Sains Malaysiana 54(1)(2025): 255-263
http://doi.org/10.17576/jsm-2025-5401-20
Ameliorative
Effects of Betanin in Mice with Trimethyltin-Induced
Pancreatic and Hepatocytic Alterations
(Kesan Amelioratif Betanin pada Tikus dengan Perubahan Pankreas dan Hepatosit Terinduksi Trimethyltin)
Wachiryah Thong-asa*, Yanisa Detpakdee
& Kanlayawadee Srisoonthon
Animal Toxicology
and Physiology Specialty Research Unit (ATPSRU), Department of Zoology, Faculty
of Science, Kasetsart University, Bangkok 10900
Thailand
Received: 28 May
2024/Accepted: 4 November 2024
Abstract
The
effects of TMT on metabolic alteration are on the rise, including obesity and
diabetes. In the present study, we aimed to investigate the protective effect
of betanin (Bet) against TMT-induced glycemic disturbance and pancreatic and hepatocytic alterations, expanding on TMT’s and
Bet’s effects on metabolic diseases. Fifty male Institute of Cancer Research
(ICR) mice were randomly divided into Sham-veh,
TMT-L-veh, TMT-H-veh,
TMT-L-Bet100, and TMT-H-Bet100 groups. A low dose (L) (1 mg/kg) and high dose
(H) (2.6 mg/kg) of TMT were given via one-time intraperitoneal (i.p.) injection before intragastric gavage administration
of treatments for 4 consecutive weeks. A weekly oral glucose tolerance test
(OGTT) was conducted for glycemic control capacity
evaluation with serum insulin assessment. Pancreatic and hepatic tissues were
collected to analyze islet number and beta cell
density, glycogen content, and histopathology. TMT exposure did not
significantly change glycemic control capacity or
serum insulin level (p > 0.05). TMT significantly reduced pancreatic beta
cell density, and this was accompanied by a decrease in hepatic glycogen
content and an increase in hepatosteatosis and
inflammation (p < 0.05). Treatment with Bet significantly alleviated all
these alterations (p < 0.05). Bet showed alleviative effects against
TMT-induced pancreatic and hepatocytic alterations, including preventing
pancreatic beta cell damage, maintaining the liver’s glycogen content, anti-hepatosteatosis, and anti-inflammation.
Keywords:
Betanin; glycemic control; hepatosteatosis;
pancreatic beta cell; trimethyltin
Abstrak
Kesan TMT pada perubahan metabolik semakin meningkat, termasuk obesiti dan diabetes. Dalam kajian ini,
kami berhasrat untuk mengkaji kesan perlindungan betanin (Bet) terhadap gangguan glisemik aruhan-TMT dan perubahan pankreas dan hepatosit, mengembangkan kesan TMT dan Bet
pada penyakit metabolik.
Lima puluh tikus jantan Institut Penyelidikan Kanser (ICR) secara rawak dibahagikan kepada kumpulan Sham-veh, TMT-L-veh, TMT-H-veh, TMT-L-Bet100 dan TMT-H-Bet100. Dos rendah (L) (1 mg/kg) dan dos tinggi (H) (2.6 mg/kg) TMT diberikan melalui satu suntikan intraperitoneal (i.p.) sebelum diberikan rawatan gavage intragastrik selama 4 minggu berturut-turut. Ujian toleransi glukosa oral secara mingguan (OGTT) telah dijalankan untuk penilaian kapasiti kawalan glisemik dengan penilaian insulin serum. Tisu pankreas dan hati dikumpul untuk analisis nombor kelompok dan ketumpatan sel beta, kandungan glikogen dan histopatologi. Pendedahan TMT tidak banyak mengubah kapasiti kawalan glisemik atau aras insulin serum (p > 0.05). TMT mengurangkan ketumpatan sel beta pankreas dengan ketara dan menurunkan kandungan glikogen hepatik dan peningkatan dalam hepatosteatosis dan keradangan (p <0.05). Rawatan dengan Bet telah mengurangkan semua perubahan ini dengan ketara (p < 0.05). Bet menunjukkan kesan pengurangan terhadap perubahan pankreas dan hepatosit aruhan TMT, termasuk mencegah kerosakan sel beta pankreas, mengekalkan kandungan glikogen hati, anti-hepatosteatosis dan anti-keradangan.
