Research on Diabetes and hepatotoxicity in wistar rat By Nitin Kale final 24 june.pptx

Nitin R. Kale
M. Pharm 2ndYear
Department – Pharmacology
Rajarshi Shahu College of Pharmacy, Buldana
Preclinical Evaluation of Scopoletin Against Antitubercular
Drug-induced Hepatotoxicity in Type 2 Diabetes Mellitus
Experimental Model of Rats.
Guide Co-guide
Dr. S.P Jain Dr. S.P. Borikar

 Diabetes mellitus (DM) is metabolic disorders(1).
 DM is characterized by insulin deficiency and insulin resistance(2).
 According to the International Diabetes Federation (IDF), in 2019, 4.2 million deaths; and 463 million adults
aged between 20 and 79 years old were living with diabetes, It will rise up to 700 million by 2045.(3)
 India is “Diabetes Capital of the World (4)
 90% of diabetes mellitus cases are T2DM (3)(5).
 Liver is the “metabolic engine–room of the body”(9).
 Any liver damage or injury caused by drugs or chemicals is called hepatotoxicity(10),(6).
 T2DM represents a major risk factor for NAFLD with over 55% of persons living with T2DM being affected
by NAFLD(7).
 Main cause of hepatic injury, drugs like Acetaminophen, Carbon tetrachloride, INH & RIF which contain
toxic agents can also cause hepatocyte damage leading to liver injury(8),(11).
 The best-known hepatoxicity agents were INH and RIF(12,13).
INTRODUCTION
3/42

4/ 42
Tuberculosis is caused by the organisms Mycobacterium tuberculosis. According to WHO, In 2020, the South-
Fast Asian Region with 43% cases, African Region with 25% of cases and Western Pacific with 18% cases.
The dual burden of TB & DM has become a major public health concern. Prevalence of TB-
DM patients in Asia region-3.5%, Africa- 5.6%. North America-4.9%, Europe-1.82%.
DOT therapy includes 1 line drugs like Isoniazid & Rifampicin areused to treat
tuberculosis. This protocol produced a metabolicalteration in the liver, and due to this it
induced hepatotoxicity (
TB-DM comorbid patients may have a mortality of 2-5 times higher than
that of non-diabeticTB patients.
Tuberculosis
& Diabetes
mellitus
Comorbidity

 Scopoletin (6-methoxy-7-hydroxycoumarin) is found abundantly in variety of plants like noni,
carrot, grapefruit, and sweet potato and plays an important role in human health(14).
 Molecular weight 192 and a melting point of 204 – 206°C(15).
1.11 Drug profile
5/ 42
Fig.1.10: Structure of scopoletin (16)

6/ 42
(17) (18)
(19)
(20)
(21) (22)

 According to Abiodun Oyindamola O et al. (2022) studied TD2 in Wistar rats was induced with
nicotinamide/streptozotocin (NA/STZ). Serum glucose, lipid profiles, brain tumour necrosis factor alpha
(TNF-α) were determined. The Wistar rats were fasted overnight, subsequently TD2 was induced by
administering 110mg/kg NA intraperitoneally in physiological saline 15min prior to intravenous injection of
freshly prepared 65mg/kg STZ using 0.1mol/l (pH 4.5) cold citrate buffer(24).
 According to M. A. Buabeid et al. (2021) studied, observed and reported that antituberculosis drugs are
significantly cause hepatotoxicity, which varies from asymptomatic rise of the hepatic enzymes.
Hepatotoxicity was induced by INH + RIF (75+ 150 mg/kg) were dissolved in 1.5 ml distilled water to rats
individually once a day for a period of seven days for inducing hepatotoxicity(25).
Review of Literature
7/ 42

7. According to Srivastava R and K Sharma et al. (2008), studied, they were performed animal study, The
coexistence of tuberculosis and diabetes is common in patients who receive inadequate treatment. The risk of
hepatotoxicity from many toxicants is increased in diabetic rats. Silymarin provides protection against liver
injury caused by many hepatotoxicants, including antitubercular drugs (ATDs). In the wake of increased severity
of ATD-induced hepatotoxicity in diabetes they report that a study on the influence of diabetes on silymarin
hepatoprotection in rats.
Rats with diabetes induced via intraperitoneally injected streptozotocin (50 mg/kg), nondiabetic rats and
insulin-treated diabetic rats received [INH +RIFA + Pyrazinamide orally (p.o.)] with or without silymarin (100
mg/kg/day p.o.) treatment for 45 days. They studied and compared to nondiabetic rats, liver function tests and
histological changes of liver revealed exaggerated liver injury in diabetic rats caused by ATDs. These results
thus indicate that diabetes exaggerates ATD-induced liver injury and attenuates silymarin-induced
hepatoprotection(29).
Cont…
8/ 42

