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<span style="font-size:15.0pt;mso-bidi-font-size: 14.0pt;font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:AR-SA; mso-bidi-font-weight:bold" lang="EN-US">Modulatory effects of <i>Azadirachta indica</i> leaf extract on cutaneous and hepatic biochemical status during promotion phase of DMBA/TPA-induced skin tumorigenesis in mice</span>

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Title Modulatory effects of Azadirachta indica leaf extract on cutaneous and hepatic biochemical status during promotion phase of DMBA/TPA-induced skin tumorigenesis in mice
 
Creator Arora, N
Bansal, M P
Koul, A
 
Subject Azadirachta indica
Dimethylbenz(a)anthracene
Phorbol-12-myristate-13-acetate
Xenobiotic biotransformation
Antioxidant defense system
 
Description 105-113
The modulation in biochemical
status of skin and hepatic tissue at the time point of commencement of
promotion stage of skin carcinogenesis in mice and its intervention with
aqueous Azadirachta indica leaf extract (AAILE) were investigated.
7,12-Dimethylbenz(a)anthracene (DMBA, 500 nmol/100 ul of acetone) was applied
topically for 2 weeks (twice weekly), followed by
phorbol-12-myristate-13-acetate (TPA, 1.7 nmol/100 ul) twice weekly for 6 weeks
on the depilated skin of mice and AAILE was administered orally at a dose level
of 300 mg/kg body wt thrice a week for 10 weeks. DMBA/TPA treatment upregulated
the phase I enzymes in skin and hepatic tissue, as revealed by the increased
cytochrome P450 (CYP) and cytochrome b5 (cyt b5) levels and aryl hydrocarbon
hydroxylase (AHH) activity when compared to the control group and
differentially modulated the activities of phase II enzymes like
glutathione-s-transferase (GST), DT-diaphorase (DTD) and uridine diphosphate
glucuronosyltransferase (UDP-GT). AAILE treatment decreased the
DMBA/TPA-induced increase in cutaneous CYP level and enhanced the DTD and
UDP-GT activities when compared with DMBA/TPA group. In the hepatic tissue of
AAILE + DMBA/TPA group, an increase in UDP-GT activity was observed when
compared to DMBA/TPA group. DMBA/TPA treatment did not alter the skin lipid
peroxidation (LPO) level when compared to control group, however, in the
animals that received AAILE treatment along with DMBA/TPA, a significant
increase in LPO was observed when compared to control group. This was
associated with a decrease in cutaneous reduced glutathione
(GSH) level of AAILE + DMBA/TPA group. Enhanced LPO level was observed in the
hepatic tissue of DMBA/TPA and AAILE + DMBA/TPA groups when compared to control
group. However, no alteration was observed in their hepatic
GSH levels. The micronuclei score in hepatic tissue did not exhibit significant
inter-group differences. The results of the present study suggest that apart
from skin, liver may be affected during DMBA/TPA-induced skin tumorigenesis.
AAILE treatment has the ability to modulate these changes potentially
influencing the process of tumor formation. These findings seem to be important
to carcinogenesis and its intervention with anti-cancer agents.


 
Date 2013-04-18T07:38:47Z
2013-04-18T07:38:47Z
2013-04
 
Type Article
 
Identifier 0975-0959 (Online); 0301-1208 (Print)
http://hdl.handle.net/123456789/17110
 
Language en_US
 
Rights CC Attribution-Noncommercial-No Derivative Works 2.5 India
 
Publisher NISCAIR-CSIR, India
 
Source IJBB Vol.50(2) [April 2013]