Affiliation:
1. Department of Genetics, Cytology and Bioengineering, Voronezh State University, 394018 Voronezh, Russia
2. Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technology, 394036 Voronezh, Russia
Abstract
L-carnitine plays a critical role in sperm functioning and maintaining male fertility. Mildronate is a widely used drug for treating cardiovascular diseases. Mildronate inhibits L-carnitine biosynthesis and transport into cells while increasing glucose supply. Therefore, it is speculated that mildronate may impair male fertility by depleting L-carnitine. On the other hand, mildronate is known to have anti-inflammatory effects, which can positively influence the male reproductive system in certain physiological conditions. In this study, we induced inflammation in mice through lipopolysaccharide (LPS) injections and examined some inflammation markers in the testes and intestine, which contribute significantly to the development of systemic inflammation. We demonstrated that mildronate reduces inflammation in mouse testes and preserves mitochondrial DNA integrity. Importantly, mildronate-induced L-carnitine depletion did not have a negative impact on testicular properties or sperm count. We propose that the anti-inflammatory effect of mildronate may be linked to its action on the bacterial composition of the gut microbiome. Mildronate increases the Firmicutes/Bacteroidetes ratio, which is reduced after LPS injections. In contrast to L-carnitine supplementation, mildronate does not decrease the level of Alloprevotella, a bacterial genus that is necessary for reducing inflammation. Additionally, mildronate decreased the expression of pro-inflammatory cytokines and inflammation markers in the intestine, which aligns with our hypothesis regarding its anti-inflammatory effect.
Funder
Ministry of Science and Higher Education of the Russian Federation
President of the Russian Federation for young scientists and graduate students
Subject
Gastroenterology,Oncology,Immunology and Microbiology (miscellaneous),Hepatology