The effects of pioglitazone and rosiglitazone on liver function in hypothyroid rats
-
Yousef Baghcheghi
,
Hedyeh Askarpour
Abstract
Objectives
This study aimed to investigate the antioxidant effect of rosiglitazone (ROG) and pioglitazone (POG) on oxidative damage and dysfunction of hepatic tissue in hypothyroid rats.
Methods
The male rats were classified into six groups: (1) Control; (2) Hypothyroid, (3) Hypothyroid-POG 10, (4) Hypothyroid-POG 20, (5) Hypothyroid-ROG 2, and (6) Hypothyroid-ROG 4. To induction hypothyroidism in rats, propylthiouracil (PTU) (0.05 %w/v) was added to drinking water. In groups 2–6, besides PTU, the rats were also intraperitoneal administrated with 10 or 20 mg/kg POG or 2 or 4 mg/kg ROG for six weeks. Finally, after deep anesthesia, the blood was collected to measure the serum biochemical markers and hepatic tissue was separated for biochemical oxidative stress markers.
Results
Administration of PTU significantly reduced serum thyroxin concentration, total thiol levels, activity of superoxide dismutase (SOD) and catalase (CAT) enzymes, and increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (Alk-P) and malondialdehyde (MDA) in the liver. Additionally, our results showed that prescription of POG or ROG for six weeks to hypothyroid rats resulted in an improvement in liver dysfunction (decrease in serum levels of AST, ALT, and ALK-P) through reducing oxidative damage in hepatic tissue (increase in CAT, SOD, or total thiols and decrease in MDA levels).
Conclusions
The findings of the present study presented that the IP administration of POG and ROG for six weeks improves liver dysfunction induced by hypothyroidism in juvenile rats by reducing oxidative damage.
Funding source: Mashhad University of Medical Sciences, Mashhad, Iran
Award Identifier / Grant number: 990502
Acknowledgments
This work was supported by the Research Council of Mashhad University of Medical Sciences (NO: 990502).
-
Research ethics: Ethical code: IR.MUMS.MEDICAL.REC.1399.304.
-
Informed consent: Informed consent was obtained from all individuals included in this study.
-
Author contributions: All authors (Yousef Baghcheghi, Farimah Beheshti, Fatemeh Seyedi, Mahdiyeh Hedayati-Moghadam, Hedyeh Askarpour, Aliasghar Kheirkhah, Ahmad Golkar, Mohammad Dalfardi, Mahmoud Hosseini) have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Competing interests: Authors state no conflict of interest.
-
Research funding: This study was financially supported by Research Council of Mashhad University of Medical Sciences, Mashhad, Iran (NO: 990502).
References
1. Li, S, Tan, H-Y, Wang, N, Zhang, Z-J, Lao, L, Wong, C-W, et al.. The role of oxidative stress and antioxidants in liver diseases. Int J Mol Sci 2015;16:26087–124.10.3390/ijms161125942Search in Google Scholar PubMed PubMed Central
2. Yaribeygi, H, Faghihi, N, Mohammadi, MT, Sahebkar, A. Effects of atorvastatin on myocardial oxidative and nitrosative stress in diabetic rats. Comp Clin Pathol 2018;27:691–7.10.1007/s00580-018-2652-2Search in Google Scholar
3. Mullur, R, Liu, Y-Y, Brent, GA. Thyroid hormone regulation of metabolism. Physiol Rev 2014;94:355–82.10.1152/physrev.00030.2013Search in Google Scholar PubMed PubMed Central
4. Visser, T. Pathways of thyroid hormone metabolism. Acta Med Austriaca 1996;23:10–6.Search in Google Scholar
5. Lushchak, VI. Free radicals, reactive oxygen species, oxidative stress and its classification. Chem Biol Interact 2014;224:164–75.10.1016/j.cbi.2014.10.016Search in Google Scholar PubMed
6. Baghcheghi, Y, Salmani, H, Beheshti, F, Shafei, MN, Sadeghnia, HR, Soukhtanloo, M, et al.. Effects of PPAR-γ agonist, pioglitazone on brain tissues oxidative damage and learning and memory impairment in juvenile hypothyroid rats. Int J Neurosci 2019;129:1024–38.10.1080/00207454.2019.1632843Search in Google Scholar PubMed
