I.P (60 mg/kg) with

food and water. Then treated with forxiga1mg/kg administrated orally every day for a

period of 15 day. At the end of experimental, all rats were euthanized, blood sample

were obtained for bio chemical parameters.

KEYWORDS

Lipid profile, liver enzyme ,Streptozotocin, Diabetic rats, forxiga

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PAPER INDEX

ABSTRACT

KEYWORDS

1. INTRODUCTION

2. MATERIAL AND METHODS

2.1. INDUCTION OF DIABETES MELLITUS

2.2. EXPERIMENTAL DESIGN

2.3. BLOOD SAMPLES

2.4. MEASUREMENT OF GLUCOSE LEVEL (MG/DL)

2.5. MEASUREMENT OF LIPID PROFILE

2.5.1. TOTAL CHOLESTEROL LEVEL (TC) (MG/DL)

2.5.2. TRIGLYCERIDES LEVEL(TG) (MG/ML)

2.5.3. HIGH DENSITY LIPOPROTEIN LEVEL (HDL) (MG/ML)

2.5.4. LOW DENSITY LIPOPROTEIN LEVEL (LDL) (MG/DL)

2.5.5. VERY LOW DENSITY LIPOPROTEIN (MG/ML)

2.6. MEASUREMENT OF LIVER ENZYME

2.6.1. ALANINE AMINOTRANSFERASES LEVEL (ALT)(U/L)

2.6.2. ASPARTATE AMINOTRANSFERASES LEVEL(AST) (U/L)

2.6.3. ALKALINE PHOSPHATASE LEVEL(ALP) (U/L)

3. RESULTS

3.1. EFFECT OF FORXIGA ON GLUCOSE LEVEL OF DIABETIC

MALE RATS

3.2. EFFECT OF FORXIGA ON LIPID PROFILE LEVEL OF

DIABETIC MALE RATS

3.3. EFFECT OF FORXIGA DRUG ON LEVEL OF LIVER ENZYME

OF DIABETES MALE RATS

4. CONCLUSION AND DISCUSSION

REFERENCES

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1. INTRODUCTION

Diabetes mellitus (DM), a disarray of carbohydrate metabolism, is a medical and

endocrinological set of symptoms characterized by hyperglycemia, high glycated

hemoglobin, and a high risk of morbidity and humanity (1). It is caused by absence or

diminish efficiency of endogenous insulin or the inappropriate use of insulin by goal

cells, and is characterized by unbalanced metabolism, hypertension, and squeal

principally distressing the vasculature (2). Experimental models in animals are used to

study a variety of aspects associated to the disease, such as its symptom,

development, and complication. They have also been second-hand in

pharmacological tests in the exploration for more successful drugs and treatments.

The diabetes model most often use absorb the supervision of a single high dose of

streptozotocin(STZ) or alloxan (ALX) to fully developed animals, which lead to the

damage of pancreatic β cells and reason hyperglycemia as a express consequence of

undersupplied insulin production (3). Forxiga exerts its glucose-lower property

through awkwardness of the SGLT2 protein in the kidney proximal tubule, resultant in

the excretion of glucose and calories into the urine(4). This lackluster energy balance

consequences in dapagliflozin treatment-associated weight loss, as has been

confirmed in a number of clinical Studies(5,6). Diabetic patients recurrently display a

progressive decline in muscle mass and impair muscle serviceable quality(7), which

are caused by concentrated insulin sensitivity and decreased mitochondrial role

payable underline pathogenesis of T2DM(8).Regarding SGLT2i induced weight

reduction, clinical concern has been raise over the event of sarcopenia(decrease in

muscle mass)(9 ,10) and clinical studies are therefore needed to establish the weight

loss efficacy and any belongings on muscle mass of dapagliflozin treatment in T2DM

patients(11).

Aim of this study to elevated Level of lipid profile and liver enzyme of diabetic male

rats induced by streptozotocin Treated with Forxiga.