Aim:
To evaluate the hepatoprotective activity of Scopoletin against anti TB drug induce hepatotoxicity in diabetic
rats.
Objective:
Primary Objective
 This study aims to explore the potential of scopoletin as a therapeutic agent for managing diabetes and
protecting liver health.
 Evaluating the effects of scopoletin on glucose metabolism & Body weight
 Focuses on the human health benefits of bioactive dietary components with the aim of progression of
metabolic disorders.
Aim & Objective
9/ 42

Secondary Objective:
Assessing the impact of Scopoletin on liver enzyme levels, such as Alanine transaminase (ALT),
Aspartate transaminase (AST) and alkaline phosphatase(ALP), gamma-glutamyl transferase (GGT)
to determine the potential hepatoprotective effect.
 Investigating the influence of Scopoletin on oxidative stress markers, including malondialdehyde
(MDA), glutathione (GSH) and catalase, to evaluate its antioxidant properties and its ability
mitigate oxidative damage in the liver.
Cont..
10/ 42

Need of the study:
 Due to high cost, insufficient accessibility, severe adverse effects of synthetic drugs, and lack of
safety.
Synthetic antidiabetic drugs and antitubercular drugs associated with the more side effects and the
chronic toxicity that affect almost every organ system.
To obtain better therapeutic benefits and minor adverse reactions, these is pressing need for
antidiabetic drugs along with comorbidity from natural source.
The use of herbal formulation finds the way of curing diabetes mellitus and hepatotoxicity.
Need of Study & Plan of Work
11/ 42

Plan of work:
Literature survey
Collection of chemicals and materials
Procurement of animal as per the protocol
Procurement of test drug for the induction of diabetes like conditions in experimental animals
Induction of hepatotoxicity by using suitable chemical method (chemicals or inducers)
Cont..
12/ 42

To study the dose dependent effect of test drug on organ toxicity of diabetic rats
To study the dose dependent effect of test drug on the hepatotoxicity induced by inducer drug
Monitorization of physical parameter along with biological parameter in the presence of test drug / absent
of test drug
Evaluation of biochemical and antioxidant parameters Result evaluation by statistical analysis by using
graph pad Prism 8.0.2.
Cont..
13/ 42

Materials & Methods
14/ 42
Materials:
Animals: Wistar albino rats either sex (180-250 g) were used. Every procedure carried in the study
was authorized by IAEC& CPCSEA committee (1865/PO/Re/16/CPCSEA.19/02/2016).
Chemicals: Sr .No. Chemicals Manufacturer/ Supplier
01 Streptozotocin SRL (Sisco Research Lab)
02 Nicotinamide SRL (Sisco Research Lab)
03 Scopoletin Yucca Enterprises, Mumbai
04 Metformin RSCP, Buldana
05 Silymarin Yucca Enterprises, Mumbai
06 Isoniazid Vaibhav Chemicals, Ahamadnagar
07 Rifampicin Vaibhav Chemicals, Ahamadnagar
08 DTNB RSCP, Buldana
09 PBS RSCP, Buldana
10 Thiobarbituric acid RSCP, Buldana
11 Glacial acetic acid RSCP, Buldana
12 Hydrogen peroxide RSCP, Buldana

Pharmacological studies
a)STZ-NA induced Type 2 DM
The Wistar rats were starved for the whole night before having TD2 induced by giving 110 mg/kg of
NA intraperitoneally in physiological saline 15 minutes before giving them an intravenous injection
of freshly made 65 mg/kg STZ using 0.1mol/l (pH 4.5) cold citrate buffer. A non-fasting random
blood glucose test was conducted 72 hours after a STZ injection. The rats with blood glucose levels
greater than 250 mg/dl were considered diabetics and used for the study. For 28 days(30).
Cont..
17/ 42

