Reduced Cytokine Tumour Necrosis Factor by Pharmacological Intervention in a Preclinical Study

Armin Mooranian; Jacqueline Chester; Edan Johnston; Corina Mihaela Ionescu; Daniel Walker; Melissa Jones; Susbin Raj Wagle; Bozica Kovacevic; Thomas Foster; Momir Mikov; Hani Al-Salami

doi:10.3390/biom12070877

Reduced Cytokine Tumour Necrosis Factor by Pharmacological Intervention in a Preclinical Study

Biomolecules. 2022 Jun 23;12(7):877. doi: 10.3390/biom12070877.

Authors

Armin Mooranian^{1

2}, Jacqueline Chester^{1

2}, Edan Johnston^{1

2}, Corina Mihaela Ionescu^{1

2}, Daniel Walker^{1

2}, Melissa Jones^{1

2}, Susbin Raj Wagle^{1

2}, Bozica Kovacevic^{1

2}, Thomas Foster^{1

2}, Momir Mikov³, Hani Al-Salami^{1

2}

Affiliations

¹ The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia.
² Hearing Therapeutics Department, Ear Science Institute Australia, Queen Elizabeth II Medical Centre, Nedlands, Perth, WA 6009, Australia.
³ Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21101 Novi Sad, Serbia.

Abstract

Recent preclinical studies in our laboratory have shown that the bile acid profile is altered during diabetes development and such alteration has been linked to the diabetes-associated inflammatory profile. Hence, this study aimed to investigate if the first-line antidiabetic drug metformin will alter the bile acid profile and diabetes-associated inflammation in a murine model of pre-type 2 diabetes. C57 mice were randomly allocated into three equal groups of eight. Group One was given a low-fat diet (LFD), Group Two was given a high-fat diet (HFD), and Group Three was given an HFD and, upon prediabetes confirmation, daily oral metformin for one month. Blood glucose, glycated haemoglobin, drug concentrations in tissues and faeces, and the inflammatory and bile acid profiles were measured. Metformin showed wide tissue distribution and was also present in faeces. The bile acid profile showed significant alteration due to prediabetes, and although metformin did not completely normalize it, it did exert significant effects on both the bile acid and the inflammatory profiles, suggesting a direct and, to some extent, positive impact, particularly on the diabetes-associated inflammatory profile.

Keywords: bile acids; cytokines; diabetes mellitus; inflammation; interleukins.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bile Acids and Salts / metabolism
Diabetes Mellitus, Type 2
Disease Models, Animal
Metformin* / pharmacology
Mice
Prediabetic State* / drug therapy
Tumor Necrosis Factors* / metabolism

Substances

Bile Acids and Salts
Tumor Necrosis Factors
Metformin

Grants and funding

The work was partially supported by the European Union Horizon 2020 Research Project and Innovation Program under the Marie Skłodowska-Curie Grant Agreement No. 872370, the Curtin Faculty ORS-WAHAI Consortium, and the Australian National Health and Medical Research (APP9000597). Al-Salami H has been and is currently receiving funding from Beijing Nat-Med Biotechnology Co., Ltd. and Glanis PTY Ltd.