Protective effect of andrographolides against docetaxel-induced cognitive impairment in rats bearing mammary tumours
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1
Putra Malaysia University, Malaysia
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2
Royal College of Surgeons in Ireland, Ireland
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3
University Malaya Medical Centre, Malaysia
Background
Andrographolide (AGP) and 14-deoxy-11,12-didehydroandrographolide (DDAG) are two main diterpenoid constituents of Andrographis paniculata, which have shown several therapeutic effects. The aim of this study was to examine the protective effects of AGP and DDAG against cognitive impairment (CICI) caused by chemotherapeutic agent, docetaxel (DTX), on rats with mammary tumours.
Methods
A two-day Morris Water Maze (MWM) protocol, which involved training with a visible platform on day one followed by testing with a hidden platform on day two, was performed. Ten groups of female Sprague Dawley rats were used. The rats were injected with LA7 cells into the mammary gland pad to form tumours and further divided into groups of normal control (NC), cancer control (CC), treatment with DTX (single dose 5 mg/kg i.p.), three doses (0.25, 0.50 and 1.0 mg/kg) of AGP or DDAG and a vehicle. Subsequently, AGP, DDAG or vehicle was administered intraperitoneally for seven consecutive days followed by DTX injection after day one of visible platform trial. Levels of pro-inflammatory cytokine interleukin IL-1, lipid peroxidation marker (thiobarbituric acid-reactive substances (TBARS) and reactive oxygen species (ROS)) were measured.
Results
After 24 hours of DTX injection, the escape latency of DTX had significantly (p<0.001) increased to 58.1 sec compared to 24.7 sec in CC. AGP and DDAG significantly (p<0.001) reduced this DTX-induced latency to about 10-16 sec. AGP and DDAG significantly (p<0.001) reduced the elevated IL-1β (78-91%), IL-6 (55-75%), TNF-α (63-73%), TBARS (52-83%) and ROS (22-50%) levels when compared to DTX. AGP and DDAG did not affect the anti-cancer activity of DTX.
Conclusion
AGP and DDAG, if given prior to DTX, may be protective against the chemotherapy-induced cognitive impairment.
Acknowledgements
The authors acknowledge the Ministry of Agriculture and Agro-Based Industry Malaysia for funding this research (NRGS Grants NH1014D025).
Keywords:
AGP,
DDAG,
DOCETAXEL,
Morris water maze,
cognitive impairment
Conference:
International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18)
“Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019.
Presentation Type:
Poster Presentation
Topic:
Neurodegenerative diseases
Citation:
Khatab
NI,
Sani
D,
Kirby
BP,
Muhtarrudin
N,
Fuang
HG,
Stanslas
J and
Basri
H
(2019). Protective effect of andrographolides against docetaxel-induced cognitive impairment in rats bearing mammary tumours.
Front. Pharmacol.
Conference Abstract:
International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18)
“Seizing Opportunities and Addressing Challenges of Precision Medicine”.
doi: 10.3389/conf.fphar.2018.63.00134
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Received:
12 Oct 2018;
Published Online:
17 Jan 2019.
*
Correspondence:
Prof. Johnson Stanslas, Putra Malaysia University, Seri Kembangan, Malaysia, jstanslas@yahoo.co.uk
Prof. Hamidon Basri, Putra Malaysia University, Seri Kembangan, Malaysia, hamidonbasri@gmail.com