Ameliorative Effects of Orlistat and Metformin Either Alone or in Combination on Liver Functions, Structure, Immunoreactivity and Antioxidant Enzymes in Experimentally Induced Obesity in Male Rats

Overview

Journal Heliyon

Specialty Social Sciences

Date 2023 Aug 21

PMID 37600390

Authors

Reham Z Hamza

Khadeejah Alsolami

Affiliations

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Abstract

Background: Prevalence of obesity is increasing worldwide. Obesity is associated with incidences of metabolic disorders and cardiovascular diseases and the risk of having it rose sharply during the COVID-19 pandemic. Obesity is associated with oxidative stress, inflammatory markers and hepatic disorders and has become one of the silent killer diseases affecting global health.

Methods: This study examined the effects of obesity on liver functions (ALT, AST and LDH), lipid profile (TG, TC, HDL-c, LDL-c and vLDL-c), tumour necrosis factor alpha (TNF-α), inflammatory marker, C-reactive protein (CRP), leptin hormone and antioxidant enzymes (CAT, SOD and GPx) and lipid peroxidation marker (MDA) in liver homogenates besides histological structure of the liver tissues and assessment of DNA damage. Fifty male Wistar rats were used and they were divided into five treatment groups: I-Control group, II-high-fat diet (HFD) treated group (Obesity) group, III-HFD plus Orlistat (ORL), IV-HFD plus metformin (Met) and V- HFD plus ORL plus Met.

Results: Experimentally-induced obesity caused a significant increase in liver enzymes including lipid markers (triglycerides and total cholesterol), inflammatory markers, tumour markers and lipid peroxidation markers and a concurrent decline in antioxidant enzymes and damage of liver main structures characterised by presence of congestion and accumulation of mononuclear inflammatory cells in blood sinusoids. In contrast, groups treated with either ORL or Met or both group, we recorded restoration of normal hepatic structures and a decline in DNA damage, liver enzymes and antioxidant levels. The best restoration and amelioration were observed in the group treated with a combination of ORL and Met.

Conclusion: Our findings indicated the synergistic effect of ORL and Met in ameliorating hepatic functions and lipid profile, alleviating inflammation, genotoxicity and side effects of experimentally-induced obesity.

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References

Othman Z, Zakaria Z, Suleiman J, Ghazali W, Mohamed M . Anti-Atherogenic Effects of Orlistat on Obesity-Induced Vascular Oxidative Stress Rat Model. Antioxidants (Basel). 2021; 10(2). PMC: 7915029. DOI: 10.3390/antiox10020251. View

Suleiman J, Nna V, Zakaria Z, Othman Z, Abu Bakar A, Mohamed M . Obesity-induced testicular oxidative stress, inflammation and apoptosis: Protective and therapeutic effects of orlistat. Reprod Toxicol. 2020; 95:113-122. DOI: 10.1016/j.reprotox.2020.05.009. View

Yang X, Xu Z, Zhang C, Cai Z, Zhang J . Metformin, beyond an insulin sensitizer, targeting heart and pancreatic β cells. Biochim Biophys Acta Mol Basis Dis. 2016; 1863(8):1984-1990. DOI: 10.1016/j.bbadis.2016.09.019. View

Foretz M, Guigas B, Viollet B . Metformin: update on mechanisms of action and repurposing potential. Nat Rev Endocrinol. 2023; 19(8):460-476. PMC: 10153049. DOI: 10.1038/s41574-023-00833-4. View

Kim E, Lee S, Jhun J, Byun J, Jeong J, Lee S . Metformin Prevents Fatty Liver and Improves Balance of White/Brown Adipose in an Obesity Mouse Model by Inducing FGF21. Mediators Inflamm. 2016; 2016:5813030. PMC: 4745345. DOI: 10.1155/2016/5813030. View