18/ 42
STZ
Xanthine oxidase
Free radical generation
CH3 +
ꞵ-cell DNA damage
Methylation
H2O2
0-2
OH-2
PARP-1
Mechanism of action of Streptozotocin-Nicotinamide (31) (32) are following:
NICOTINAMIDE Intracellular NAD
ATP
ꞵ-Cell death
Necrosis & Apoptosis
Insulin synthesis

b) Induction of hepatotoxicity:
Hepatotoxicity was induced by INH + RIF (75+ 150 mg/kg) were dissolved in 1.5 ml distilled water
to rats individually once a day orally for a period of seven days for inducing hepatotoxicity(33).
Blood collection and preparation of serum:
 In the experimental study, all the animals were anesthetized; blood was collected by retro-orbital puncture
method; centrifuged at 10000 rpm for 10 min(34).
Preparation of liver homogenate:
 Animals were sacrificed by cervical dislocation and
 Liver tissues were separated, blotted dry, and then were divided into portions.
 The first portion was homogenized in PBS (phosphate buffered saline) solution, pH 7.4, centrifuged at
4,000 rpm for 15 min at 4 °C. The supernatant was removed for the assay of MDA, GSH and catalase(35).
Cont..
19/

Cont..
20/ 42
Oxidative stress parameter:
Glutathione, Catalase & Malondialdehyde (MDA):
The concentration of GSH, CAT & MDA
in the liver homogenate was measured according to the method described by Mohammad
Saidurrahman et al, (35).

Group =8
n=6 Total 48 rats
Group 1
Group 3
Group 2
Group 4
Group 5
Group 6
Group 7
Saline solution (0.9%)
STZ-NA (65-110mg/kg)
INH + RIFA (75+150mg/kg)
STZ-NA+INH+RIFA
STZ-NA+INH+RIFA +Test-1 SCOPOLETIN 5mg/kg (36)
STZ-NA+Anti-TB+Test-2 SCOPOLETIN 10mg/kg
STZ-NA+ Anti-TB +Metformin(300mg/kg) (37)
STZ-NA+ Anti-TB +Metformin+ Silymarin
(300+200mg/kg p.o.) (38)
Group 8
Experimental design
21/ 42

22/ 42
Day
1
Day 2 Day3 Day4 Day5 Day6 Day7 Day8 Day9 Day10 Day11 Day12 Day13 Day14 Day15
Day18 Day19 Day20 Day21 Day22 Day23 Day24 Day25 Day26 Day27 Day28
Blood sugar check by
Glucometer
INH+RIFA by ORAL
SCOPOLETIN treatment
Biochemical Parameter
Antioxidant Parameter
Note: Blood Glucose level &
Body weight measured on
every week
Day16
Day17
STZ-NA
Timeline

1 Effect of Scopoletin on the blood glucose level:
The blood glucose level was been measured during the protocol for every 7 days starting from 0th day.
Data expressed as mean ± SEM (n=6). Statistical comparison was done by two-way ANOVA followed by Tukey´s multiple
comparisons test; F=159.1, DFd=200, DFn=7. P<0.0001, **P<0.0061, ****P<0.0001. is considered statistically significant.
#P<0.0001, as compared to STZ-NTA; STZ-NTA+ Anti TB drug; The values in the parenthesis are dose in mg/kg.
23/ 42
Results & Discussion
day 0 day 7 day 14 day 21 day 28
0
100
200
300
400
Days
blood
glucose
level
(mg/dl)
CONTROL
STZ-NTA
INH-RIFA
STZ-NTA+INH-RIFA
SPL-1
SPL-2
MET
MET+SILY
***
****
****
#
*** ***

2. Effect of Scopoletin on body weight
The body weight was been measured during the protocol for every 7 days starting from 0th day.
Data expressed as mean ± SEM (n=6). Statistical comparison was done by ordinary Two-way ANOVA followed by comparison
test; F= 2.129, DFn=28, DFd=200. P< 0.0015 is considered statistically significant. *P<0.0476, #P<0.0007 as compared to STZ-
NTA and STZ-NTA+INH-RIFA this groups have shown significant decrease in the body weight. The values in the parenthesis are
dose in mg/kg.
24/ 42
Cont..
DAY 0 DAY 7 DAY 14 DAY 21 DAY 28
0
100
200
300
Days
body
weight(g)
CONTROL
STZ-NTA
INH-RIFA
STZ-NTA+INH-RIFA
SPL-1
SPL-2
MET
MET+SILY
***
*
***

