Sains Malaysiana 51(11)(2022):
3755-3764
Effectuation of Pleurotus pulmonarius on Hypercholesterolemic Wistar-Kyoto Rats: Analysis on Liver and
Sera
(Kesan Pleurotus pulmonarius terhadap Tikus Wistar-Kyoto Hiperkolesterolemik: Analisis ke atas Hati dan Sera)
NOOR
FAZILA MOHD YAHAYA, NORHANIZA AMINUDIN* & NOORLIDAH ABDULLAH
Mushroom Research Centre,
Institute of Biological Sciences, Faculty of Science, Universiti Malaya, 50603 Kuala Lumpur, Federal Territory, Malaysia
Diserahkan: 30 September 2021/Diterima: 20 Jun 2022
Abstract
Hypercholesterolemia is one of the potential risks
of cardiovascular heart disease (CHD). An early diagnosis and treatment
attenuate the risk of CHD. Besides statin prescription for
hypercholesterolemia, functional food has an added value to ameliorate the
risk. This study was conducted to analyse the significant effect of grey oyster
mushroom (Pleurotus pulmonarius)
on hypercholesterolemia. Thirty-six Wistar-Kyoto rats
were assigned into six groups, consisted of normal (N), hypercholesterolemia
(H), two groups for prevention (P1 and P2), and two groups for treatment (T1
and T2). For prevention purpose, P1 and P2 were concomitantly induced to be hypercholesterolemic and fed with either crude aqueous
extract of P. pulmonarius (CA) or simvastatin for 45 days. Following 45 days of hypercholesterolemic-induction,
T1 and T2 rats were then orally fed with either CA or simvastatin for another
30 days. On day 45, groups N, H, P1, and P2 were sacrificed, whereas groups T1
and T2 were sacrificed on day 75. Histopathology examination showed the
conditions of liver tissues. Fat droplets were observed in hypercholesterolemic hepatic tissues and were also remained in the hepatic tissues of rats belonged
to the treatment groups. The tissues’ viability was better in prevention groups
suggesting the compound(s) present in CA might be able to protect them from
further damage. Metabolomic analysis of the sera from
P1 and T1 rats showed altered regulation of several metabolites such as
pantothenic acid, N-carbamylglutamate, serotonin and
ceramide against the control group.
Keywords: Hepatic cells; histopathology;
hypercholesterolemia; metabolomic
Abstrak
Hiperkolesterolemia adalah salah satu potensi
risiko penyakit jantung kardiovaskular (CVD). Diagnosis dan rawatan awal
mengurangkan risiko CVD. Selain statin untuk merawat hiperkolesterolemia,
makanan berfungsi mempunyai nilai tambah untuk mengurangkan risiko. Kajian ini
dilakukan untuk menganalisis pengaruh signifikan cendawan tiram kelabu (Pleurotus
pulmonarius) terhadap hiperkolesterolemia. Tiga puluh enam tikus
Wistar-Kyoto dibahagikan kepada enam kumpulan, yang terdiri daripada normal
(N), hiperkolesterolemia (H), dua kumpulan untuk pencegahan (P1 dan P2) dan dua
kumpulan untuk rawatan (T1 dan T2). Untuk tujuan pencegahan, P1 dan P2 diaruh
menjadi hiperkolesterolemia dan pada masa yang sama diberi ekstrak
akues mentah P. pulmonarius (CA) atau
simvastatin selama 45 hari. Manakala tikus T1 dan T2 pula diberi makan secara
oral dengan CA atau simvastatin selama 30 hari lagi selepas 45 hari diaruh menjadi hiperkolesterolemia. Pada hari ke-45, kumpulan N, H, P1 dan P2 dikorbankan manakala
kumpulan T1 dan T2 dikorbankan pada hari ke-75. Pemeriksaan histopatologi
menunjukkan keadaan tisu hati. Titisan lemak diperhatikan pada tisu hepatik
hiperkolesterolemik dan juga tetap berada di dalam tisu hati tikus tergolong
dalam kelompok perawatan. Kelangsungan tisu lebih baik pada kumpulan pencegahan
yang menunjukkan bahawa sebatian yang terdapat di CA mungkin dapat melindungi
mereka daripada kerosakan selanjutnya. Analisis metabolik sera daripada tikus
P1 dan T1 mendedahkan perubahan beberapa metabolit seperti asid pantotenat,
N-karbamilglutamat, serotonin dan ceramida apabila dibandingkan dengan kumpulan
kawalan.
