BUKU ABSTRAK - Universiti Putra Malaysia

Apoptotic Cell Death in the Mechanism of Hepatotoxicity induced by Azole
Antifungal Drug Itraconazole
Assoc. Prof. Dr. Muhammad Nazrul Hakim Abdullah
Soo Li Chin, Azhar Yaacob, Zuraini Ahmad, Mohd. Roslan Sulaiman and Zainul Amiruddin Zakaria
Sports Academy, University Putra Malaysia,
43400 UPM Serdang, Selangor, Malaysia.
+603-8946 4277; nazrul.hakim@gmail.com
Itraconazole is an orally active, broad-spectrum, triazole antifungal agent has a broad spectrum of activity
and it is used for treatment of diseases such as vaginal candidiasis, dermatomycosis, onychomycosis, and several
deep mycoses. Itraconazole acts by inhibiting biosynthesis of ergosterol, which is an essential component of
fungal cell membranes. The drug blocks the formation of ergosterol from lanosterol causing membrane leakage
and gradual cell death. This study is conducted to investigate the hepatotoxicity and nephrotoxicity of itraconazole
in rats’ hepatocytes. 40 rats are divided into two groups: single dose and repeated dose groups. The single dose
group is further divided into four, according to the concentration of drug given: 0, 10, 100 and 200 mg/kg. The
repeated dose is also divided into four: 0, 10, 50 and 100 mg/kg/day for 14 days. The rats are then sacrificed
24 hrs after the last dose and their livers and kidneys removed for histology examination, electron microscopy
and immunohistochemistry examination, which is the expression of apoptotic protein Bax and anti-apoptotic
protein Bcl-2. Dose-dependent hepatocellular necrosis, focal necrosis, periportal degeneration, glomerular
nephritis and severe inflammation in the hepatocytes and in the capsules were observed from the liver and
kidney in histology examination from repeated dose group. From electron microscopy examination, incomplete
or total loss of mitochondria cristae and distorted membrane nucleus was found, indicating cell apoptosis. In
immunohistochemistry examination, Bax protein was found to be up-regulated and Bcl-2 protein down-regulated,
which also indicates cell apoptosis. In the single dose group, mild degenerative changes and mild inflammation in
the hepatocytes and kidney were observed in the rats with higher dose. These results demonstrated that antifungal
drug itraconazole will cause organ toxicity and the level of hepatotoxicity and nephrotoxicity severity increases
with the increase of dose concentration injected and longer exposure time to the drug.
Keywords: Itraconazole, apoptotic, hepatotoxicity, azole, nephrotoxicity
Protective Effect of Bauhinia purpurea Leaf Extracts against Indomethacin-induced
Gastric Ulcers in Rats
Assoc. Prof. Dr. Zainul Amiruddin Zakaria
Elly Ezlinda Abdul Hisam, Mohd. Salleh Rofiee, Muhammad Nazrul Somchit, Zuraini Ahmad, Mohd. Roslan
Sulaiman, Teh Lay Kek and Mohd. Zaki Salleh
Faculty of Medicine and Health Sciences, University Putra Malaysia,
43400 UPM Serdang, Selangor, Malaysia.
603-8947 2654; zaz@medic.upm.edu.my
Previous study has demonstrated the potential of Bauhinia purpurea leaf extracts to produce gastroprotective
effect against ethanol, a necrotizing agent. In order to establish B. purpurea gastroprotective profile, the present
study was carried out to determine the gastroprotective effect of various extracts of B. purpurea leaves against
indomethacin-induced gastroduodenal ulcer. The animals were given (orally) distilled water, 8% Tween 80 or
normal saline as negative controls; or, aqueous, chloroform and methanol leaf extracts of B. purpurea (100, 500
and 1000 mg/kg) followed 30 min later with oral administration of indomethacin (100 mg/kg) to induce gastric
ulcer. Four hours after indomethacin administration, the animals were sacrificed and the stomachs were collected
for examination. Based on the dose administered, pre-treatment with aqueous extract exerted 63.5%, 54.8% and
39.1% of ulcer inhibition, respectively. The chloroform extracts showed 31.3%, 22.9% and 29.2% while methanol
extracts exhibited 31.6%, 50.5% and 47.4% reduction in lesions as compared to their respective negative controls.
Omeprazole (30 mg/kg) served as the positive control for this study. All extracts exhibited gastroprotective activity
with the aqueous extract being the most effective one and, thus, requires further extensive study.
Keywords: Bauhinia purpurea, leaves, various extracts, ethanol-induced gastric ulcer, antiulcer
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