Lee A, Morley J . Metformin decreases food consumption and induces weight loss in subjects with obesity with type II non-insulin-dependent diabetes. Obes Res. 1998; 6(1):47-53. DOI: 10.1002/j.1550-8528.1998.tb00314.x. View

Lopaschuk G, Folmes C, Stanley W . Cardiac energy metabolism in obesity. Circ Res. 2007; 101(4):335-47. DOI: 10.1161/CIRCRESAHA.107.150417. View

Kang J, Kang J . Lifestyle measures in the management of gastro-oesophageal reflux disease: clinical and pathophysiological considerations. Ther Adv Chronic Dis. 2015; 6(2):51-64. PMC: 4331235. DOI: 10.1177/2040622315569501. View

Endoh D, Okui T, Ozawa S, Yamato O, Kon Y, Arikawa J . Protective effect of a lignan-containing flaxseed extract against CCl(4)-induced hepatic injury. J Vet Med Sci. 2002; 64(9):761-5. DOI: 10.1292/jvms.64.761. View

10.

Hurren K, Dunham M . Understanding the impact of commonly utilized, non-insulin, glucose-lowering drugs on body weight in patients with type 2 diabetes. Expert Opin Pharmacother. 2018; 19(10):1087-1095. DOI: 10.1080/14656566.2018.1494727. View

11.

Meuwese M, de Groot E, Duivenvoorden R, Trip M, Ose L, Maritz F . ACAT inhibition and progression of carotid atherosclerosis in patients with familial hypercholesterolemia: the CAPTIVATE randomized trial. JAMA. 2009; 301(11):1131-9. DOI: 10.1001/jama.301.11.1131. View

12.

Simonen P, Gylling H, Miettinen T . Body weight modulates cholesterol metabolism in non-insulin dependent type 2 diabetics. Obes Res. 2002; 10(5):328-35. DOI: 10.1038/oby.2002.46. View

13.

DeCensi A, Puntoni M, Goodwin P, Cazzaniga M, Gennari A, Bonanni B . Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prev Res (Phila). 2010; 3(11):1451-61. DOI: 10.1158/1940-6207.CAPR-10-0157. View

14.

Pemberton A, Brown J . In vitro interactions of extracellular histones with LDL suggest a potential pro-atherogenic role. PLoS One. 2010; 5(3):e9884. PMC: 2845606. DOI: 10.1371/journal.pone.0009884. View

15.

Chen K, Li Y, Guo Z, Zeng Y, Zhang W, Wang H . Metformin: current clinical applications in nondiabetic patients with cancer. Aging (Albany NY). 2020; 12(4):3993-4009. PMC: 7066888. DOI: 10.18632/aging.102787. View

16.

Aldekhail N, Logue J, McLoone P, Morrison D . Effect of orlistat on glycaemic control in overweight and obese patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Obes Rev. 2015; 16(12):1071-80. DOI: 10.1111/obr.12318. View

17.

Swinburn B, Carey D, Hills A, Hooper M, Marks S, Proietto J . Effect of orlistat on cardiovascular disease risk in obese adults. Diabetes Obes Metab. 2005; 7(3):254-62. DOI: 10.1111/j.1463-1326.2004.00467.x. View

18.

Gordon T, Kannel W . Obesity and cardiovascular diseases: the Framingham study. Clin Endocrinol Metab. 1976; 5(2):367-75. DOI: 10.1016/s0300-595x(76)80026-6. View

19.

Karise I, Bargut T, Del Sol M, Aguila M, Mandarim-de-Lacerda C . Metformin enhances mitochondrial biogenesis and thermogenesis in brown adipocytes of mice. Biomed Pharmacother. 2019; 111:1156-1165. DOI: 10.1016/j.biopha.2019.01.021. View

20.

Bovet P, Chiolero A, Gedeon J . Health Effects of Overweight and Obesity in 195 Countries. N Engl J Med. 2017; 377(15):1495-6. DOI: 10.1056/NEJMc1710026. View