3. Serum biochemical measurement: The levels of serum liver enzymes (AST, ALT, & ALP) were measured
by a Chemistry Analyzer (Bio Chemistry Coagulation Elisa Analyzer) using commercially available kits.
3.1 Effect of Scopoletin on ALT/ SGOT level in rats
Data expressed as mean ± SEM (n=6). one-way ANOVA followed by Tukey´s multiple comparisons test; F=1.112,
DFd=35, DFn=7. P<0.0001 is considered statistically significant. #P<0.0001 as compared to Control group and
*P<0.0476, ****P<0.0001, ***P<0.0007 and ****P<0.0001 as compared to STZ-NTA+ Anti TB drug group. SPL-
1(Scopoletin 5mg/kg), SPL-2(Scopoletin 10mg/kg), MET(Metformin), MET+SILY(Metformin+Silymarin): ALT:
Alanine aminotransferase, the values in the parenthesis are dose in mg/+kg.
25/ 42
Cont..
CONTROL
STZ-NTA
INH-RIFA
STZ-NTA+INH-RIFA
SPL-1
SPL-2
MET
MET+SILY
0
50
100
150
200
Groups
ALT
U/L
****
***
****
*
#

3.2 Effect of Scopoletin on AST/SGOT level in rats
Data expressed as mean ± SEM (n=6). one-way ANOVA followed by Dunnett's multiple comparisons test; F=21,
DFd=35, DFn=7, P<0.0001 is considered statistically significant. #P<0.0001 as compared to Control group and
*P<0.0476, **P<0.006, ****P<0.0001, and ****P<0.0001 as compared to STZ-NTA+INH-RIFA group. SPL-
2(Scopoletin 10mg/kg), MET(Metformin), MET+SILY (Metformin+ Silymarin): AST: Aspartate aminotransferase,
the values in the parenthesis are dose in mg/kg.
26/ 42
Cont…
CONTROL
STZ-NTA
INH-RIFA
STZ-NTA+INH-RIFA
SPL-1
SPL-2
MET
MET+SILY
0
20
40
60
80
Groups
AST
(U/L) ****
**
****
#

3.3 Effect of Scopoletin on ALP level in rats
*P<0.0476, **P<0.006, ****P<0.0001, and ****P<0.0001 as compared to STZ-NTA+INH-RIFA group. SPL-
2(Scopoletin 10mg/kg), MET(Metformin), MET+SILY (Metformin+ Silymarin): ALP: alkaline phosphatase. the
values in the parenthesis are dose in mg/kg.
27/ 42
Cont…
C
O
N
T
R
O
L
S
T
Z
-
N
T
A
I
N
H
-
R
I
F
A
S
T
Z
-
N
T
A
+
I
N
H
-
R
I
F
A
S
P
L
-
1
S
P
L
-
2
M
E
T
M
E
T
+
S
I
L
Y
0
100
200
300
Groups
ALP
(
IU/L)
****
****
****
***
#

3.4 Effect of Scopoletin on GGT level in rats
STZ-NTA+INH-RIFA group. SPL-2(Scopoletin 10mg/kg), MET(Metformin), MET+SILY (Metformin+ Silymarin):
GGT: gamma-glutamyl transferase. the values in the parenthesis are dose in mg/kg.
28/ 42
Cont…
CONTROL
STZ-NTA
INH-RIFA
STZ-NTA+INH-RIFA
SPL-1
SPL-2
MET
MET+SILY
0
50
100
150
Groups
GGT(IU/L)
****
****
****
****
#

4 Oxidative stress parameter
4.1 Effect of Scopoletin on GSH level in wistar rats
Data expressed as mean ± SEM (n=6). one-way ANOVA followed by Tukey´s multiple comparisons test; F=8.075,
DFd=40, DFn=7. P<0.0001 is considered statistically significant. ####P<0.0001 as compared to Control group and
*P<0.0187, **P<0.0074, **P<0.0010, as compared to STZ-NTA+INH-RIFA group. SPL2(Scopoletin10mg/kg),
MET(Metformin), MET+SILY (Metformin +Silymarin). GSH: Glutathione, the values in the parenthesis are dose in
mg/kg.
29/ 42
Cont…
CONTROL
STZ-NTA
INH-RIFA
STZ-NTA+INH-RIFA
SPL-1
SPL-2
MET
MET+SILY
0.0
0.5
1.0
1.5
2.0
Groups
GSH
(µmol/mg
protein
*#
*
** **

