This study compared the effects of citric acid (CA) derived from microbial fermentation using Aspergillus niger (400 mg kg-1) and natural extraction from Citrus limon (400 mg kg1) in albino mice. Parameters assessed included cytogenetic damage via the micronucleus (MN) assay, immunological response through immunoglobulin (IgA, IgG, IgM) titers, and hepatoprotective activity based on liver enzyme levels (AST, ALT, ALP) and histopathological investigation. Mice were divided into six groups (n = 10/group) as follows: (1) negative control, (2) carbon tetrachloride (CCl₄ 0.02%), (3) lemon CA, (4) A. niger, (5) CCl₄ + lemon CA, and (6) CCl₄ + A. niger CA. The CCl4 group exhibited a significantly higher MN frequency (0.06 ± 0.008) compared to the control (0.01 ± 0.001). Co-treatment with lemon CA and A. niger CA significantly reduced MN frequencies to 0.02 ± 0.005 and 0.03 ± 0.001, respectively. Immunologically, lemon CA significantly increased IgG and IgM titers but decreased IgA compared to the control. Both CA sources demonstrated hepatoprotective effects, significantly attenuating the CCl4-induced elevation of AST, ALT, and ALP and reducing histopathological damage. The results indicate that while both CAs offer protective benefits, lemon-derived CA was more effective at the tested doses, particularly in mitigating genotoxicity and modulating the immune response.
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