Biochemistry

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    Effects of co-trimoxazole and amoxicillin therapy on gut microbiota population, physiological, biochemical and pathological parameters in Swiss mice
    (Chuka University, 2024) Kiptoo Kamngoror Cosmas
    Antibiotics have been utilized in treatment of bacterial infections since their discovery. Despite being beneficial in managing infections, antibiotics have significant implications on health by disrupting the gut microbiota. Gut microbiota comprises of wide range of microorganisms that inhabit the gut, including fungus, archaea, bacteria, and viruses. The gut microbiota plays pivotal role in health by influencing metabolic processes, immunological and neurobehavioral functions. This study investigated the impact of amoxicillin and co-trimoxazole on the gut bacterial population of mice, using three-week-old Swiss mice models simulating six-month-old human babies. The experiment aimed to assess physiological, biochemical, immuno-pathological changes, and the induction of oxidative stress. Male swiss mice were randomly assigned to five groups: normal control, amoxicillin group, septrin group, amoxicillin+septrin group, and amoxicillin+co-trimoxazole+probiotics. Over 63 days, mice were monitored, weighed after each antibiotic dosage. Euthanasia was performed using isoflurane, and blood samples was collected via cardiac puncture for hematological analysis. The liver, spleen, kidney, lungs and heart were harvested and weighed for determination relative organ weight (ROW), liver, brain and kidneys were harvested for histo-pathological examination. Serum obtained from whole blood underwent further analysis for various markers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatinine, urea and cytokines. Tissue glutathione (GSH) and malondialdehyde (MDA) levels, along with serum nitric oxide (NO), were determined to gauge oxidative stress. Numeric data underwent analysis using one-way ANOVA followed by Tukeys' post hoc test, with significance reported at p<0.05. Results, in form of graphs and images, revealed amoxicillin and septrin administered singly or in combination resulted in reduced gut microbiota population resulting in gut microbiota dysbiosis. Probiotics administration ameliorated the gut microbiota dysbiosis. There were no significant changes in body weight as well as relative organ weight (ROW) of the selected organs. Hematological exams revealed significant drop in the red blood cells (RBCs) count, hematocrit level and hemoglobin especially in amoxicillin+septrin treated group. White blood cells count (WBCs) was significantly elevated in septrin group compared to control, amoxicillin group, amoxicillin+septrin treated group and amoxicillin+septrin+probiotics treated group. Liver function test markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST:ALT ratio and alkaline phosphate (ALP), were significantly (p<0.05) elevated indicating liver damage. Kidney function markers showed elevated levels of creatinine, urea, uric acid and significant drop in the levels of albumin indicating kidney damage. Gut microbiota dysbiosis results in electrolyte imbalances noted by a drop in the levels of serum electrolytes; sodium, chloride and potassium. There were significant (p<0.05) elevated levels of interferon gamma (IFN-γ), tumor necrotic factor alpha (TNF-α) indicating active inflammation, histological exams revealed tissue damage in the liver and kidneys, and oxidative stress indicated by elevated malondialdehyde (MDA) and glutathione (GSH) levels in target organs. There were significant (p<0.05) elevated nitric oxide (NO) levels in the serum indicating active inflammation or damage to organ functions. Probiotics administration alongside antibiotics showed promising outcomes, by restoring gut microbiota population and consequently protecting the body from induction of immunological responses and inflammation, protection from oxidative stress and organ damage suggesting a potential avenue for ameliorating complications associated with antibiotic-induced dysbiosis. This comprehensive study highlights the intricate effects of antibiotics on gut microbiota and associated health parameters, emphasizing the need for cautious antibiotic use to mitigate potential adverse outcomes.
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    Quantitative phytochemical composition, antipyretic and antioxidative effects of methanolic leaf and root extracts of Carica papaya Linn.
    (Chuka University, 2025) Tarus, Everlyne Jebiwott
    Antipyrexia and oxidative stress-related conditions are significant global health issues due to their widespread impacts on human health and well-being. Fever is mostly triggered by infectious stimuli and is characterized with increase in temperatures typically above the normal range for human, (36.5–37.5 °C). Currently, fever is treated with traditional methods such as active cooling and conventional medications such as Nonsteroidal Anti-inflammatory Drugs (NSAIDs) and paracetamol. It has been documented that NSAIDs have adverse effects on the cardiovascular, hepatic, renal, and gastric mucosa systems. On the other hand, oxidative stress contributes to the pathogenesis of a many chronic and degenerative disorders. Conventional antioxidants have been reported to be less effective and relatively expensive. Due to these draw backs, there is a need to research for alternative method for the management of fever and oxidative stress, including the use of herbal medicines. Carica papaya has been known to be used traditionally in treating fever and conditions associated with oxidative stress, but concrete evidence on its medicinal value is limited. Thus, this study evaluated phytochemical profiles, antipyretic and antioxidative effects of methanolic leaf and root extracts of Carica papaya. Leaves and roots of C. papaya were collected from Karingani ward, Chuka-Igambang’ombe sub-county, Tharaka Nithi County, Kenya. The plant materials were extracted methanol. Quantitative phytochemical screening was done using GC-MS. The in-vivo antipyretic activities of the extract were screened in thirty male white albino Wistar rats weighing 90-150g. Turpentine was used to induce fever in rats. Antioxidant activity of the methanol leaf and root extracts was evaluated using non-enzymatic antioxidant assays. The GC–MS analysis of methanolic root and leaf extracts of Carica papaya revealed the bioactive phytochemicals incluiding flavonoids (quercetin) phenolic(caffeic),terpenes and terpenoids (squalene, myrcene), vitamin C (Ascorbic acid), fatty acid (n-hexadecanoic), and alkaloids (reserpinine). The methanolic root and leaf extracts of Carica papaya showed dose and time-dependent antipyretic activity. The temperature reduction of the root extract in the first hour was 1.15%, 1.77%, and 2.20% and second hour 3.83%, 4.32%, and 4.30% (50, 100, and 150 mg/kg; respectively, comparable to paracetamol (1.57%, 3.72% in the first and second hour respectively. At the third and fourth hours, reductions reached 5.25%, 5.68%, and 5.08%, and 5.20%, 5.84%, and 5.13%, respectively, statistically similar to paracetamol (4.82% in the third hour and 5.30% in the fourth hour). The leaf extract percentage reduction in the first hour was 0.73%, 1.87%, and 1.57%, (50, 100, and 150 mg/kg; respectively, comparable to paracetamol (1.57%). At the second hour, significant decreases of 2.50%, 4.22%, and 3.93% were observed, with the higher doses showing effects similar to the positive control (3.72%). By the third hour, the extract reduced by 3.77%, 4.70%, and 4.77%, and paracetamol (4.82%). At the fourth hour, the reductions were 4.25%, 5.16%, and 5.30%, and statistically comparable to the positive control (5.30%). The root extract showed greater antipyretic effects as compared the leaf extract at lower doses. At higher doses both extracts were similarly effective. Carica papaya indicated in vitro antioxidant effects in all the tested non-enzymatic assays. The results from the study indicates that C. papaya is a potent natural therapeutic alternative for management of fever and oxidative stress related conditions.