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The anti-inflammatory effects of minocycline on lipopolysaccharide-induced paw oedema in rats: a histopathological and molecular study

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Abstract

Minocycline is a semi-synthetic antimicrobial agent with claimed anti-inflammatory properties reported from different experimental models. This study was aimed to evaluate the anti-inflammatory effects of minocycline, compared to the actions of two common anti-inflammatory agents, on lipopolysaccharide (LPS)-induced paw oedema through some clinical, histopathological, haematological and molecular analyses. Forty-eight rats were divided into eight groups (n = 6). In control group (Ctrl), each animal was injected with normal saline into its sub-plantar region of hind paw. In groups 2–7, hind paw oedema was induced by injection of LPS. One hour before injections, groups 1 (Ctrl) and 2 (LPS) were treated orally with distilled water, 3 and 4 with methylprednisolone (Pred) and meloxicam (Melo) and 5–7 with minocycline in doses of 50, 150 and 450 mg/kg (M50, M150 and M450, respectively). The 8th group (MC) was given minocycline (150 mg/kg) orally and normal saline was injected into sub-plantar region. Paw swelling and body temperature were assessed at 0, 2, 4, 6 and 24 h post-injections. At 24 h, samples of blood and liver, kidney, spleen and hind paw tissues were taken for haematological and histopathological examinations. Some samples of the paw were also obtained for molecular analysis of some inflammatory-related cytokines at mRNA level. Paw swelling and body temperature increased in all LPS-injected groups 2 h post-injection. In LPS group, they remained significantly increased up to 24 h; however, these parameters decreased to normal in Pred, Melo and all minocycline groups. The histological findings showed mild-to-moderate signs of inflammation in tissue samples of groups 2–6, but not in group M450. Additionally, gene expression of pro-inflammatory cytokines (IL-1β and IL-6) increased significantly in LPS group compared to other groups. In conclusion, this study supports the role of minocycline as an anti-inflammatory agent with effects comparable to those of meloxicam and methylprednisolone.

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Acknowledgements

Authors wish to thank Dr. V. Siavoshi, Dr.H. Akbarein, and S. Yousefi for their assistance.

Funding

It is declared that a partial financial support for the PhD thesis of Basim Shihmani was made by Research Deputy, Faculty of Veterinary Medicine, University of Tehran.

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Authors and Affiliations

  1. Pharmacology Division, Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, 1419963114, Iran

    Basim Shihmani & Ali Rassouli

  2. Department of Microbiology and Immunology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

    Jalil Mehrzad

  3. Department of Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

    Sara Shokrpoor

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All authors contributed to the study conception and design as well as material preparation, data collection and analysis. The first draft of the manuscript was written by BS, AR and SS and then all authors commented on the first draft. All authors read and approved the final manuscript.

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Correspondence to Ali Rassouli.

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This study was approved by Research Committee including Ethics Committee of the Research Deputy, Faculty of Veterinary Medicine, University of Tehran (IACUC-approved project No.7506006/6/11).

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Shihmani, B., Rassouli, A., Mehrzad, J. et al. The anti-inflammatory effects of minocycline on lipopolysaccharide-induced paw oedema in rats: a histopathological and molecular study. Inflammopharmacol 31, 1913–1928 (2023). https://doi.org/10.1007/s10787-023-01236-7

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