2. MATERIAL AND METHODS

2.1. INDUCTION OF DIABETES MELLITUS

The male rats intraperitoneally injected by a single dose STZ (Sigma, Chemical ), 60

mg/kg body wt, dissolved in sodium citrate buffer (0.1 mol/liter, pH 4.5) at a

concentration of 20 mg/ml immediately before use. In order to prevent the onset of

severe hypoglycemia they have received a solution of 10% glucose instead of normal

drinking water over the 24 hours following the treatment. Streptozotocin induces

diabetes within 3 days by destroying the beta cells and a mean blood glucose > 250

mg/dL. Diabetic animals and non-diabetic control group were kept in metabolic cages

individually and separately and under feeding and metabolism control. Glucose in the

blood of diabetic rats exceeded that of the non-diabetic control ones. Diabetes rats

were treatment were with Forxiga drug (1mg /1kg/day) orally for 15 day. Animals used

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as normal control received standard rat pellet with ad libitum, distilled water till the end

of the experiment.

2.2. EXPERIMENTAL DESIGN

Thirty male rats (190-210 gm) were randomly divided into five groups and placed in

cages according to the groups, containing 6 rats per group as following.

1-Group1 :( Control group) considered as the negative control group, given food and

water for a period of 30 days.

2-Group 2: (DM group for 15 day) served as the diabetic positive control, given

streptozotocin were injected I.P.60 mg/kg b.w. as a single dose with food and water for

15 days.(12).

3-Group 3: (DM+ forxiga group for 15 ) received streptozotocin were injected I.P(60

mg/kg) with food and water for 15 days, then treated with forxiga 1mg/kg

administrated orally every day for a period of 15 days. (13).

4-Group4:(DM group for 30 day) given were injected I.P streptozotocin(60 mg/kg) with

s food and Water for 30 days

5- Group 5: (DM+ forxiga group for 30 ) received streptozotocin were injected I.P (60

mg/kg) with food and water. Then treated with forxiga1mg/kg administrated orally

every day for a period of 30 day.

At end of experiment measured body weight of animals and then sacrificed.

2.3. BLOOD SAMPLES

Blood were drawn from each animal in the experimental groups, by heart puncture

method after 12 hours fast and sacrificed by inhalation milddiethyl ether. Blood

samples were obtained by means of heart puncture. Using 5cc sterile syringes, the

sample was transferred into clean tube, left at room temperature for 15 minutes for

clotting, centrifuged at 3000 rpm for 15 minutes, and then serum was separated and

kept in a clean tube in the refrigerator at (-20ₒC) until the time of assay.

2.4. MEASUREMENT OF GLUCOSE LEVEL (MG/DL)

Test principle

Enzymatic situation method through hexokinase.4,5 Hexokinase (HK) catalyzes the

Phosphorylation of glucose through ATP to formglucose-6-

phosphate and ADP. To

follow the response, a second enzyme, glucose-6-

phosphate dehydrogenase

(G6PDH) is use to catalyze oxidation of glucose-6-

phosphate by NADP+ to form

NADPH (Titetz, 2006).

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D-glucose + ATP D-glucose-6-phosphate + ADP

D-glucose-6-phosphate + NADP+ D-6-phosphogluconate + NADPH + H+

GPDH

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The attentiveness of the NADPH formed is directly proportional to the glucose

concentration. It is determined by measuring the raise in absorbance at 340 nm.

Reagents - working solutions

2.5. MEASUREMENT OF LIPID PROFILE

2.5.1. TOTAL CHOLESTEROL LEVEL (TC) (MG/DL)

Enzymatic, colorimetric technique Cholesterol esters are cleave by the action of

cholesterol esterase to yield free cholesterol and fatty acids. Cholesterol oxidize then

catalyzes the oxidation of cholesterol to cholest-4-en-3-one and hydrogen peroxide. In

the attendance of peroxides, the hydrogen peroxide formed effects the oxidative

coupling of phenol and 4-aminoantipyrine to form a red quinone-imine dye.

The color concentration of the dye formed is directly proportional to the cholesterol

concentration. It is determined by measuring the increase in absorbance at 512 nm.

Reagents - working solutions

MES buﬀer: 5.0 mmol/L; pH 6.0; Mg2+: 24 mmol/L;

ATP: ≥ 4.5 mmol/L; NADP+: ≥ 7.0 mmol/L

HEPES buﬀer: 200 mmol/L; pH 8.0; Mg2+: 4 mmol/L; HK (yeast):≥ 300 μkat/L;