7. Cano-Europa, E, Blas-Valdivia, V, Lopez-Galindo, GE, Franco-Colin, M, Pineda-Reynoso, M, Hernandez-Garcia, A, et al.. Methimazole-induced hypothyroidism causes alteration of the REDOX environment, oxidative stress, and hepatic damage; events not caused by hypothyroidism itself. Ann Hepatol 2010;9:80–8.10.1016/S1665-2681(19)31684-9Search in Google Scholar
8. Baghcheghi, Y, Beheshti, F, Hosseini, M, Gowhari-Shabgah, A, Ali-Hassanzadeh, M, Hedayati-Moghadam, M. Cardiovascular protective effects of PPARγ agonists in hypothyroid rats: protection against oxidative stress. Clin Exp Hypertens 2022;44:539–47.10.1080/10641963.2022.2079669Search in Google Scholar PubMed
9. Murphy, GJ, Holder, JC. PPAR-γ agonists: therapeutic role in diabetes, inflammation and cancer. Trends Pharmacol Sci 2000;21:469–74.10.1016/S0165-6147(00)01559-5Search in Google Scholar PubMed
10. Chan, SH, Wu, KL, Kung, PS, Chan, JY. Oral intake of rosiglitazone promotes a central antihypertensive effect via upregulation of peroxisome proliferator-activated receptor-γ and alleviation of oxidative stress in rostral ventrolateral medulla of spontaneously hypertensive rats. Hypertension 2010;55:1444–53.10.1161/HYPERTENSIONAHA.109.149146Search in Google Scholar PubMed
11. Hunter, RL, Bing, G. Agonism of peroxisome proliferator receptor-gamma may have therapeutic potential for neuroinflammation and Parkinson’s disease. Curr Neuropharmacol 2007;5:35–46.10.2174/157015907780077123Search in Google Scholar PubMed PubMed Central
12. Gupte, AA, Liu, JZ, Ren, Y, Minze, LJ, Wiles, JR, Collins, AR, et al.. Rosiglitazone attenuates age‐and diet‐associated nonalcoholic steatohepatitis in male low‐density lipoprotein receptor knockout mice. Hepatology 2010;52:2001–11.10.1002/hep.23941Search in Google Scholar PubMed PubMed Central
13. Rani, N, Bharti, S, Bhatia, J, Nag, T, Ray, R, Arya, DS. Chrysin, a PPAR-γ agonist improves myocardial injury in diabetic rats through inhibiting AGE-RAGE mediated oxidative stress and inflammation. Chem Biol Interact 2016;250:59–67.10.1016/j.cbi.2016.03.015Search in Google Scholar PubMed
14. Wu, L, Guo, C, Wu, J. Therapeutic potential of PPARγ natural agonists in liver diseases. J Cell Mol Med 2020;24:2736–48.10.1111/jcmm.15028Search in Google Scholar PubMed PubMed Central
15. Baghcheghi, Y, Beheshti, F, Salmani, H, Soukhtanloo, M, Hosseini, M. Protective effect of PPARγ agonists on cerebellar tissues oxidative damage in hypothyroid rats. Neurol Res Int 2016;2016:1–9.10.1155/2016/1952561Search in Google Scholar PubMed PubMed Central
16. Yaribeygi, H, Mohammadi, MT, Butler, AE, Sahebkar, A. PPAR-α agonist fenofibrate potentiates antioxidative elements and improves oxidative stress of hepatic cells in streptozotocin-induced diabetic animals. Comp Clin Pathol 2019;28:203–9.10.1007/s00580-018-2816-0Search in Google Scholar
17. Pourganji, M, Hosseini, M, Soukhtanloo, M, Zabihi, H, Hadjzadeh, MA-r. Protective role of endogenous ovarian hormones against learning and memory impairments and brain tissues oxidative damage induced by lipopolysaccharide. Iran Red Crescent Med J 2014;16:e13954.10.5812/ircmj.13954Search in Google Scholar PubMed PubMed Central
18. Beheshti, F, Akbari, HR, Baghcheghi, Y, Mansouritorghabeh, F, Mortazavi Sani, SS, Hosseini, M, et al.. Beneficial effects of angiotensin converting enzyme inhibition on scopolamine-induced learning and memory impairment in rats, the roles of brain-derived neurotrophic factor, nitric oxide and neuroinflammation. Clin Exp Hypertens 2021;43:505–515.10.1080/10641963.2021.1901112Search in Google Scholar PubMed
19. Anaeigoudari, A, Shafei, MN, Soukhtanloo, M, Sadeghnia, HR, Reisi, P, Beheshti, F, et al.. Lipopolysaccharide-induced memory impairment in rats is preventable using 7-nitroindazole. Arq Neuropsiquiatr 2015;73:784–90.10.1590/0004-282X20150121Search in Google Scholar PubMed