4.2 Effect of Scopoletin on Catalase level in wistar rats
Data expressed as mean ± SEM (n=6). one-way ANOVA followed by Dunnett's multiple comparisons test; F= 48.03,
DFd=40, DFn=7. P<0.0001 is considered statistically significant. ####P<0.0001 as compared to Control group and
*P<0.0117, ****P<0.0001, ****P<0.0001, ****P<0.0001as compared to STZ-NTA+INH-RIFA group. SPL-1
(Scopoletin5mg/kg): SPL2(Scopoletin10mg/kg), MET(Metformin), MET+SILY(Metformin+Silymarin). CAT: Catalase,
the values in the parenthesis are dose in mg/kg.
30/ 42
Cont…
C
O
N
T
R
O
L
S
T
Z
-
N
T
A
I
N
H
-
R
I
F
A
S
T
Z
-
N
T
A
+
I
N
H
-
R
I
F
A
S
P
L
-
1
S
P
L
-
2
M
E
T
M
E
T
+
S
I
L
Y
0.0
0.5
1.0
1.5
Groups
CAT(U/µg
Protein)
*
****
****
****
# # # #
# #

4.3 Effect of Scopoletin on LPO level in wistar rats.
Data expressed as mean ± SEM (n=6). Statistical comparison was done by one-way ANOVA followed by Tukey´s
multiple comparisons test; F=4.264, DFd=40, DFn=7. P<0.0013 is considered statistically significant. ##P<0.0011
as compared to Control group and *P<0.0213, **P<0.0144, **P<0.0019 as compared to STZ-NTA+INH-RIFA
group. SPL-1 (Scopoletin5mg/kg): SPL-2 (Scopoletin 10mg/kg), MET+SILY (Metformin +Silymarin), LPO
(Lipid Peroxidation). The values in the parenthesis are dose in mg/kg.
31/ 42
Cont…
CONTROL
STZ-NTA
INH-RIFA
STZ-NTA+INH-RIFA
SPL-1
SPL-2
MET
MET+SILY
0.0
0.5
1.0
1.5
2.0
Groups
LPO(µM/g
tissues)
**
##
*
**

32/ 42
Discussion
 Diabetes affects a lot of communities around the world.
 In 55–80% of diabetics, has been excessive glycogen deposition, fibrosis, cirrhosis, steatohepatitis,
and biliary disease in the liver patients(39).
 A significant amount of liver damage is induced by lipid peroxidation and other oxidative damages
like GSH, CAT which are caused by the hepatotoxic chemicals(40),(41).
 Then after SPL was given dose dependently in the same group of animals for last in 15 days (i.e.,
treatment started from day 17-28) at dose levels of 5 and 10 mg/kg p.o..
 Observed that the blood glucose levels were found to be significantly decreased in the SPL2 group
whereas SPL at low dose was failed to reduce the excessive blood glucose level.
 Therefore, from the above result SPL may consider as an antidiabetic potential. 5 mg/kg p.o. and
SPL at the dose of 10 mg/kg p.o. (59.14±5.10), (81.98±4.34) shows significantly decreased blood
glucose level as compared to disease control group.

33/ 42
Discussion
 Coexistence of tuberculosis and diabetes is common in patients who body weight get reduce(42).
 SPL has been shown the significant effect to restore the body weight,
 In previous study researcher found that the levels of serum liver enzymes (AST, ALT, ALP & GGT)
were measured by a Chemistry Analyzer.
 SPL-2(51.49 ± 9.0) show the more effect for reduction of ALT level than SPL-1(26.76 ± 9.03)
 The treatment of animals with Scopoletin at the dosage of 5 mg/kg groups for 28 days resulted in the
significant restoration of ALT level in the experimental animals.
 The SPL-2 shows a higher effect as compared to SPL-1, was found to be a decrease in AST level in
the experimental animals.
 SPL treatment group SPL 5 and 10mg/kg p.o. (38.67 ± 3.84) this treatment in rats shown the
significantly decrease level of GGT.

34/ 42
Discussion
 Oxidative stress parameters were evaluated. GSH, CAT, and LPO by using suitable methods.
 The MET treatment group and MET+SILY treated group also has shown the significant increase level of
GSH level in rats (1.005 ± 0.6677), (1.119 ± 0.7817) as compared to STZ-NTA+INH-RIFA treated group.
 Whereas, SPL has been shown the significant effect to restore the GSH level, but MET+ SILY group
shows more effect than lower dose and higher dose of SPL.
 The observed effect of SPL on GSH level at the dosage 10mg/kg were found to be significant.
 According to the H. Javdani et al, he reported that in hepatotoxic condition, the level of LPO was found to
be decrease(15);
 In our study, in disease conditions, increase in the level of LPO in the disease group.
 Whereas, in SPL2 shown reduction of elevated level of GSH.
 The observed effect of Scopoletin on GSH levels at the dosage of 10 mg/kg was found to be significant.
Hence, we predicted that the selected Test drug might have antioxidant potential was found to be
effective against to treat diabetes associated hepatotoxicity of Anti TB drug (Isoniazid & Rifampicin).

