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Nano-chitosan/bovine lactoperoxidase and lactoferrin formulation modulates the hepatic deterioration induced by 7,12-dimethylbenz[a]anthracene

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Abstract

Lactoperoxidase (LPO) and lactoferrin (LF) are promising bovine proteins that can be nano-formulated with chitosan nanoparticles giving a potent pharmaceutical product. This study aimed to evaluate the therapeutic potential of a prepared nano-combination composed of LPO and LF loaded on chitosan nanoparticles (LPO + LF/CNPs) against oxidative damage in the liver of rats exposed to 7,12-dimethylbenz[a]anthracene (DMBA). Twenty-four male Wistar albino rats (4 months old) were divided into three equal groups and treated orally as follow: (1) rats were given saline and served as control, (2) rats received a single dose (20 mg/kg) of DMBA dissolved in soy oil, and (3) rats intoxicated with a single dose (20 mg/kg) of DMBA, 56 days prior to their oral treatment with the nano-combination (50 mg /kg/day) for consecutive 30 days. Then, blood and liver samples were collected for biochemical determinations. Histological and immunohistochemistry examinations of liver tissue were also performed. TEM image of LPO + LF/CNPs showed semi-rounded shape particles with an average size of 336.8 nm and 47.30 mV zeta potential. DMBA intoxication increased serum aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and gamma-glutamyl transferase (GGT) activities. DMBA increased also the values of hepatic malondialdehyde (MDA) and nitric oxide (NO), serum nuclear factor κB (NF-κB), caspase-3, interleukin-1beta (IL-1β), and tumor necrosis factor-alpha (TNF- α), and the tumor markers alpha fetoprotein (AFP) and carcino embryonic antigen (CEA), whereas hepatic glutathione (GSH) content and the activities of hepatic glutathione peroxidase (GPx), catalase (CAT), and glutathione–S-transferase (GST) were significantly decreased. In addition, serum triglycerides, total, and low-density lipoprotein cholesterol (LDL-C) levels were significantly elevated with a significant decrease in high-density lipoprotein cholesterol (HDL-C) and albumin levels. Moreover, DMBA induced severe histological alterations in the liver tissue and the immunohistochemistry investigation revealed that DMBA exposure upregulated the hepatic protein expression of caspase 3. The post-treatment with LPO + LF/CNPs ameliorated most of the above parameters and improved the histological picture of the liver. The present study indicated that LPO + LF/CNPs have a potent therapeutic potential against DMBA hepatotoxicity through the suppression of oxidative stress and inflammation which leads to liver damage.

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Acknowledgements

The authors would like to thank Medical Physiology and Dairy Departments, National Research Centre; Zoology Department, Faculty of Science, Alzhar University; Histology Department, Faculty of Dentistry, Sainai University; and Protein Research Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), City of Scientific Research and Technological Applications (SRTA-City) for their kindly cooperation.

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Authors and Affiliations

  1. Medical Physiology Department, National Research Centre, Giza, Egypt

    Khaled G. Abdel-Wahhab, Ghada M. Elqattan & Fathia A. Mannaaa

  2. Zoology Department, Faculty of Science, Al Azhar University, Assiut, Egypt

    Mahmoud Ashry

  3. Dairy Department, National Research Centre, Giza, Egypt

    Laila K. Hassan

  4. Histology Department, Faculty of Dentistry, Sainai University, Kantara, Egypt

    Mohamed H. A. Gadelmawla

  5. Protein Research Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), City of Scientific Research and Technological Applications (SRTA-City), New Borg El-Arab City, Alexandria, Egypt

    Esmail M. El-Fakharany

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Abdel-Wahhab, K.G., Ashry, M., Hassan, L.K. et al. Nano-chitosan/bovine lactoperoxidase and lactoferrin formulation modulates the hepatic deterioration induced by 7,12-dimethylbenz[a]anthracene. Comp Clin Pathol 32, 981–991 (2023). https://doi.org/10.1007/s00580-023-03510-0

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