20. Anaeigoudari, A, Soukhtanloo, M, Shafei, MN, Sadeghnia, HR, Reisi, P, Beheshti, F, et al.. Neuronal nitric oxide synthase has a role in the detrimental effects of lipopolysaccharide on spatial memory and synaptic plasticity in rats. Pharmacol Rep 2016;68:243–9.10.1016/j.pharep.2015.09.004Search in Google Scholar PubMed
21. Hedayati, M, Niazmand, S, Hosseini, M, Baghcheghi, Y, Beheshti, F, Niazmand, M, et al.. Vitamin E improved redox homeostasis in heart and aorta of hypothyroid rats. Endocr Regul 2018;51:205–12.10.1515/enr-2017-0021Search in Google Scholar PubMed
22. Baghcheghi, Y, Mansouri, S, Beheshti, F, Shafei, MN, Salmani, H, Reisi, P, et al.. Neuroprotective and long-term potentiation improving effects of vitamin E in juvenile hypothyroid rats. Int J Vitam Nutr Res 2019;90:1–13.10.1024/0300-9831/a000533Search in Google Scholar PubMed
23. Baghcheghi, Y, Beheshti, F, Salmani, H, Hosseini, M. Brain‑derived neurotrophic factor and nitric oxide contribute to protective effects of rosiglitazone on learning and memory in hypothyroid rats. Acta Neurobiol Exp 2021;81:218–32.10.21307/ane-2021-021Search in Google Scholar PubMed
24. Salama, AF, Tousson, E, Ibrahim, W, Hussein, WM. Biochemical and histopathological studies of the PTU-induced hypothyroid rat kidney with reference to the ameliorating role of folic acid. Toxicol Ind Health 2013;29:600–8.10.1177/0748233711432577Search in Google Scholar PubMed
25. Hosseini, M, Ghasemi, S, Hadjzadeh, MAR, Ghorbani, A, Aghili, S, Aghaei, A, et al.. Administration of Nigella sativa during neonatal and juvenile growth period improved liver function of propylthiouracil-induced hypothyroid rats. J Matern Fetal Neonatal Med 2020;33:718–25.10.1080/14767058.2018.1500540Search in Google Scholar PubMed
26. Esmaeilizadeh, M, Hosseini, M, Beheshti, F, Alikhani, V, Keshavarzi, Z, Shoja, M, et al.. Vitamin C improves liver and renal functions in hypothyroid rats by reducing tissue oxidative injury. Int J Vitam Nutr Res 2020;90:84–94.10.1024/0300-9831/a000495Search in Google Scholar PubMed
27. Ajala, M, Ogunro, P, Fasanmade, O. Relationship between liver function tests and thyroid hormones in thyroid disorders. Niger Postgrad Med J 2013;20:188–92.10.4103/1117-1936.164708Search in Google Scholar
28. Bayraktar, M, Van Thiel, D. Abnormalities in measures of liver function and injury in thyroid disorders. Hepato Gastroenterology 1997;44:1614–8.Search in Google Scholar
29. Chattopadhyay, S, Sahoo, D, Subudhi, U, Chainy, G. Differential expression profiles of antioxidant enzymes and glutathione redox status in hyperthyroid rats: a temporal analysis. Comp Biochem Physiol C Toxicol Pharmacol 2007;146:383–91.10.1016/j.cbpc.2007.04.010Search in Google Scholar PubMed
30. Ngaha, E, Akanji, M, Madusolumuo, M. Studies on correlations between chloroquine-induced tissue damage and serum enzyme changes in the rat. Experientia 1989;45:143–6.10.1007/BF01954851Search in Google Scholar PubMed
31. Tanase, DM, Gosav, EM. Hypothyroidism-induced nonalcoholic fatty liver disease (HIN): mechanisms and emerging therapeutic options. Int J Mol Med Sci 2020;21:5927.10.3390/ijms21165927Search in Google Scholar PubMed PubMed Central
32. Yilmaz, S, Ozan, S, Benzer, F, Canatan, H. Oxidative damage and antioxidant enzyme activities in experimental hypothyroidism. Cell Biochem Funct 2003;21:325–30.10.1002/cbf.1031Search in Google Scholar PubMed
33. Subudhi, U, Chainy, GB. Curcumin and vitamin E modulate hepatic antioxidant gene expression in PTU-induced hypothyroid rats. Mol Biol Rep 2012;39:9849–61.10.1007/s11033-012-1851-1Search in Google Scholar PubMed
34. Zhao, P, Hu, Z, Ma, W, Zang, L, Tian, Z, Hou, Q. Quercetin alleviates hyperthyroidism-induced liver damage via Nrf2 Signaling pathway. Biofactors 2020;46:608–19.10.1002/biof.1626Search in Google Scholar PubMed
35. Kharazmkia, A, Ziaie, S, Ahmadpoor, P, Moradi, O, Khoshdel, A, Pour-Reza-Gholi, F, et al.. A triple-blind randomized controlled trial on impacts of pioglitazone on oxidative stress markers in diabetic kidney transplant recipients. Shiraz E-Med J 2020;21:e98656.10.5812/semj.98656Search in Google Scholar
