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Title:	The effects of polysaccharide extract of psidium guajava (guava) fruit on paracetamol-induced liver toxicity
Authors:	Dr. Aspalilah Binti Alias (P62372)
Supervisor:	Farida Hussan, Assoc. Prof. Dr.
Keywords:	Psidium guajava Liver Dissertations, Academic -- Malaysia
Issue Date:	27-Mar-2014
Description:	Liver is a target organ of drug toxicity because of its major role in metabolism and detoxification. The toxic dose of paracetamol (PCM) is frequently used to induce liver toxicity for experimental purposes. Some plant extracts with antioxidant activity possess hepatoprotective effect. The present study was aimed to evaluate the role of polysaccharide extract from Psidium guajava fruit (PPG) on PCM-induced liver toxicity in male rats. The component of PPG was determined using high-performance liquid chromatography (HPLC) and ultraviolet (UV)-visible spectrophotometry. The impact of daily dosing of PPG was assessed using histopathological and biochemical indices. Thirty-eight male Sprague Dawley rats were divided into two groups which were normal control group and PCM-induced group. The normal control group was further subdivided into normal saline and 400 mg/kg PPG supplementation group. The PCM group was divided into normal saline, 200 mg/kg and 400 mg/kg PPG-supplemented groups. The PPG was given orally for 14 days which was followed by induction of PCM (2 g/kg) on day 15. Blood was collected from the retro-orbital sinus 24 hours after PCM induction and serum was analysed for liver function test. Liver tissues were taken and homogenised for pro-inflammatory cytokines [interleukin 6 (IL-6) and tumour necrosis factor--α(TNF--α)], antioxidant enzymes and histological studies. HPLC result showed that PPG was mainly composed of galacturonic acid, galactose, glucose, xylose, mannose and rhamnose. Liver enzymes (AST and ALT) increased significantly after induction with PCM (p<0.05). However, after administration of PPG, the levels of these enzymes were restored in a dose-dependent manner. The TNF--α and IL-6 were significantly increased (p<0.05) in the PCM group compared to the normal group. However, the PPG supplementation in PCM groups significantly reduced the levels of TNF-α and IL-6 when compared to the PCM group. There was a significant decrease in the levels of antioxidant enzymes in the PCM group compared to the normal group while a significant increase in the antioxidant enzymes (p<0.05) of the PCM group with PPG supplementation. Normal architecture of hepatocellular cords with the sinusoidal spaces was observed in the liver of the normal control groups. The liver of the PCM group without PPG revealed packed hepatocellular cords around the central vein with narrow sinusoidal spaces. There were also a few binucleated hepatocytes which indicated features of cellular necrosis. Glycogen depletion was detected in the PCM group as shown with PAS staining. However, the extent of depletion was reduced by the PPG supplementation. In conclusion, it is shown that PPG has antioxidant and hepatoprotective properties towards PCM-induced liver toxicity, suggesting that it has a potential to use as a supplementation to protect against liver injury.,Hepar adalah organ sasaran ketoksikan dadah kerana peranan utamanya dalam metabolisme dan detoksifikasi. Dos toksik parasetamol (PCM) sering digunakan untuk mendorong ketoksikan hepar untuk tujuan eksperimen. Beberapa ekstrak tumbuhan dengan aktiviti antioksidan mempunyai kesan pelindung hepar. Kajian ini bertujuan untuk menilai peranan ekstrak polisakarida daripada buah Psidium guajava (PPG) disebabkan ketoksikan hepar aruhan PCM dalam tikus jantan. Komponen PPG telah ditentukan dengan menggunakan kromatografi prestasi tinggi cecair (HPLC) dan spektrofotometri penglihatan ultraungu (UV). Kesan dos harian PPG telah dinilai dengan menggunakan indeks histopatologi dan biokimia. Tiga puluh lapan ekor tikus jantan Sprague Dawley telah dibahagikan kepada dua kumpulan iaitu kumpulan kawalan normal dan kumpulan parasetamol teraruh. Kumpulan kawalan normal telah dibahagikan lagi kepada kumpulan salina normal dan kumpulan 400 mg/kg suplemen PPG. Kumpulan PCM telah dibahagikan kepada kumpulan salina normal, kumpulan 200 mg/kg dan kumpulan 400 mg/kg suplemen PPG. PPG telah diberikan secara oral selama 14 hari yang diikuti oleh induksi PCM (2 g/kg) pada hari ke 15. Darah diambil dari sinus retro-orbit 24 jam selepas induksi PCM dan serum telah dianalisa untuk ujian fungsi hati. Tisu hati telah diambil dan dihomogenkan untuk sitokin proinflamasi [interleukin 6 (IL-6) dan faktor nekrosis tumor-α (TNF-α)], enzim antioksidan dan kajian histologi. Hasil HPLC menunjukkan bahawa PPG terutamanya terdiri daripada asid galakturonik, galaktosa, glukosa, xilosa, manosa dan ramnosa. Enzim hepar (AST dan ALT) meningkat secara signifikan selepas induksi dengan PCM (p<0.05). Walau bagaimanapun, selepas pengambilan PPG, aras enzim ini telah dipulihkan secara bergantung dos. TNF-α dan IL-6 telah meningkat dengan signifikan (p<0.05) dalam kumpulan PCM berbanding kumpulan normal. Walau bagaimanapun, suplementasi PPG dalam kumpulan PCM mengurangkan aras TNF-α dan IL-6 jika dibandingkan dengan kumpulan PCM. Terdapat pengurangan yang signifikan dalam aras antioksidan enzim dalam kumpulan PCM berbanding kumpulan yang normal manakala peningkatan yang signifikan dalam aras enzim antioksidan (p<0.05) dalam kumpulan PCM dengan suplemen PPG. Struktur korda hepatosel dengan ruang sinus yang normal diperhatikan dalam hepar kumpulan kawalan normal. Hepar kumpulan PCM tanpa PPG menunjukkan korda hepatosel padat mengelilingi vena sentral dengan ruang sinus yang sempit. Terdapat juga beberapa hepatosit dwinukleus yang menunjukkan ciri-ciri nekrosis sel. Kekurangan glikogen dikesan dalam kumpulan PCM seperti yang ditunjukkan dengan pewarnaan PAS. Walau bagaimanapun, pengurangan ini diatasi dengan suplemen PPG. Kesimpulannya ia menunjukkan bahawa PPG mempunyai ciri-ciri antioksidan dan kesan pelindung hepar terhadap ketoksikan aruhan PCM, lalu mencadangkan bahawa PPG mempunyai potensi sebagai suplemen untuk melindungi hepar daripada kecederaan hati.,Master
Pages:	112
Publisher:	UKM, Kuala Lumpur
Appears in Collections:	Faculty of Medicine / Fakulti Perubatan

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