Kata kunci: Betanin; kawalan glisemik; hepatosteatosis; sel beta pankreas; trimetiltin
REFERENCES
Aramsirirujiwet, Y., Leepasert,
T., Piamariya, D. & Thong-Asa, W. 2023. Benefits
of erinacines from different cultivate formulas on cognitive deficits and
anxiety-like behaviour in mice with trimethyltin-induced
toxicity. Tropical Life Science Research 34(3): 165-183.
Aschner, M. & Aschner,
J.L. 1992. Cellular and molecular effects of trimethyltin and triethyltin: Relevance to organotin
neurotoxicity. Neuroscience & Biobehavioral Reviews 16(4): 427-435.
Chen, L., Zhu, Y., Hu, Z., Wu, S. & Jin, C. 2021. Beetroot as a functional food with huge
health benefits: Antioxidant, antitumor, physical function, and chronic
metabolomics activity. Food Science & Nutrition 9(11): 6406-6420.
Choi, G.N., Kim, J.H., Kwak, J.H., Jeong, C-H., Jeong, H.R., Lee, U.
& Heo, H.J. 2012. Effect of quercetin on learning
and memory performance in ICR mice under neurotoxic trimethyltin exposure. Food Chemistry 132(2): 1019-1024.
Dhananjayan, I., Kathiroli,
S., Subramani, S. & Veerasamy, V. 2017.
Ameliorating effect of betanin, a natural chromoalkaloid by modulating hepatic carbohydrate metabolic enzyme activities and glycogen
content in streptozotocin - nicotinamide induced experimental rats. Biomedicine
& Pharmacotherapy 88: 1069-1079.
Ekuta, J.E., Hikal,
A.H. & Matthews, J.C. 1998. Toxicokinetics of trimethyltin in four inbred strains of mice. Toxicology
Letters 95(1): 41-46.
Esatbeyoglu, T., Wagner, A.E., Schini-Kerth,
V.B. & Rimbach, G. 2014. Betanin--a food colorant
with biological activity. Molecular Nutrition & Food Research 59(1):
36-47.
Geloso, M.C., Corvino, V. & Michetti, F. 2011. Trimethyltin-induced
hippocampal degeneration as a tool to investigate neurodegenerative processes. Neurochemistry
International 58(7): 729-738.
Han, J., Ma, D., Zhang, M., Yang, X. &
Tan, D. 2015. Natural antioxidant betanin protects rats from paraquat-induced
acute lung injury interstitial pneumonia. BioMed Research International 2015: 608174.
Kimbrough, R.D. 1976. Toxicity and health
effects of selected organotin compounds: A review. Environmental Health
Perspectives 14: 51-56.
Liu, Z., Tian, Z., Lv,
J., Liu, W., Ma, Y., Hu, M. & Huang, M. 2020. Mechanism in bradycardia
induced by Trimethyltin chloride: Inhibition activity
and expression of Na+/K+-ATPase and apoptosis in
myocardia. The Journal of Toxicological Sciences 45(9): 549-558.
Lugo-Radillo, A.,
Delgado-Enciso, I., Rodriguez-Hernandez, A.,
Peña-Beltran, E., Martinez-Martinez, R. & Galvan-Salazar, H. 2020.
Inhibitory effect of betanin from Hylocereus ocamponis against steatohepatitis in mice fed a
high-fat diet. Natural Product Communications 15(7): 1934578X20932013.
Martinez, R.M., Longhi-Balbinot,
D.T., Zarpelon, A.C., Staurengo-Ferrari,
L., Baracat, M.M., Georgetti,
S.R., Sassonia, R.C., Verri,
W.A. & Casagrande, R. 2015. Anti-inflammatory activity of betalain-rich dye of Beta vulgaris: Effect on edema, leukocyte recruitment, superoxide anion and cytokine
production. Archives of Pharmacal Research 38(4): 494-504.
Nagy, C. & Einwallner,
E. 2018. Study of in vivo glucose metabolism in high-fat diet-fed mice
using oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Journal
of Visualized Experiments 2018 (131): 56672.
Pagliarani, A., Nesci, S.
& Ventrella, V. 2013. Toxicity of organotin compounds: Shared and unshared
biochemical targets and mechanisms in animal cells. Toxicology in Vitro 27(2):
978-990.