36. Gumieniczek, A. Effect of the new thiazolidinedione-pioglitazone on the development of oxidative stress in liver and kidney of diabetic rabbits. Life Sci 2003;74:553–62.10.1016/j.lfs.2003.03.004Search in Google Scholar PubMed
37. Razavizade, M, Jamali, R, Arj, A, Matini, SM, Moraveji, A, Taherkhani, E. The effect of pioglitazone and metformin on liver function tests, insulin resistance, and liver fat content in nonalcoholic Fatty liver disease: a randomized double blinded clinical trial. Hepat Mon 2013;13.10.5812/hepatmon.9270Search in Google Scholar PubMed PubMed Central
38. Von Bibra, H, Diamant, M, Scheffer, PG, Siegmund, T, Schumm-Draeger, P-M. Rosiglitazone, but not glimepiride, improves myocardial diastolic function in association with reduction in oxidative stress in type 2 diabetic patients without overt heart disease. Diabetes Vasc Dis Res 2008;5:310–8.10.3132/dvdr.2008.045Search in Google Scholar PubMed
39. Yang, H-Y, Lin, H-S, Chao, JC, Chien, Y-W, Peng, H-C, Chen, J-R. Effects of soy protein on alcoholic liver disease in rats undergoing ethanol withdrawal. J Nutr Biochem 2012;23:679–84.10.1016/j.jnutbio.2011.03.016Search in Google Scholar PubMed
40. Shokrzadeh, M, Shobi, S, Attar, H, Shayegan, S, Payam, S, Ghorbani, F. Effect of vitamins A, E and C on liver enzyme activity in rats exposed to organophosphate pesticide diazinon. Pakistan J Biol Sci 2012;15:936–41.10.3923/pjbs.2012.936.941Search in Google Scholar PubMed
41. Linares, I, Farrokhi, K, Echeverri, J, Kaths, JM, Kollmann, D, Hamar, M, et al.. PPAR-gamma activation is associated with reduced liver ischemia-reperfusion injury and altered tissue-resident macrophages polarization in a mouse model. PLoS One 2018;13:e0195212.10.1371/journal.pone.0195212Search in Google Scholar PubMed PubMed Central
42. Ferguson, HE, Thatcher, TH, Olsen, KC, Garcia-Bates, TM, Baglole, CJ, Kottmann, R, et al.. Peroxisome proliferator-activated receptor-γ ligands induce heme oxygenase-1 in lung fibroblasts by a PPARγ-independent, glutathione-dependent mechanism. Am J Physiol Lung Cell Mol Physiol 2009;297:L912–9.10.1152/ajplung.00148.2009Search in Google Scholar PubMed PubMed Central
43. Galli, A, Ceni, E, Crabb, D, Mello, T, Salzano, R, Grappone, C, et al.. Antidiabetic thiazolidinediones inhibit invasiveness of pancreatic cancer cells via PPARγ independent mechanisms. Gut 2004;53:1688–97.10.1136/gut.2003.031997Search in Google Scholar PubMed PubMed Central
44. Galli, A, Ceni, E, Mello, T, Polvani, S, Tarocchi, M, Buccoliero, F, et al.. Thiazolidinediones inhibit hepatocarcinogenesis in hepatitis B virus–transgenic mice by peroxisome proliferator‐activated receptor γ–independent regulation of nucleophosmin. Hepatology 2010;52:493–505.10.1002/hep.23669Search in Google Scholar PubMed
45. Kapadia, R, Yi, J-H, Vemuganti, R. Mechanisms of anti-inflammatory and neuroprotective actions of PPAR-gamma agonists. Front Biosci 2008;13:1813.10.2741/2802Search in Google Scholar PubMed PubMed Central
46. Wang, X, Wang, Z, Liu, JZ, Hu, JX, Chen, HL, Li, WL, et al.. Double antioxidant activities of rosiglitazone against high glucose-induced oxidative stress in hepatocyte. Toxicol Vitro 2011;25:839–47.10.1016/j.tiv.2011.02.004Search in Google Scholar PubMed
47. Tepmongkol, S, Keelawat, S, Honsawek, S, Ruangvejvorachai, P. Rosiglitazone effect on radioiodine uptake in thyroid carcinoma patients with high thyroglobulin but negative total body scan: a correlation with the expression of peroxisome proliferator–activated receptor-gamma. Thyroid 2008;18:697–704.10.1089/thy.2008.0056Search in Google Scholar PubMed
© 2024 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Reviews
- Markhamia lutea leaves aqueous and ethanolic extract with curative anti-inflammatory activity attenuates paclitaxel toxicity in rat’s intestine
