Effects of Antibiotics Overuse and Misappropriation on Gut Microbes, Induced Inflammation and Oxidative Stress in a Murine Model
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Date
2023-10
Authors
Langatt, Winnie Chepkirui
Journal Title
Journal ISSN
Volume Title
Publisher
Kenyatta University
Abstract
Antibiotics are among the most misused drugs in Kenya and across the globe. This occurs despite existence of regulation measures. Antibiotic misuse is associated with deleterious events that interfere with the gut microbiota. Despite the importance of antibiotics, the effects of their overuse and misuse on gut microbes, elicited inflammation and oxidative stress remains an enigma. Therefore, investigations were conducted to unravel the impact of antibiotic-induced dysbiosis on gut microbes, induced oxidative stress and inflammation using murine model. In this study, one group of Swiss White mice was used as normal control; group two received 9.62 mg/kg amoxicillin, group three received 17.53 mg/kg amoxicillin with clavulanic acid, group four received 15.38 mg/kg azithromycin,group five received azithromycin-amoxicillin-amoxicillin with clavulanic acid successively (successive antibiotics) and group six received successive antibiotics with probiotics and was used as the positive control. A series of biochemical and physiological analyses were carried out in concert with the study objectives. Rapid murine coma and behavioural scale (RMCBS), full blood heamogram, body and organ weights were employed to assess the effects of antibiotics on various physiological parameters. In addition, lipid profiles, liver function assays, reduced glutathione assay and cytokine sandwich enzyme-linked immunosorbent assay (ELISA) were utilized to determine the effects of antibiotics on induction of oxidative stress and inflammation. Lastly, histological studies were carried out on the kidney, brain, small intestine, and liver to further evaluate the effects of antibiotics on induction of inflammation. Results from this study demonstrated that there was a significant reduction in body weights of experimental groups of mice. The RMCBS analysis showed that mice treated with antibiotics exhibited neurological deficiencies. Moreover, there was significant reduction in haematocrit, red blood cell and haemoglobin count in mice administered with successive antibiotics relative to the untreated group of mice. A significant increase in white blood cell levels in mice given 9.62 mg/kg of amoxicillin was exhibited. Particularly, the lymphocytes and the monocytes were highly augmented. Meanwhile, the successive use of antibiotics resulted in elevated levels of aspartate amino transferase (AST) and alanine amino transferase (ALT) signalling liver damage. Lipid profiles showed that amoxicillin treated mice depicted a significant decline in total serum cholesterol and serum high density lipoproteins (HDL). Additionally, the successive use of antibiotics resulted in disrupted cellular glutathione (GSH) in brain, kidney, heart, lungs, liver and gut, a strong signal of active oxidative stress. Serum samples showed augmented tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) in mice that were under successive use of antibiotics. Liver and kidney injury resulted as per histopathological analysis in the groups administered with 9.62 mg/kg amoxicillin, 17.53 mg/kg amoxicillin/clavulanic acid and the successive antibiotics. Findings from this study give compelling evidence that amoxicillin, amoxicillin/clavulanic acid and azithromycin when used alone or successively with other antibiotics results in dysbiosis and organ damage. In addition, they interfere with the immune response by enhancing inflammatory processes, while inducing oxidative stress. Consequently, this study recommends assessment of physiological, biochemical, histological parameters during antibiotic use. Furthermore, it recommends prescription of antibiotics along with immune boosters, antioxidants and probiotics. Importantly, tightening of regulations pertaining to dispensation of antibiotics both by pharmacists and physicians ought to be implemented.
Description
A Thesis Submitted in Partial Fulfilment of the Requirements for the Award of the Degree of Master of Science (Biochemistry) in the School of Pure and Applied Sciences of Kenyatta University, October 2023.
Keywords
Antibiotics Overuse, Gut Microbes, Induced Inflammation, Oxidative Stress, Murine Model