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Screening impacts of Tilmicosin-induced hepatic and renal toxicity in rats: protection by Rhodiola rosea extract through the involvement of oxidative stress, antioxidants, and inflammatory cytokines biomarkers

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Abstract

Tilmicosin (TIL) is a semisynthetic macrolide antibiotic with a broad spectrum of activity derived from tylosin. TIL is effective in the treatment of bovine and ovine respiratory diseases caused by different microbes. In parallel, Rhodiola rosea (RHO) is a popular herbal remedy because of its anti-inflammatory and antioxidant qualities. The experiment lasted for 12 days. Depending on the experimental group, the animals received either distilled water or RHO root extract dissolved in distilled water for 12 days through a stomach tube, and the single subcutaneous injection on day 6 of the experiment of either 500 μL of 0.9% NaCl or TIL dissolved in 500 μL 0.9% NaCl. Samples and blood were collected for serum analysis, gene expression, and immunohistochemistry screening at liver and kidney levels. TIL injection increased serum levels of hepatic and renal markers (ALP, ALT, AST, TC, TG, creatinine, and urea) with decreased total proteins. In parallel, TIL induced hepatic and renal oxidative stress as there was an increase in malondialdehyde levels, with a decrease in catalase and reduced glutathione activities. Of interest, pre-administration of RHO inhibited TIL-induced increase in hepato-renal markers, decreased oxidative stress, and increased liver and kidney antioxidant activities. Quantitative RT-PCR showed that TIL increased the liver’s HSP70 (heat shock protein), NFkB, and TNF-α mRNA expression. Moreover, TIL upregulated the expression of desmin, nestin, and vimentin expression in the kidney. The upregulated genes were decreased significantly in the protective group that received RHO. Serum inflammatory cytokines and genes of inflammatory markers were affected in liver tissues (HSP70, NFkB, and TNF-α) and kidney tissues (desmin, nestin, and vimentin)—TIL-induced hepatic vacuolation and congestion together with glomerular atrophy. The immunoreactivity of PCNA and HMGB1 was examined immunohistochemically. At cellular levels, PCNA was decreased while HMGB1 immunoreactivity was increased in TIL-injected rats, which was improved by pre-administration of RHO. RHO administration protected the altered changes in liver and renal histology. Current findings support the possible use of RHO to shield the liver and kidney from the negative effects of tilmicosin.

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Acknowledgements

The authors extend their appreciation to Taif University, Saudi Arabia, for supporting this work through project number (TU-DSPP-2024-24). The authors would like to thank the Pathology, Pharmacology, and Clinical Pathology Departments, Faculty of Medicine at Benha University, Egypt, for their invaluable technical and administrative support throughout this work.

Funding

This research was funded by Taif University, Saudi Arabia, Project No. (TU-DSPP-2024-24).

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, Benha University, Benha, 13511, Egypt

    Salwa A. Elgendy & Heba A. Elnoury

  2. Department of Clinical Laboratory Sciences, Turabah University College, Taif University, P.O. Box 11099, 21944, Taif, Saudi Arabia

    Mohamed Mohamed Soliman

  3. Department of Physiology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, 33516, Egypt

    Mustafa Shukry

  4. Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Benha University, Benha, 13511, Egypt

    Lina Abdelhady Mohammed & Hend Elsayed Nasr

  5. Department of Biology, Turabah University College, Taif University, Taif, 21995, Saudi Arabia

    Saad Althobaiti

  6. Biology Department, Faculty of Science and Arts, Al-Mikhwah, Al-Baha University, Al-Baha, Saudi Arabia

    Daklallah A. Almalki

  7. General Science and English Language Department, College of Applied Sciences, AlMaarefa University, Riyadh, Saudi Arabia

    Khalid S. Alotaibi & Shatha B. Albattal

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  1. Salwa A. Elgendy
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Contributions

Salwa Elgendy, Heba Elnoury and Mostafa Shukry: Methodology, Investigation, Formal analysis, Visualization, Writing–original draft preparation. Saed Althobaiti, Lina Mohammed, Hend Nasr and Khalid Alotaibi: Validation. Investigation, Formal analysis. Daklallah Almalki and Shatha Alnattal: Investigation, Formal analysis, and Visualization. Mohamed Soliman, Salwa Elgendy and Mostafa Shukry: Conceptualization, Supervision, Validation, Writing. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Mohamed Mohamed Soliman.

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Elgendy, S.A., Soliman, M.M., Shukry, M. et al. Screening impacts of Tilmicosin-induced hepatic and renal toxicity in rats: protection by Rhodiola rosea extract through the involvement of oxidative stress, antioxidants, and inflammatory cytokines biomarkers. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-03089-5

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