G6PDH (microbial): ≥ 300 μkat/L

Cholesterol esters + H2O cholesterol + RCOOH

Cholesterol + O2 cholest-4-en-3-one + H2O2

2 H2O2 + 4-AAP + phenol quinone-imine dye + 4 H2O

CE →

CHOD →

POD →

PIPESa) buﬀer: 225 mmol/L, pH 6.8; Mg2+: 10mmol/sodium

cholate: 0.6 mmol/L; 4-aminoan[pyrine: ≥ 0.45 mmol/L;

phenol: ≥ 12.6 mmol/L; fa]y alcohol polyglycol ether: 3 %;

cholesterol esterase (Pseudomonas spec.): ≥ 25 μkat/L

(≥ 1.5 U/mL); cholesterol oxidase (E. coli): ≥ 7.5 μkat/L

(≥ 0.45 U/mL); peroxidase (horseradish): ≥ 12.5 μkat/L

(≥ 0.75 U/mL); stabilizers; preserva[vea) PIPES = Piperazine-1,4-bis(2-

ethanesulfonic acid.

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Pipetting parameters

Diluent (H2O)

R 47 µL70 µL

Sample 2 µL23 µL

Total volume 142 µL

Calculation

Result =

2.5.2. TRIGLYCERIDES LEVEL(TG) (MG/ML)

Test principle

Enzymatic colorimetric test (sidelet al .,1993).

Reagents - working solutions

R is in position B

Pipetting parameters

Diluent (H2O)

R 120 µL

Sample 2 µL28 µL

Total volume 150 µL

Abs(A ssa y)

Abs(s ta n d ar d)

x St a n d ar dcon ce nt r at ion

(m m ol

)

triglycerides + 3 H2O glycerol + 3 RCOOH

glycerol + ATP glycerol-3-phosphate + ADP

glycerol-3-phosphate + O2 dihydroxyacetone phosphate + H2O2

H2O2 + 4-aminophenazone + 4-chlorophenol

4-(p-benzoquinone-monoimino)-phenazone + 2 H2O + HCl

L PL →

GK →

GPO →

Per ox i d a se →

PIPES buﬀer: 50 mmol/L, pH 6.8; Mg2+: 40 mmol/L;sodium

cholate: 0.20 mmol/L; ATP: ≥ 1.4 mmol/L; 4-aminophenazone:

≥ 0.13 mmol/L; 4-chlorophenol: 4.7 mmol/L; LPL (microbial):

≥ 83 μkat/L; GK (microbial): ≥ 3 μkat/L; GPO (microbial):

≥ 41 μkat/L; POD (horseradish): ≥ 1.6 μkat/L; preserva[ve;

stabilizers

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Calculation

Result =

2.5.3. HIGH DENSITY LIPOPROTEIN LEVEL (HDL) (MG/ML)

Test principle

Homogeneous enzymatic colorimetric assay. In the attendance of magnesium ions

and dextran sulfate, water-soluble complexes with LDL, VLDL, and chylomicrons are

form which are resistant to PEG-modified enzymes. The cholesterol special

management of HDL cholesterols single-minded enzymatically by cholesterol

esterase and cholesterol oxides couple with PEG to the amino groups

(approximately40 %). Cholesterol esters are busted down quantitatively into gratis

cholesterol and fatty acids by cholesterol esterase. In the presence of oxygen,

cholesterol is oxidized by cholesterol oxides to Δ4cholestenoneand hydrogen peroxi.

a) Sodium N-(2-hydroxy-3-sulfopropyl)-3,5-dimethoxyaniline.The color intensity of the

blue quinoneimine dye formed is directly proportional to the HDL-cholesterol

concentration. It is determined by measuring the increase in absorbance at 583 nm.

Reagents - working solutions

R1 is in position B and SR is in position C.

Pipetting parameters

Diluent (H2O)

R1 150 µL

Abs(A ssa y)

Abs(s ta n d ar d)

x St a n d ar dcon ce nt r at ion(200)mg /d

HDL-cholesterol esters + H2O HDL-cholesterol+ RCOOH

HDL-cholesterol + O2 Δ4-cholestenone + H2O2

2 H2O2 + 4-aminoan[pyrine + HSDA a) + H+ + H2O purple blue pigment + 5

H2O

PEG −ch ol es teoles ter a se →

PEG −ch ol es teolo xi d a se →

per ox id a se →

HEPES buﬀer: 10.07 mmol/L; CHES: 96.95 mmol/L, pH 7, sulfate: 1.5 g/L; magnesium

nitrate hexahyd rat> 11.7 mmol/L; HSDA: 0.96 mmol/L; as corbate oxides (Eupenicillium

sp., recombinant): > 50 μ/L; per oxides (horseradish): > 16.7 μt/L; preserva[ve

HEPES buﬀer: 10.07 mmol/L, pH 7.0; PEG cholesterol esterase(Pseudomonas

spec.): > 3.33 μ /L; PEG cholesterol oxides

(Streptomycin sp., recombinant): > 127 μ/L; per oxidize(horseradish): > 333 μ/L;