Kata kunci: Hiperkolesterolemia; histopatologi; metabolomik; sel hepatik
RUJUKAN
Alam, N., Yoon, K.N., Lee, J.S., Cho,
H.J., Shim, M.J. & Lee, T.S. 2011. Dietary effect of Pleurotus eryngiion biochemical function and
histology in hypercholesterolemic rats. Saudi Journal of Biological Sciences 18: 403-409.
Carrasco-Gonzalez, J.A.,
Serna-Saldivar, S.O. & Gutiérrez-Uribe, J.A. 2017. Nutritional composition
and nutraceutical properties of the Pleurotus fruiting bodies: Potential use as food ingredient. Journal of Food Composition
and Analysis 58: 69-81.
Dekker, M.J., Baker, C.,
Naples, M., Samsoondar, J., Zhang, R., Qiu, W., Sacco, J. & Adeli,
K. 2015. Inhibition of sphingolipid synthesis improves dyslipidemia in the diet-induced hamster model of insulin resistance: Evidence for the role
of spingosine and sphinganine in hepatic VLDL-apoB100 overproduction. Atherosclerosis 228: 98-109.
Feher, J. 2012. Pancreatic and biliary secretion. In Quantitative
Human Physiology: An Introduction, edited by Feher,
J. Elsevier, Amsterdam. pp. 721-730.
Figueras, J., Damingo,
E., Cortadellas, J., Padilla, F., Darado,
D.G., Segura, R., Galard, R. & Soler, J.S. 2005. Comparison of plasma serotonin level in
patients with variant angina pectoris versus healed myocardial infarction. The American Journal of Cardiology96:
204-207.
Gälman, C., Matasconi, M., Persson, L., Parini, P., Angelin, B. & Rudling, M. 2007. Age-induced hypercholesterolemia in the
rat relates to reduced elimination
but not increased intestinal absorption of cholesterol. The American Journal of Physiology -
Endocrinology and Metabolism 293: 737-742.
Grewal, A.S. 2014. Isatin derivatives with several biological activities. International Journal of Pharmaceutical Sciences and Research 6: 1-7.
Hara,
K., Hirowatari, Y., Yoshika, M., Kamiyama,
Y., Tsuka, Y. & Takahashi, H. 2004. The ratio of
plasma to whole-blood serotonin may be a novel marker of atherosclerotic
cardiovascular disease. Journal of Laboratory
and Clinical Medicine144: 31-37.
Harini, M. & Astirin, O. P.
2009. Blood cholesterol levels of hypercholesterolemic rat Rattus norvegicus) after VCO treatment. Nusantara
Bioscience 1(2): 53-58.
Makni, M., Fetoui, H., Gargouri, N.K., Garoui, E.M., Jaber, H., Makni, J., Boudawara, T. & Zeghal, N. 2008. Hypolipidemic and hepatoprotective effect of flax and pumpkin seed mixture
rich in omega-3 and omega-6 fatty acids in hypercholesterolemic rats. Food and Chemical Toxicology 46:
3714-3720.
Manoharan, S., Shuib, A.S., Abdullah, N., Ashrafzadeh,
A. & Kabir, N. 2018. Gly-Val-Arg, an
angiotensin-1-converting enzyme inhibitory tripeptide ameliorates hypertension
on spontaneously hypertensive rats. Process Biochemistry 69: 224-232.
McGarrah, R.W.,
Crown, S.B., Zhang, G-F., Shah, S.H. & Newgard, C.B. 2018. Cardiovascular metabolomics. Circular
Research 122: 1238-1258.
Mo, W., Wu, X., Jia, G., Zhao, H., Chen, X., Tang, J., Wu, C., Cai, J., Tian, G., Wang, J. & Liu, G. 2018. Role of dietary
supplementation with arganine or N-carbamylglutamate in modulating the inflammation,
antioxidant property, and mRNA expression of antioxidant-relative signalling
molecules in the spleen of rats under oxidative stress. Animal Nutrition 4: 322-328.
