Sodium acetate prevents nicotine-induced cardiorenal dysmetabolism through uric acid/creatine kinase-dependent pathway

O S Michael; C L Dibia; O A Soetan; O A Adeyanju; A L Oyewole; O O Badmus; C O Adetunji; A O Soladoye

doi:10.1016/j.lfs.2020.118127

Sodium acetate prevents nicotine-induced cardiorenal dysmetabolism through uric acid/creatine kinase-dependent pathway

Life Sci. 2020 Sep 15:257:118127. doi: 10.1016/j.lfs.2020.118127. Epub 2020 Jul 22.

Authors

O S Michael¹, C L Dibia², O A Soetan³, O A Adeyanju⁴, A L Oyewole⁵, O O Badmus⁶, C O Adetunji⁷, A O Soladoye⁸

Affiliations

¹ Cardiometabolic Research Unit, Department of Physiology, College of Health Sciences, Bowen University, Iwo, Nigeria; HOPE Cardiometabolic Research Team, Department of Physiology, University of Ilorin, Ilorin, Nigeria; Bioscience Research Hub, Ilorin, Nigeria. Electronic address: olugbenga.michael@bowen.edu.ng.
² HOPE Cardiometabolic Research Team, Department of Physiology, University of Ilorin, Ilorin, Nigeria; Department of Physiology, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria.
³ HOPE Cardiometabolic Research Team, Department of Physiology, University of Ilorin, Ilorin, Nigeria.
⁴ HOPE Cardiometabolic Research Team, Department of Physiology, University of Ilorin, Ilorin, Nigeria; Bioscience Research Hub, Ilorin, Nigeria; Cardiometabolic Research Unit, Department of Physiology, College of Health Sciences, Afe-Babalola University, Ado-Ekiti, Nigeria.
⁵ Bioscience Research Hub, Ilorin, Nigeria; Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria.
⁶ HOPE Cardiometabolic Research Team, Department of Physiology, University of Ilorin, Ilorin, Nigeria; Department of Public Health, Kwara State University, Malete, Kwara State, Nigeria.
⁷ Microbiology, Biotechnology and Nanotechnology Laboratory, Department of Microbiology, Edo University, Iyamho, Edo State, Nigeria.
⁸ Cardiometabolic Research Unit, Department of Physiology, College of Health Sciences, Bowen University, Iwo, Nigeria; HOPE Cardiometabolic Research Team, Department of Physiology, University of Ilorin, Ilorin, Nigeria.

PMID: 32707052
DOI: 10.1016/j.lfs.2020.118127

Abstract

Background: Cigarette smoking or nicotine replacement therapy has been associated with cardiometabolic disorders (CMD). Hyperuricemia has been implicated in the pathogenesis of CMD and cardiorenal dysfunction. Gut microbiota-derived short chain fatty acids (SCFAs) have been reported to have beneficial glucoregulatory and cardiorenal protective effects. This study aimed at investigating the effect of acetate, a gut-derived SCFA, on nicotine-induced CMD and associated cardiorenal dysmetabolism.

Materials and method: Twenty-four male Wistar rats (n = 6/group) were grouped as: vehicle (p.o.), nicotine-exposed (1.0 mg/kg; p.o.), and sodium acetate-treated (200 mg/kg; p.o.) with or without nicotine exposure daily for 6 weeks. Glucose regulation was evaluated by oral glucose tolerance test and homeostatic model assessment of insulin resistance. Cardiac and renal triacylglycerol (TG), lactate, nitric oxide (NO), uric acid (UA) levels, lactate dehydrogenase (LDH), creatine kinase (CK), adenosine deaminase (ADA), and xanthine oxidase (XO) activities were measured.

Results: The CMD were confirmed in the nicotine-exposed rats that exhibited lower body weight, insulin resistance, endothelial dysfunction, glucose intolerance, increased cardiac and renal TG, TG/HDL-cholesterol, UA, lactate, lipid peroxidation, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, LDH, CK, ADA and XO activities. Concurrent treatment with acetate prevented nicotine-induced glucometabolic and cardiorenal alterations.

Conclusion: In summary, these results implied that nicotine exposure caused glucometabolic dysregulation and surplus lipid deposit in the heart and kidney through increased UA production and CK activity. Therefore, oral acetate administration prevents cardiorenal lipotoxicity and glucometabolic dysregulation via suppression of UA production and CK activity in nicotine-exposed rats.

Keywords: Acetate; Cardiorenal lipid accumulation; Creatine kinase; Nicotine; Uric acid; Xanthine oxidase.

MeSH terms

Animals
Creatine Kinase / metabolism*
Glucose / metabolism
Glucose Tolerance Test
Heart / drug effects*
Insulin Resistance
Kidney / drug effects*
Kidney / metabolism
Male
Metabolic Networks and Pathways / drug effects*
Myocardium / metabolism*
Nicotine / adverse effects*
Nicotine / antagonists & inhibitors
Rats
Rats, Wistar
Sodium Acetate / pharmacology*
Uric Acid / metabolism*

Substances

Uric Acid
Sodium Acetate
Nicotine
Creatine Kinase
Glucose