4-amino-an[pyrine: 2.46 mmol/L; preserva[ve

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Sample 2.5 µL7.0 µL

SR 50 µL

Total volume 209.5 µL

Calculation

Result =

2.5.4. LOW DENSITY LIPOPROTEIN LEVEL (LDL) (MG/DL)

Serum LDL concentration can be calculated by the following equation (Ram,1996).

L D L = Cholesterol con. – (HDL +TG/5) =

2.5.5. VERY LOW DENSITY LIPOPROTEIN (MG/ML)

By the following function:

VLDL= (TG\5)

2.6. MEASUREMENT OF LIVER ENZYME

2.6.1. ALANINE AMINOTRANSFERASES LEVEL (ALT)(U/L)

Test principle

Method according to the International Federation of Clinical Chemistry (IFCC), but

without pyridoxal-5'-phosphate.3,4ALT catalyzes the reaction between L-alanine and

2-oxoglutarate(Schumann et al .,2002). The pyruvate formed is reduced by NADH in a

reaction catalyzed by lactatedehydrogenase (LDH) to form Lactate and NAD+

Lalanine + 2-oxoglutarate pyruvate + Glutamate

pyruvate + NADH + H+ Lactate + NAD+

The rate of the NADH oxidation is directly proportional to the catalytic ALT activity. It is

determined by measuring the decrease in absorbance at340 nm.

Reagents - working solutions

R1 is in position B and SR is in position C.

Abs(sa m ple)

Abs(St a n d er)

×50 ×

(mmol /L)

ALT →

LDH →

TRIS buﬀer: 224 mmol/L, pH 7.3 (37 °C); Lalanine: 1120mmol/L; albumin (bovine): 0.25 %;

LDH (microorganisms): 45μkat/L; stabilizers; preserva[ve

2Oxoglutarate: 94 mmol/L; NADH: ≥ 1.7 mmol/L;preservate

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Pipetting parameters

Diluent (H2O)

R1 59 µL10 µL

Sample 11 µL26 µL

SR 17 µL9 µL

Total volume 132µL

2.6.2. ASPARTATE AMINOTRANSFERASES LEVEL(AST) (U/L)

Test principle

Method according to the International Federation of Clinical Chemistry(IFCC), but

without pyridoxal-5'-phosphate.3,4AST in the sample catalyzes the transfer of an

amino group between Aspartame and 2-

oxoglutarate to form oxaloacetate and

Glutamate. The oxaloacetate then reacts with NADH, in the presence of malatedehy

drogenase (MDH), to form NAD+

The rate of the NADH oxidation is directly proportional to the catalytic AST activity. It is

determined by measuring the decrease in absorbance at 340 nm.

Reagents - working solutions

R1 is in position A and SR is in position B and C.

Pipetting parameters

Diluent (H2O)

R140 µL29 µL

Sample 11 µL26 µL

SR 17 µL9 µL

Total volume 132µL

Aspartate + 2oxoglutarate oxaloacetate + Glutamate

Oxaloacetate + NADH + H+ malate + NAD+

AST →

MDH →

TRIS buﬀer: 264 mmol/L, pH 7.8 (37 °C); L-aspartate: 792

mmol/L;MDH (microorganism): ≥ 24 μ/L; LDH (microorganisms):≥ 48 μkat/L; albumin

(bovine): 0.preserva[ve

NADH: ≥ 1 .7 mmol/L; 2-oxoglutarate: 94 mmol/L; preserva[ve

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2.6.3. ALKALINE PHOSPHATASE LEVEL(ALP) (U/L)

Test principle

Colorimetric assay in accordance with a standardized method. In the presence of

magnesium and zinc ions, pnitrophenyl phosphate is cleaved by phosphatase into

phosphate and pnitrophenyl.

pnitrophenyl phosphate + H2O phosphate + pnitrophenyl

The pnitrophenyl released is directly proportional to the catalytic ALP activity. It is

determined by measuring the increase in absorbance at409 nm.

Reagents - working solutions

R1 is in position B and SR is in position C.