- Does hydrotherapy influence plasma glucose levels in type 2 diabetes? – A scoping review
- Comparative effectiveness is the common denominator in health services research: experimental effects are promising, real-world effects are compelling
- Research Articles
- Hydroethanolic extract of Piliostigma thonningii leaves extenuates the severity of diarrhoea in female Wistar rats
- Pharmacokinetic assessment of rifampicin and des-acetyl rifampicin in carbon tetrachloride induced liver injury model in Wistar rats
- Antipyretic activity of the hydro-alcoholic extract of Artemisia absinthium L. as a standalone and as an adjuvant with barley water against yeast-induced pyrexia in albino Wistar rats
- Selenium prevented renal tissue damage in lipopolysaccharide-treated rats
- Preliminary data on cytotoxicity and functional group assessment of a herb–mineral combination against colorectal carcinoma cell line
- Oral intake of collagen hydrolysate from mackerel scad (Decapterus macarellus) attenuates skin photoaging by suppressing the UVB-induced expression of MMP-1 and IL-6
- Pentaclethra macrophylla leaves reduce blood glucose level, improve sexual behavior and modulate critical enzymes associated with diabetes-erectile dysfunction morbidity in rats
- Anti-melanoma and antioxidant properties of the methanol extract from the leaves of Phragmenthera capitata (Spreng.) Balle and Globimetula braunii (Engl.) Van Tiegh
- The assessment of the mechanism of action of lauric acid in the context of oral cancer through integrative approach combining network pharmacology and molecular docking technology
- Therapeutic potential of flavonoids in ovalbumin induced asthma in mice model
- The effects of pioglitazone and rosiglitazone on liver function in hypothyroid rats
- Effect of ozone gas on viral kinetics and liver histopathology in hepatitis C patients
Articles in the same Issue
- Frontmatter
- Reviews
- Markhamia lutea leaves aqueous and ethanolic extract with curative anti-inflammatory activity attenuates paclitaxel toxicity in rat’s intestine
- Does hydrotherapy influence plasma glucose levels in type 2 diabetes? – A scoping review
- Comparative effectiveness is the common denominator in health services research: experimental effects are promising, real-world effects are compelling
- Research Articles
- Hydroethanolic extract of Piliostigma thonningii leaves extenuates the severity of diarrhoea in female Wistar rats
- Pharmacokinetic assessment of rifampicin and des-acetyl rifampicin in carbon tetrachloride induced liver injury model in Wistar rats
- Antipyretic activity of the hydro-alcoholic extract of Artemisia absinthium L. as a standalone and as an adjuvant with barley water against yeast-induced pyrexia in albino Wistar rats
- Selenium prevented renal tissue damage in lipopolysaccharide-treated rats
- Preliminary data on cytotoxicity and functional group assessment of a herb–mineral combination against colorectal carcinoma cell line
- Oral intake of collagen hydrolysate from mackerel scad (Decapterus macarellus) attenuates skin photoaging by suppressing the UVB-induced expression of MMP-1 and IL-6
- Pentaclethra macrophylla leaves reduce blood glucose level, improve sexual behavior and modulate critical enzymes associated with diabetes-erectile dysfunction morbidity in rats
- Anti-melanoma and antioxidant properties of the methanol extract from the leaves of Phragmenthera capitata (Spreng.) Balle and Globimetula braunii (Engl.) Van Tiegh
- The assessment of the mechanism of action of lauric acid in the context of oral cancer through integrative approach combining network pharmacology and molecular docking technology
- Therapeutic potential of flavonoids in ovalbumin induced asthma in mice model
- The effects of pioglitazone and rosiglitazone on liver function in hypothyroid rats
- Effect of ozone gas on viral kinetics and liver histopathology in hepatitis C patients
