1.0 TEST SYSTEM DETAILS:
Species : Rattus
norvegicus (Rat)
Strain : Wistar or Sprague Dawley
Age : 8-10 weeks
Body Wight : 120-200 g
Sex : Male
No. of animals : 10 /Group
Total Animals : 10×6= 60
2.0 ALLOCATION OF GROUPS:
Model
- CARDIOTOXICITY AND NEPHROTOXICITY
|
Groups |
Treatment |
Dose; ROA |
No. of Animals |
|
G1 |
Normal
Control |
Normal
saline or 0.25% Na-CMC |
10 |
|
G2 |
Normal
Control+ Herbal extract 1st Dose |
X mg/kg; p.o. |
10 |
|
G3 |
Normal
Control+ Herbal extract 2nd Dose |
XX mg/kg; p.o. |
10 |
|
G4 |
Adriamycine
|
15
mg / kg; p.o. |
10 |
|
G5 |
Adriamycine
(15 mg / kg) + Herbal extract 1st Dose |
X
mg/kg; p.o. |
10 |
|
|
(Adriamycine
(15 mg / kg) + Herbal extract 2nd Dose |
XX
mg/kg; p.o. |
10 |
*The
doses and ROA (Routes of administration) will be decided based on the type of reference
/Inducing drug.
3.0 METHOD:
·
Group
- 1, 3, 5 and 6 pretreated with Herbal extract
orally for 7 days. On the 7th day adriamycin is injected intra
peritoneal to 4, 5, 6, groups of animals.
·
On
the 10th day, six animals from each group will be used for the
evaluation of ECG and subjected to decapitation.
·
Blood
samples and heart specimens were collected for the estimation of various
biomarkers in serum as will as heart.
·
Formalin
fixed heart specimens were used for histopathological examination.
·
Similarly
the above group of the remaining six animals daily treated with herbal extract
for 30 days, after administration of adriamycin injection.
·
Animals
will be subjected to decapitation, Blood samples and kidney specimens are collected
for the estimation of various biomarkers in serum as will as kidney. Formalin
fixed heart specimens were used for histopathological examination.
4.0 END POINT PARAMETER(S):
·
Clinical observation
·
Feed water consumption
·
Body Weight.
·
The heart and kidney will
be isolated, weighed
· Blood serum parameters: Serum
glutamic pyruvic transaminase (SGPT), Serum glutamic oxoleacetic
transaminase.(SGOT), Lactate dehyrogenase (LDH), Creatinine phosphokinase(CPK),
Serum urea, Total Protein / Albumin Concentration determination.
·
Electro
cardiac changes.
·
Antioxidant-activity-
SOD, GSH-px & Catalase level
·
Histopathology of Heart
and Kidney tissues.
5.0 MOA : Adriamycin –
induced cardio toxicity and nephrotoxicity have been supposed to be mediated
through different mechanism like inducing semiquinone free radical formation, ion
dependent oxidative damage to biological macromolecules and membrane lipid
peroxidation. Tissue with less developed activities of anti- oxidant enzymes
like super oxide dismutase (SOD), catalase (CAT) and glutathione peroxide (GHS-px)
have been reported in adriamycin induced cardiac and nephrotoxicity.
7.0 REFERENCE(S):
7.1 Karthick M, Stanely Mainzen Prince P. Protactive
effect of rutin, a bioflavonoid on lipid peroxides and antioxidants in isoproterenol-induced
myocardial infarction in rats. Journal of Pharmacy and Pharmacology 2006; 58:
701-707.
7.2 Rajakannu
S, Surinderkumar Y, Arunachalam G and Devaki T. Protective effect of
nardostachys jatamansi on oxidative injury and cellular abnormalities during
doxorubicin induced cardiac damage in rats. Journal of Pharmacy and
Pharmacology 2006; 58: 257-62.
7.3 Murat
Y, Hasan E, Mustafa I, Ersin F. Caffeic
acid phenethyl ester as a protective agent against doxorubicin nephrotoxicity
in rats. Clinica Chimica Acta 2004; 348: 27-34
7.4 Narayanan
V, Durairaj P and Venkatesan A. Curcumin prevents adriamycin nephrotoxicity in
rats. British Journal of Pharmacology 2000; 129: 231-34.
7.5 Rade
I, Marija B, Martina P, Borut S. Acute doxorubicin nephrotoxicity in rats with malignant
neoplasma can be successfully treated with fullerenol C60(OH)24
via suppression of oxidative stress.
Pharmacological Reports 2008; 60: 742-749.
7.6 Karim S, Bhandari U, Kumar H, Pillai KK. Doxorubicin
Induced Cardio toxicity and Modulation by Drugs. Indian Journal of Pharmacology
2001; 33: 203-07.
7.7 Nagla
A, Shitany El, Sahar El- H. Silymarin prevents adriamycin-induced cardio
toxicity and nephrotoxicity in rats. Food and Chemical Toxicology 2008; 46: 2422-2428.
7.8 Chularojmontri
Linda, Suvara Kimnite, Wattanapitayakul, Angkana Herunsalee, Suphan
Charuchongkolgwongse. Antioxidant and cardio protective effects of phyllanthus
Urinaria Linn. On Doxorubicin- induced cardiotoxicity. Biol. Pharm. Bull 2005;
28(7):1165-1171.
7.9 Gnanapragasam
A, Yogeeta S, Subhashini R, Ebenezar KK, Satish V, Devaki T. Adriamycin induced
myocardial failure in rats: Protective role of Centella Asiatica. Mol. And
cell. Biochem 2007; 294: 55-63.
Hi. I’m Writer of Researchsop.com. ’ ’ Please share these SOPs to all concern pharma people for their development. I like to fullfill the need of curious people. These things inspire me to make things looks better.
0 comments:
Post a Comment