Pipetting parameters

Diluent(H2O)

R1 75 µL16 µL

Sample 2.75 µL20 µL

SR 17 µL10 µL

Total volume 140.75 µL

× n N=141,8 u/l

3. RESULTS

3.1. EFFECT OF FORXIGA ON GLUCOSE LEVEL OF DIABETIC

MALE RATS

The results as presented in table 1 indicated a significant increase (P≤

0.05) of

glucose concentration in DM and DM +forxiga groups (2,3,4and5)compared with

control group, while no significant different were recorded in STZ treated group for 15

days compare with group that treated for 30 days . However a significant (P≤

0.05)

increase in glucose level of group DM and DM +forxgia groups for 15 days. In

addition, significant (P≤ 0.05) increase in glucose level of group DM and DM +forxgia

groups for 30 days.

ALP →

2-amino-2-methyl-1-propanol: 1.724 mol/L, pH 10.44 (30 °C)magnesium

acetate: 3.83 mmol/L; zinc sulfate: 0.766 mmol/L;

N-(2-hydroxyethyl)-ethylenediaminetriace[c acid: 3.83 mmol/L

p-nitrophenyl phosphate: 132.8 mmol/L, pH 8.5 (25 °C);

preserva[ves

A L P =

Abssa m ple −Absbl a n k

Abss ta n d ar d

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Table 1. Effect of forxiga on glucose level of diabetic male rats.

*Values expressed as Mean ± SD(n=6)

*Different small letters denote significant deference (P ≤ 0.05) between experimental

groups.

3.2. EFFECT OF FORXIGA ON LIPID PROFILE LEVEL OF

DIABETIC MALE RATS

The results of lipids profile that found in the present study showed a significant

(P≤

0.05) increase in serum concentrations of CHOL and TG level in

groups(2,3,4and5) compared with control group. There was significant decrease in

serum concentrations CHOL and TG in DM group compared with DM (group 2) +

forxiga group for 15 days (group 3). The serum concentrations of CHOL and TG was

significant decrease in STZ administration group(group 4)compared with DM+forxiga

group(5).

In the table 2 the results indicated no significant changes in the serum concentration

of HDL in group(2,3 and 5) compared with control group. There was no significant

change in level of HDL in group(2)compared with group(3). While there was

significant(P≤0.05) increase of HDL level in group(5) compared with group(4).

In same table 2 the results indicated a significant increase (P≤

0.05) in the serum

concentration of groups(2,3,4 and 5) compared with control group. The serum

concentration LDL was no significant change in group(2) compared with group(3). But

there was no significant change in group (4) compared with group (5).

Glucose

(mg/dl)

Parameters

Groups

88.16 ± 8.75c

Group 1

Control group

329.33 ± 62.25a

Group 2

DM group (15 days )

150.50 ± 14.23b

Group 3

DM +Forxiga (15 days)

427.33 ± 230.02a

Group 4

DM group (30 days)

277.0 ± 42.70b

Group 5

DM +Forxiga (30 days)

146.57

L.S.D

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Lastly a significant increase (P≤

0.05)of the serum concentration of VLDL in DM and

DM+ forxiga groups(2, 3, 4, 5) compared with control group (1). The serum

concentration of VLDL a significant decrease in DM group compared with DM +

forxiga group for 15 days .A significant decrease (P≤

0.05)of the serum concentration

of VLDL in group administration of STZ (group 4) than those of administration of STZ

and treated with forxiga for 30 days(group 5) .

Table 2. Effect of forxiga on lipid profile level of diabetic male rats

*Values expressed as Mean ± SD (n=6)

*Different small letters denote significant deference (P ≤ 0.05) between experimental

groups.

3.3. EFFECT OF FORXIGA DRUG ON LEVEL OF LIVER ENZYME

OF DIABETES MALE RATS

The results represented in Table 3 revealed a significant increase (P≤

0.05) in serum

concentration of ALT, AST groups (2, 3, 4 and 5)compared with control group. A

significant decrease (P≤

0.05)in DM group(2) compared with DM +forxiga treated

group for 15 days (group 3).

On the other hand, ALT and AST concentrations in were significant

decrease(P≤0.05)in group(4) compared with group(5).