Nežic´, L., Amidžic´, L., Škrbic´, R., Gajanin, R., Nepovimova, E., Vališ, M., Kuča, K. & Jaćević,
V. 2019. Simvastatin inhibits endotoxin induced apoptosis in liver and spleen
through up-regulation of Survivin/NF-kB/p65
expression. Frontiers in Pharmacology 10: 1-13.
Rajput, M.S., Balekar,
N. & Jain, D.K. 2014. Lagenaria siceraria ameliorates atheromatous lesions by modulating HMG-CoA reductase and
lipoprotein lipase enzymes activity in hypercholesterolemic rats. Journal of Acute
Disease 2014: 14-21.
Ramírez, A.A., Jessica Lopez Peláez, J.L., Bermúdez, I.M.
& Botero, J.Y. 2020. Prevalence of hyperlipidemia and its associated factors in university
students in Colombia. Heliyon 6: e05417.
Silva, B.V. 2013. Isatin, a versatile molecule: Studies in Brazil. Journal of the Brazilian Chemical Society 24: 707-720.
Singh,
P., Zhang, Y., Sharma, P., Covassin, N., Soucek, F., Friedman, P.A. & Somers, V.K. 2018. Statins
decrease leptin expression in human white adipocytes. Physiological Reports 6(2): e13566.
Slaoui, M. & Fiette, L. 2011.
Chap 4: Histopathology procedures: From tissue to histopathological evaluation.
In Drug Safety Evaluation: Methods and Protocols, Methods in Molecular
Biology, Vol. 691, edited by Gautier, J.C. Springer Science+Business Media, LLC. pp. 69-82.
Souza,
R.D. & Chattree, A. 2015. Design, synthesis and
biological activities of Isatin derivatives. Chemical Science Transactions 4: 208-212.
Sugiura, T., Dohi,
Y., Yamashita, S., Hirowatari, Y., Fujii, S. & Ohte, N. 2016.
Serotonin in peripheral blood reflects oxidative stress and plays a crucial
role in atherosclerosis: Novel insights towards holistic anti-atherothrombotic strategy. Atherosclerosis 246: 157-160.
Thangiah, N., Su, T.T., Chinna,
K., Jalaludin, M.Y., Mohamed, M.N.A. & Abdul
Majid, H. 2021. Longitudinal assessment between lifestyle‑related risk
factors and a composite cardiovascular disease (CVD) risk index among
adolescents in Malaysia. Scientific Reports 11: 19135-19143.
Tousoulis, D., Antoniades,
C., Tentolouris, C., Goumas,
G., Stefanad, C. & Pavlos,
T. 2002. L-arganine in cardiovascular disease: Dream
or reality? Vascular Medicine 7: 203-211.
Wang, Q.,
Danxia Liu, D., Song, P.
& Zou, M-H. 2016. Deregulated
tryptophan-kynurenine pathway is linked to inflammation, oxidative stress, and
immune activation pathway in cardiovascular diseases. Frontiers in Bioscience 20: 1116-1142.
Warnholtz, A., Mollnou,
H., Oelze, M., Wendt, M. & Munzel,
T. 2001. Antioxidants and endothelial dysfunction in hyperclipidemia. Current Hypertension Report 3:
53-60.
Wirleitner, B., Neurauter, G., Schrocksnadel, K., Frick, B. & Fuchs, D. 2003.
Interferon-γ-Induced conversion of tryptophan: Immunologic and
neuropsychiatric aspects. Current Medicinal Chemistry 10: 1581-1591.
Wresdiyati, T., Hartanta,
A.B. & Astawan, M. 2008. The effect of seaweed Eucheuma cottonii on superoxide dismutase (SOD) liver of hypercholesterolemic rats. HAYATI Journal of Biosciences 15: 105-110.
Yang,
H., Hwang, I., Kim, S., Hong, E. & Jeung,
E. 2013. Lentinus edodes promotes fat removal in hypercholesterolemic mice. Experimental and Therapeutic Medicine 6:
1409-1413.
Zainal Abidin, M.H., Abdullah, N. & Zainal Abidin, N. 2016. Protective effect of antioxidant extracts
from grey oyster mushroom, Pleurotus pulmonarius (Agaricomycetes)
against human low-density lipoprotein oxidation and aortic endothelial cell
damage. International Journal of
Medicinal Mushrooms 18: 109-121.
*Pengarang untuk surat-menyurat; email: hanizaaminudin@um.edu.my