35/ 42
Conclusion
Conclusion
The main objective of this study was to critically evaluate the effect of test drug i.e. Scopoletin (6-methoxy-7-
hydroxycoumarin) in, the treatment of diabetes mellitus and its complications like hepatotoxicity induced by anti-tubercular
drugs in experimental animals.
After preclinical evaluation of different parameters such as blood glucose level, body weight, liver enzyme markers
(ALT, AST, ALP and GGT). Scopoletin decreased the tissue lipid peroxidation and increased the levels of antioxidant
enzymes like GSH, CAT and SOD in the liver tissues. These findings shows that Scopoletin can be used as a source of anti-
oxidant for the liver. Scopoletin showed hepatoprotective effect in Type-II DM comorbidity condition.
These estimated findings indicated that Scopoletin exhibited the protective effects against in anti-tubercular drug
induced hepatotoxicity in diabetic animals. This study could have the scope for further investigation to confirm the
molecular mechanism of Scopoletin for their effectiveness against Anti- TB drug such as INH-RIFA induced hepatotoxicity
in diabetic rats and will become promising therapy over to control and prevent the worsening of diabetes and associated co-
morbidities.

1. Mohamed J, Nazratun Nafizah AH, Zariyantey AH, Budin SB. Mechanisms of diabetes-induced liver damage: The role of
oxidative stress and inflammation. Sultan Qaboos Univ Med J. 2016;16(2):e132–41.
2. Subramani SK, Yadav D, Mishra M, Pakkirisamy U, Mathiyalagen P, Prasad GBKS. Prevalence of type 2 diabetes and
prediabetes in the gwalior-chambal region of central India. Int J Environ Res Public Health. 2019;16(23):1–12.
3. Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, et al. Pathophysiology of type 2
diabetes mellitus. Int J Mol Sci. 2020;21(17):1–34.
4. Devaki K, Beulah U, Akila G, Narmadha R, Gopalakrishnan VK. Bauhinia tomentosa L . on alloxan induced type 2
diabetes.
5. Joshi SR. Diabetes Care in India. Ann Glob Heal [Internet]. 2015;81(6):830–8. Available from:
http://dx.doi.org/10.1016/j.aogh.2016.01.002
6. Goboza M, Aboua YG, Chegou N, Oguntibeju OO. Biomedicine & Pharmacotherapy Vindoline effectively ameliorated
diabetes-induced hepatotoxicity by docking oxidative stress , inflammation and hypertriglyceridemia in type 2 diabetes-
induced male Wistar rats. Biomed Pharmacother [Internet]. 2019;112(January):108638. Available from:
https://doi.org/10.1016/j.biopha.2019.108638
7. Sayeli VK, Shenoy AK. Antidiabetic effect of bio-enhanced preparation of turmeric in streptozotocin-nicotinamide induced
type 2 diabetic Wistar rats. J Ayurveda Integr Med [Internet]. 2021;12(3):474–9. Available from:
https://doi.org/10.1016/j.jaim.2021.04.010
8. Goboza M, Aboua YG, Chegou N, Oguntibeju OO. Vindoline effectively ameliorated diabetes-induced hepatotoxicity by
docking oxidative stress, inflammation and hypertriglyceridemia in type 2 diabetes-induced male Wistar rats. Biomed
Pharmacother [Internet]. 2019;112(January):108638. Available from: https://doi.org/10.1016/j.biopha.2019.108638
36/ 42
References