In same table 3, A significant increase (P≤0.05) in ALP concentration was recorded in

serum of the groups (2, 3, 4 and 5) compared with control group. There was no

significant change in group DM(group 2) compared with DM + forxiga treated group

Parameters

Group

Cholesterol

(mg/dl)

TGs

(mg/dl)

HDL

(mg/dl)

LDL

(mg/dl)

VLDL

(mg/dl)

Group 1

Control group

88.0 ±

5.54a60.0 ± 8.80d

33.33 ±

6.80ab

41.55 ±

4.42c11.66 ± 1.52d

Group 2

DM group (15 days )

128.83 ±

4.70b

165.50 ±

6.09b31.50 ± 5.0ab

64.23 ±

7.49ab 33.10 ± 1.21b

Group 3

DM +Forxiga (15 days)

122.50

±4.59c

140.0 ±

8.46c35.0 ± 6.44a

60.50 ±

9.88b28.0 ± 1.69 c

Group 4

DM group (30 days )

138.83 ±

3.48a

185.50 ±

8.50a

29.66 ±

5.60b

72.05 ±

6.50a37.11 ± 1.70a

Group 5

DM +Forxiga (30 days)

133.66 ±

6.28b

167.16 ±

5.94b36.0 ± 7.0a

63.40 ±

13.98ab 33.43 ± 1.18b

L.S.D 4.94 7.56 6.24 8.94 1.46

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for 15 days(group 3) and no significant change in DM (group 4) compared with DM +

forxiga treated group (group 5) for 30 days.

Table 3. Effect of forxiga drug on level of liver enzymes of diabetes male rats.

*Values expressed as Mean ± SD (n=6)

*Different small letters denote significant deference(P ≤ 0.05) between experimental

groups.

4. CONCLUSION AND DISCUSSION

Data in the present study showed administration of STZ alone cause significant

increase in the glucose as compared to the control group while When use forxiga,

glucose return to normal or close to normal compared with control groups.

Uncontrolled blood glucose levels cause conditions of high(hyperglycaemia) or low

(hypoglycaemia) blood sugar (14). Diabetes symptoms identify by raised blood

glucose, change lipids, carbohydrate, and enhance opportunity for diabetic difficulties

and oxidative stress (15,16). Low dosage streptozotocin is known to induce rapid

obliteration of pancreatic β

-cells lead to impaired glucose-stimulated insulin make

public and insulin resistance, both of which are marked features of type 2 diabetes.

The result showed significant increase in serum concentration of CHOL, TG, VLDL

and LDL in diabetic groups compared with control group, while there was a significant

decrease in level of HDL. Forxiga drug lead to significant improvement of serum

ALP(U/L)AST(U/L)

ALT(U/L)

Parameters

Groups

47.0±4.56c

31.83±2.13e

46.83±6.24d

Group 1

Control group

70.33±4.41b

62.16±7.62c

123.33±5.53b

Group 2

DM group (15 days )

67.48±0.87b

52.16 ±6.96d

102.83±13.10c

Group 3

DM +Forxiga (15 days)

92.16±9.90a

89.66±10.57a

139.83±6.21a

Group 4

DM group (30 days )

88.80±1.14a

74.0 ±12.31b

126.16 ±4.79b

Group 5

DM +Forxiga (30 days)

5.228.537.67

L.S.D

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concentration of CHOL, TG, VLDL and LDL , but there was significant increase in

level of HDL compared with diabetic groups.

Lipid and lipoprotein abnormality are frequent in the diabetic inhabitants due to the

effects of insulin shortage and insulin resistance on key metabolic enzymes (17).

Glucose tolerance, insulin resistance and plasma an insulin levels have been

implicate in abnormal plasma lipoprotein levels and hyperinsulinemia has been

associated with the development of atherosclerotic vascular complications in diabetic

patients . The result showed a significant increase in levels of (AST ,ALT and ALP) in

diabetic groups compared with control group but DM group which treated with forxiga

drug caused a significant improvement and return of serum AST and ALT to normal,

while no significant changes in serum ALP concentration compared with diabetic

group.

The analysis of the activities of these enzymes in the serum was used to observe the

condition of liver tissue and any damage might occur after being exposed to a certain

pharmacological agent such as STZ. Liver as an insulin-dependent tissue plays a vital

role in the metabolism of glucose and other substances. The damage of liver cells

cause a leakage of the contents out of the tissue into the blood stream (18). reported

that increased activities of serum AST, ALT and ALP level indicated that hepatic

dysfunction may be induced due to hyperglycemia in diabetic rats(19-20).

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