Mansouri RA, Aboubakr EM, Alshaibi HF, Ahmed AM. L-arginine administration exacerbates myocardial injury in diabetics via prooxidant and proinflammatory mechanisms along with myocardial structural disruption. World J Diabetes 2025; 16(2): 100395 [DOI: 10.4239/wjd.v16.i2.100395]
Corresponding Author of This Article
Esam M Aboubakr, Doctor, PhD, Associate Professor, Department of Pharmacology and Toxicology, Faculty of Pharmacy-South Valley University, Qena-afaga Road, Qena 83523, Egypt. esam_pharma@svu.edu.eg
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Diabetes. Feb 15, 2025; 16(2): 100395 Published online Feb 15, 2025. doi: 10.4239/wjd.v16.i2.100395
L-arginine administration exacerbates myocardial injury in diabetics via prooxidant and proinflammatory mechanisms along with myocardial structural disruption
Rasha A Mansouri, Esam M Aboubakr, Huda F Alshaibi, Adel M Ahmed
Rasha A Mansouri, Huda F Alshaibi, Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah 22254, Jeddah, Saudi Arabia
Rasha A Mansouri, College of Science and Humanities in Al-Kharj, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
Esam M Aboubakr, Department of Pharmacology and Toxicology, Faculty of Pharmacy-South Valley University, Qena 83523, Egypt
Huda F Alshaibi, Stem Cell Unit, King Fahad Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Adel M Ahmed, Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, South Valley University, Qena 83523, Egypt
Author contributions: Aboubakr EM and Ahmed AM were responsible for statistical analysis of the data, drafted and revised the manuscript and contributed to the conception and design of this article; Mansouri RA and Alshaibi HF contributed to the case collection and database organization; Mansouri RA and Ahmed AM interpreted the results, have contributed equally to this work as co-first authors. They both played a critical role in literature reviews, data collection and analysis as well as composition writing. Aboubakr EM and Alshaibi HF have contributed equally to this work. They both provided guidance and supervision to the design of this study. All authors read and approved the final manuscript.
Supported by The Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia, No. IF2/PSAU/2022/03/23339.
Institutional review board statement: The Faculty of Pharmacy Ethical Committee at South Valley University has approved the research project, which provided by Dr/ Esam M. Aboubakr, which study the effect of L arginine administration on the cardiac muscle of diabetic rats.
Institutional animal care and use committee statement: This study was reviewed and approved by the Faculty of Pharmacy Ethical Committee at South Valley University (protocol # P.S.V.U 230) for the use of animals.
Conflict-of-interest statement: The authors declare that they have no Conflict of interest.
Data sharing statement: Raw data can be obtained by contacting the corresponding author.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Esam M Aboubakr, Doctor, PhD, Associate Professor, Department of Pharmacology and Toxicology, Faculty of Pharmacy-South Valley University, Qena-afaga Road, Qena 83523, Egypt. esam_pharma@svu.edu.eg
Received: August 15, 2024 Revised: October 2, 2024 Accepted: November 25, 2024 Published online: February 15, 2025 Processing time: 137 Days and 7.2 Hours
Abstract
BACKGROUND
L-arginine (L-Arg) is one of the most widely used amino acids in dietary and pharmacological products. However, the evidence on its usefulness and dose limitations, especially in diabetics is still controversial.
AIM
To investigate the effects of chronic administration of different doses of L-Arg on the cardiac muscle of type 2 diabetic rats.
METHODS
Of 96 male rats were divided into 8 groups as follows (n = 12): Control, 0.5 g/kg L-Arg, 1 g/kg L-Arg, 1.5 g/kg L-Arg, diabetic, diabetic + 0.5 g/kg L-Arg, diabetic + 1 g/kg L-Arg, and diabetic + 1.5 g/kg L-Arg; whereas L-Arg was orally administered for 3 months to all treated groups.
RESULTS
L-Arg produced a moderate upregulation of blood glucose levels to normal rats, but when given to diabetics a significant upregulation was observed, associated with increased nitric oxide, inflammatory cytokines, and malonaldehyde levels in diabetic rats treated with 1 g/kg L-Arg and 1.5 g/kg L-Arg. A substantial decrease in the antioxidant capacity, superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione concentrations, and Nrf-2 tissue depletion were observed at 1 g/kg and 1.5 g/kg L-Arg diabetic treated groups, associated with myocardial injury, fibrosis, α-smooth muscle actin upregulation, and disruption of desmin cardiac myofilaments, and these effects were not noticeable at normal treated groups. On the other hand, L-Arg could significantly improve the lipid profile of diabetic rats and decrease their body weights.
CONCLUSION
L-Arg dose of 1 g/kg or more can exacerbates the diabetes injurious effects on the myocardium, while 0.5 g/kg dose can improve the lipid profile and decrease the body weight.
Core Tip: L-arginine (L-Arg) is commonly used amino acid with many physiological effects, but its safety and pharmacological effects are not fully understood and still controversial. This study found that a dose of 0.5 g/kg of L-Arg appears to be the highest dose that can be safely administered without producing cardiac damage in diabetic rats. However, doses of 1 g/kg or higher can worsen myocardial damage by increasing blood glucose levels, inflammation, and oxidative stress. L-Arg can also reduce body weight and improve lipid levels in rats, but these benefits do not outweigh the injurious effects of high doses on the cardiac muscle.