9. Palliyaguru DL, Shiroma EJ, Nam JK, Duregon E, Teixeira VL, Price NL, et al. translation. 2022;33(11):2189–200.
10. Wali A. Amelioration of Rifampicin and Isoniazid Induced Liver Oxidative Damage and Inflammation Response by
Propolis Ex ... Amelioration of Rifampicin and Isoniazid Induced.
11. Willatts SM. The liver. Curr Anaesth Crit Care. 1990;1(4):195.
12. Su Q, Kuang W, Hao W, Liang J, Wu L, Tang C, et al. Antituberculosis Drugs (Rifampicin and Isoniazid) Induce Liver
Injury by Regulating NLRP3 Inflammasomes. Mediators Inflamm. 2021;2021.
13. Srivastava RK, Sharma S, Verma S, Arora B, Lal H. Influence of diabetes on liver injury induced by antitubercular drugs
and on silymarin hepatoprotection in rats. Methods Find Exp Clin Pharmacol [Internet]. 2008 Dec;30(10):731—737.
Available from: https://doi.org/10.1358/mf.2008.30.10.1316824
14. Hassan HM, Guo HL, Yousef BA, Luyong Z, Zhenzhou J. Hepatotoxicity mechanisms of isoniazid: A mini-review. J Appl
Toxicol. 2015;35(12):1427–32.
15. Napiroon T, Bacher M, Balslev H, Tawaitakham K, Santimaleeworagun W. Scopoletin from Lasianthus lucidus Blume (
Rubiaceae ): A potential antimicrobial against multidrug-resistant Pseudomonas aeruginosa. 2018;8(09):1–6.
16. Hassan HM, Guo HL, Yousef BA, Luyong Z, Zhenzhou J. Hepatotoxicity mechanisms of isoniazid: A mini-review. J Appl
Toxicol. 2015;35(12):1427–32.
17. Antika LD, Hikmat H, Septama AW. Scopoletin : a review of its source , biosynthesis , methods of extraction , and
pharmacological activities. 2022;77:303–16.
18. Kalpana K, Priyadarshini E, Sreeja S, Jagan K. Scopoletin intervention in pancreatic endoplasmic reticulum stress
induced by lipotoxicity. 2018;94.
Cont..
37/ 42

19. Zhang W, Zhao W, Ge C, Li X, Sun Z. Scopoletin Attenuates Intracerebral Hemorrhage-Induced Brain Injury and
Improves Neurological Performance in Rats. 2021;74–81.
20. Antika LD, Hikmat H, Septama AW. Scopoletin : a review of its source , biosynthesis , methods of extraction , and
pharmacological activities. 2022;77:303–16.
21. Lee EJ, Na W, Kang MK, Kim YH, Kim DY, Oh H, et al. Hydroxycoumarin scopoletin inhibits bone loss through
enhancing induction of bone turnover markers in a mouse model of type 2 diabetes. Biomedicines. 2021;9(6).
22. Napiroon T, Bacher M, Balslev H, Tawaitakham K, Santimaleeworagun W. Scopoletin from Lasianthus lucidus Blume (
Rubiaceae ): A potential antimicrobial against multidrug-resistant Pseudomonas aeruginosa. 2018;8(09):1–6.
23. Mohamed J, Nazratun Nafizah AH, Zariyantey AH, Budin SB. Mechanisms of diabetes-induced liver damage: The role of
oxidative stress and inflammation. Sultan Qaboos Univ Med J. 2016;16(2):e132–41.
24. Phatak RS, Khanwelkar CC, Matule SM, Datkhile KD, Hendre AS. Antihyperlipidemic Activity of Murraya koenigii
Leaves Methanolic and Aqueous Extracts on Serum Lipid Profile of High Fat-Fructose Fed Rats. 2019;11(4):836–41.
25. Diamante G, Cely I, Zamora Z, Ding J, Blencowe M, Lang J, et al. Systems toxicogenomics of prenatal low-dose BPA
exposure on liver metabolic pathways, gut microbiota, and metabolic health in mice. Environ Int. 2021;146.
38/ 42
Cont..

26. Drayton DJ, Birch RJ, D’Souza-Ferrer C, Ayres M, Howell SJ, Ajjan RA. Diabetes mellitus and perioperative outcomes: a
scoping review of the literature. Br J Anaesth [Internet]. 2022;128(5):817–28. Available from:
https://doi.org/10.1016/j.bja.2022.02.013
27. Willatts SM. The liver. Curr Anaesth Crit Care. 1990;1(4):195.
28. Anderson P, Grills N, Singh R, Singh R, Evans RG, Sengupta P, et al. Prevalence of diabetes and pre-diabetes in rural
Tehri Garhwal, India: Influence of diagnostic method. BMC Public Health. 2019;19(1):1–8.
29. Srivastava RK, Sharma S, Verma S, Arora B, Lal H. Influence of diabetes on liver injury induced by antitubercular drugs
and on silymarin hepatoprotection in rats. Methods Find Exp Clin Pharmacol [Internet]. 2008 Dec;30(10):731—737.
Available from: https://doi.org/10.1358/mf.2008.30.10.1316824
30. Phatak RS, Khanwelkar CC, Matule SM, Datkhile KD, Hendre AS. Antihyperlipidemic Activity of Murraya koenigii
Leaves Methanolic and Aqueous Extracts on Serum Lipid Profile of High Fat-Fructose Fed Rats. 2019;11(4):836–41.
32. Palliyaguru DL, Shiroma EJ, Nam JK, Duregon E, Teixeira VL, Price NL, et al. translation. 2022;33(11):2189–200.
39/ 42
Cont..

