The therapeutic role of lactobacillus and montelukast in combination with metformin in diabetes mellitus complications through modulation of gut microbiota and suppression of oxidative stress

• Published in: International immunopharmacology Vol. 96; p. 107757
• Main Authors: El-Baz, Ahmed M., Shata, Ahmed, Hassan, Hanan M., El-Sokkary, Mohamed M.A., Khodir, Ahmed E.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2021; Elsevier BV
• Subjects: Acetates - pharmacology; Animals; Apoptosis; BAX protein; Biochemical markers; Caspase-3; Complications; Cyclopropanes - pharmacology; Cytochrome P-450 CYP1A2 Inducers - pharmacology; Damage; Diabetes; Diabetes Complications - etiology; Diabetes Complications - metabolism; Diabetes Complications - pathology; Diabetes Complications - prevention & control; Diabetes mellitus; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - microbiology; Diabetes Mellitus, Experimental - therapy; Disease Models, Animal; Drug Therapy, Combination; E coli; Evaluation; Flora; Gastrointestinal Microbiome; Gut microbiota; Hypoglycemic Agents - pharmacology; Inflammation; Inflammation - drug therapy; Inflammation - immunology; Injuries; Interleukin 17; Intestinal microflora; Lactobacillus; Lactobacillus - chemistry; Lactobacillus - isolation & purification; Lactobacillus - metabolism; Lipids; Liver; Male; Males; Markers; Metformin; Metformin - pharmacology; Microbiota; Modulation; Montelukast; Oxidative stress; Oxidative Stress - drug effects; Quinolines - pharmacology; Rats; Rats, Sprague-Dawley; Relative abundance; Streptozocin; Sulfides - pharmacology; Testes; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Gut microbiota; Montelukast; Metformin; Testes; Diabetes mellitus; Lactobacillus
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2021.107757

•The negative impact of T2DM on the liver and testicles is a major medical concern.•The change in abundance of the gut microbiota is directly correlated to T2DM.•Lactobacillus probiotic has a beneficial role in treating T2DM complications.•Metformin and the anti-inflammatory montelokust are promising tissue protectors.•Lactobacillus plus metformin or montelukast antagonize the apoptotic activity in T2DM. Male reproductive dysfunction is one of the overlooked findings of diabetes mellitus (DM) that deserves greater scientific attention. This study is designed to explore the therapeutic potential of metformin and montelukast, in combination with Lactobacillus, for modulation of intestinal flora and suppression of oxidative stress in testicular and liver damage in diabetic male rats. A DM model was induced by streptozotocin (STZ)which caused functional, biochemical, and inflammatory injuries to the testicular and liver tissues. The experimental panel included nine rat groups: normal control, normal control plus metformin, normal control plus montelukast, DM control, DM plus montelukast, DM plus a combination of metformin and Lactobacillus, DM plus a combination of montelukast and Lactobacillus, and DM plus a combination of metformin and montelukast. In parallel, clinical evaluation of microscopic examination scoring, and hepatic and testicular injuries, were evaluated. Biochemical markers including glucose level, lipid profile, inflammatory markers (tumor necrosis factor- (TNF-α) and interleukin-17 (IL-17), Caspase-3, and Bax proteins expressions were measured. The change in the microbiota abundance was investigated using conventional and real-time PCR. The current study revealed a significant difference in the relative abundance of microbiota, where DM is associated with an enormous increase of Bacteroides spp., Clostridium spp., E. coli, and Fusobacterium spp., and a significant decrease in Bifidobacteria spp., and Lactobacillus spp., in contrast with normal control. Metformin and montelukast, in combination with Lactobacillus, significantly reversed the testicular and liver damage caused by STZ. Moreover, the drugs significantly reduced the oxidative, inflammatory, and apoptotic activities induced by STZ.