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Ameliorative effects of Dictyota dichotoma on hepatotoxicity induced by gibberellic acid in albino rats

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Abstract

Gibberellic acid (GA3) is a natural plant growth regulator that is crucial for plant structural and functional development. We examined the alleviating capacity of brown algae (Dictyota dichotoma) on biochemical and molecular degenerative processes caused by sub-chronic exposure to gibberellic acid resulting in hepatic cell apoptosis. Adult male albino rats were divided into five equal groups: the first group received distilled water, the second group was treated with GA3, the third group was administered D. dichotoma extract suspended in 1% carboxymethylcellulose (CMC), the fourth group was administered both GA3 and D. dichotoma simultaneously, and the fifth group received 1% CMC orally, 5 days per week for a total of 50 days. The results indicated that GA3 induced a significant increase in liver function parameters based on serum levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin, which indicate hepatotoxicity. A marked increase in malondialdehyde (MDA) levels and a marked decrease in reduced glutathione (GSH), glutathione-S-transferase (GST), and superoxide dismutase (SOD) were observed as a result of induction of lipid peroxidation and oxidative stress. Histopathology revealed severely degenerated hepatocytes including cytoplasmic vacuolations and many apoptotic cells with weak Bcl2 expression. Similarly, there was a significant up-regulation of gene and protein expression levels for the pro-apoptotic markers, Caspase-3 and Bax, and an increase in pro-inflammatory marker levels, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) as well as C-reactive protein (CRP). The co-administration of D. dichotoma restored the disrupted biochemical, histopathological, molecular, and inflammatory changes resulting from GA3 toxicity. Our results confirm the antioxidant, anti-inflammatory, anti-apoptotic, and hepatoprotective potential of D. dichotoma.

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Abbreviations

ALT:

Alanine aminotransferase

ALP:

Alkaline phosphatase

AST:

Aspartate aminotransferase

CMC:

Carboxymethylcellulose

CRP:

C-reactive protein

GSH:

Glutathione

GST:

Glutathione-S-transferase

IL-6:

Interleukin-6

MDA:

Malondialdehyde

qRT-PCR:

Quantitative real time-polymerase chain reaction

SD:

Standard deviation

SOD:

Superoxide dismutase

TNF-α:

Tumor necrosis factor-alpha

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Acknowledgements

We would like to thank Dr. Doaa Ramadan Ismail, Dr. Ahlam Gamal Khalifa, Dr. Shaimaa Emad Hasssan, and Dr. Ola Gomaa Hussin for their substantial help in the lab work. This work was supported by the Science, Technology and Innovation Funding Authority under Grant number RSY 42932.

Funding

 This work was supported by the Science, Technology and Innovation Funding Authority under Grant number RSY 42932.

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Authors and Affiliations

  1. Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, 62511, Egypt

    Shaimaa Ali, Walaa A. Moselhy & Kh. Abdou

  2. Genetic and Molecular Biology, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt

    Hanaa M. Mohamed

  3. Department of Cytology and Histology, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, 62511, Egypt

    Taghreed M. Nabil

  4. Department of Pharmacology, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, 62511, Egypt

    Fatma I. Abo El-Ela

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  1. Shaimaa Ali
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Ali, S., Moselhy, W.A., Mohamed, H.M. et al. Ameliorative effects of Dictyota dichotoma on hepatotoxicity induced by gibberellic acid in albino rats. Toxicol Res. 38, 379–392 (2022). https://doi.org/10.1007/s43188-022-00122-8

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  • DOI: https://doi.org/10.1007/s43188-022-00122-8

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