33. Diamante G, Cely I, Zamora Z, Ding J, Blencowe M, Lang J, et al. Systems toxicogenomics of prenatal low-dose BPA
exposure on liver metabolic pathways, gut microbiota, and metabolic health in mice. Environ Int. 2021;146.
34. Newton KP, Wilson LA, Crimmins NA, Fishbein MH, Molleston JP, Xanthakos SA, et al. Incidence of Type 2 Diabetes in
Children With Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol. 2022;1261–70
35. Sharma S, Anand A, Bhatia A, Sharma V, Singh AK, Banerjee D, Patil AN. Pharmacological Evaluation of Scopoletin in
the Carbon Tetrachloride-Induced Hepatotoxicity Model in Wistar Rats. J Pharm Bioallied Sci. 2022 Oct-Dec;14(4):201-
206. doi: 10.4103/jpbs.jpbs_333_22. Epub 2023 Feb 17. PMID: 37051421; PMCID: PMC10084995.
36. Sharma S, Anand A, Bhatia A, Sharma V, Singh AK, Banerjee D, Patil AN. Pharmacological Evaluation of Scopoletin in
the Carbon Tetrachloride-Induced Hepatotoxicity Model in Wistar Rats. J Pharm Bioallied Sci. 2022 Oct-Dec;14(4):201-
206. doi: 10.4103/jpbs.jpbs_333_22. Epub 2023 Feb 17. PMID: 37051421; PMCID: PMC10084995.
37. M.; Markova, I.; Miklankova, D.; Zapletalova, I.; Poruba, M.; Racova, Z.; Vecera, R.; Malinska, H. The Beneficial
Additive Effect of Silymarin in Metformin Therapy of Liver Steatosis in a Pre-Diabetic Model. Pharmaceutics 2022, 14,
45. https://doi.org/ 10.3390/pharmaceutics14010045
38. Vangaveti S, Das P, Kumar VL. Metformin and silymarin afford protectionin cyclosporine A induced hepatorenal toxicity
in rat by modulating redox status and inflammation. J Biochem Mol Toxicol. 2021 Jan;35(1):e22614. doi:
10.1002/jbt.22614. Epub 2020 Sep 4. PMID: 32886845.
40/ 42
Cont..

39. Darenskaya MA, Kolesnikova LI, Kolesnikov SI. Oxidative Stress: Pathogenetic Role in Diabetes Mellitus and Its
Complications and Therapeutic Approaches to Correction. Bull Exp Biol Med. 2021;171(2):179–89.
40. Lee EJ, Na W, Kang MK, Kim YH, Kim DY, Oh H, et al. Hydroxycoumarin scopoletin inhibits bone loss through
enhancing induction of bone turnover markers in a mouse model of type 2 diabetes. Biomedicines. 2021;9(6).
42. Su Q, Kuang W, Hao W, Liang J, Wu L, Tang C, et al. Antituberculosis Drugs (Rifampicin and Isoniazid) Induce Liver
Injury by Regulating NLRP3 Inflammasomes. Mediators Inflamm. 2021;2021.
41/ 42
Cont..

Research on Diabetes and hepatotoxicity in wistar rat By Nitin Kale final 24 june.pptx

Recommended

Recommended

More Related Content

Similar to Research on Diabetes and hepatotoxicity in wistar rat By Nitin Kale final 24 june.pptx

Similar to Research on Diabetes and hepatotoxicity in wistar rat By Nitin Kale final 24 june.pptx (20)

More from NitinKale46

More from NitinKale46 (6)

Recently uploaded

Recently uploaded (20)

Research on Diabetes and hepatotoxicity in wistar rat By Nitin Kale final 24 june.pptx