Reddy, M.K., Alexander-Lindo, R.L. &
Nair, M.G. 2005. Relative inhibition of lipid peroxidation, cyclooxygenase
enzymes, and human tumor cell proliferation by natural
food colors. Journal of Agricultural and Food
Chemistry 53(23): 9268-9273.
Regufe, V.M.G., Pinto, C. & Perez, P. 2020.
Metabolic syndrome in type 2 diabetic patients: A review of current evidence. Porto
Biomedical Journal 5(6): e101.
Sharma, S.N., Nayak, S., Pradhan, S.P.,
Nayak, S., Nayak, P. & Patnaik, L. 2023. Effect of anti-fouling organotin
compound (TBTCl) and the ameliorative role of
spirulina on Lamellidens marginalis. Environmental Quality Management 33(4):
285-294.
Shoaib, S., Ansari, M.A., Fatease, A.A., Safhi, A.Y., Hani,
U., Jahan, R., Alomary, M.N., Ansari, M.N., Ahmed,
N., Wahab, S., Ahmad, W., Yusuf, N. & Islam, N. 2023. Plant-derived
bioactive compounds in the management of neurodegenerative disorders:
Challenges, future directions and molecular mechanisms involved in
neuroprotection. Pharmaceutics 15(3): 749.
Silva, D., Baião,
D.D.S., Ferreira, V.F. & Paschoalin, V.M.F. 2022.
Betanin as a multipath oxidative stress and inflammation modulator: A beetroot
pigment with protective effects on cardiovascular disease pathogenesis. Critical
Reviews in Food Science and Nutrition 62(2): 539-554.
Thong-Asa, W., Jedsadavitayakol,
S. & Jutarattananon, S. 2021. Benefits of betanin
in rotenone-induced Parkinson mice. Metabolic Brain Disease 36(8):
2567-2577.
Thong-Asa, W., Prasartsri,
S., Klomkleaw, N. & Thongwan,
N. 2020. The neuroprotective effect of betanin in trimethyltin-induced
neurodegeneration in mice. Metabolic Brain Disease 35(8): 1395-1405.
Thong-asa, W., Prasertsuksri, P., Sakamula, R. & Nimnuan, T.J.S.M. 2019. Effect of Tiliacora triandra leaf extract on glycemic control in mice with high sugar intake. Sains Malaysiana 48(9): 1989-1995.
Tinkov, A.A., Ajsuvakova,
O.P., Skalnaya, M.G., Skalny,
A.V., Aschner, M., Suliburska,
J. & Aaseth, J. 2019. Organotins in obesity and associated metabolic disturbances. Journal of Inorganic
Biochemistry 191: 49-59.
Trovato, F., Catalano, D., Musumeci,
G. & Trovato, G. 2014. 4Ps medicine of the fatty
liver: The research model of predictive, preventive, personalized and
participatory medicine-recommendations for facing obesity, fatty liver and
fibrosis epidemics. EPMA Journal 5(1): 21.
Wang, Y., Liu, X., Jing, H., Ren, H., Xu,
S. & Guo, M. 2022. Trimethyltin induces apoptosis
and necroptosis of mouse liver by oxidative stress through YAP phosphorylation. Ecotoxicology and Environmental Safety 248: 114327.
Yau, B., Madsen, S., Nelson, M.E., Cooke,
K.C., Fritzen, A.M., Thorius, I.H., Stöckli, J., James, D.E. & Kebede, M.A. 2024. Genetics
and diet shape the relationship between islet function and whole
body metabolism. American Journal of Physiology-Endocrinology and
Metabolism 326(5): 663-672.
Ye, M., Han, B.H., Kim, J.S., Kim, K. &
Shim, I. 2020. Neuroprotective effect of bean phosphatidylserine on TMT-induced
memory deficits in a rat model. International Journal of Molecular Sciences 21(14):
4901.
Zhang, Y., Cui, J., Li, K., Xu, S., Yin,
H., Li, S. & Gao, X.J. 2023. Trimethyltin chloride exposure induces apoptosis and necrosis and impairs islet function
through autophagic interference. Ecotoxicology and Environmental Safety 267: 115628.
Zuo, Z., Chen, S., Wu, T., Zhang, J., Su, Y., Chen, Y. & Wang, C. 2011. Tributyltin causes
obesity and hepatic steatosis in male mice. Environmental Toxicology 26(1):
79-85.
*Corresponding author; email:
fsciwyth@ku.ac.th