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RETRACTED ARTICLE: A new cationic palladium(II) dithiocarbamate exhibits anti-inflammatory, analgesic, and antipyretic activities through inhibition of inflammatory mediators in in vivo models

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Abstract

Inflammation is being a protective mechanism of the body towards the injury. However, chronic and progressive inflammation may lead to some chronic diseases. Due to the serious unwanted effects associated with available drugs, new and safe anti-inflammatory agents are still required. Therefore, the present study was designed to investigate the anti-inflammatory, analgesics, and antipyretic properties of a new compound (4-benzylpiperidine-1-carbodithioato-κ2S,S′)(1,4-bis-(diphenylphosphino)butane)palladium(II)chloride monohydrate (compound-1) in albino mice models. Compound-1 was characterized by elemental analysis, FT-IR, and multinuclear NMR spectroscopy. Initially, compound-1 was evaluated for cytotoxicity, anti-inflammatory, and analgesic activities by performing MTT assay, carrageenan-, histamine-, serotonin-, and CFA-induced paw edema, mechanical hyperalgesia, thermal hyperalgesia, and mechanical allodynia (0.1, 1, and 10 mg/kg, b.w). Antipyretic activity was evaluated in brewer’s yeast–induced model. The pro-inflammatory cytokines were measured by using commercially available ELISA kits. Additionally, nitrite production, antioxidant enzymes, H&E staining, muscle activity and motor coordination, and kidney and liver function tests were also determined. The results demonstrated that compound-1 significantly inhibited inflammation, pain, and febrile responses in all models at a dose of 10 mg/kg without effecting viability of cells in vitro at concentrations up to 100 μM. Similarly, the data clearly demonstrated significant reduction in the pro-inflammatory cytokines and nitrite production while enhancing antioxidant enzymes. Furthermore, pretreatment with compound-1 did not produce any prominent side effect on kidney, liver, stomach, and muscles. These findings suggest that compound-1 has potent anti-inflammatory-, pain-, and pyrexia-relieving properties. Hence, compound-1 might be a potential candidate for the therapeutic management of chronic inflammation and pain.

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Funding

This work was supported by the Higher Education Commission (HEC), Pakistan under the SRGP funding (No. 357 SRGP/HEC/2014). This work is supported by the National Research Foundation of Korea (NRF) and Seoul National University, grant funded by the Korean Government (MSIP) (No. 2009-0083533).

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Author notes

  1. Muhammad Naveed and Shahan Zeb Khan contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan

    Muhammad Naveed, Sara Zeeshan, Adnan Khan, Bushra Shal, Ayesha Atiq, Hussain Ali & Salman Khan

  2. Department of Chemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan

    Shahan Zeb Khan &  Zia-ur-Rehman

  3. Department of Chemistry, University of Science and Technology, Bannu, KPK, 28100, Pakistan

    Shahan Zeb Khan

  4. Department of Pharmacy, University of Peshawar, Peshawar, Pakistan

    Rahim Ullah

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  1. Muhammad Naveed
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Contributions

MN, AK, BS, and AA designed and performed research including behavioral and biochemical assays. SZK and ZR synthesized the compound. RU and Hussain Ali contributed new reagents and MTT assay. MN, SZ, and SK analyzed the data and drafted the manuscript. SK supervised the project. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Zia-ur-Rehman or Salman Khan.

Ethics declarations

“Animal care guidelines of QAU” Islamabad were followed for the overall procedures involving animals. Bioethical Committee (Approval No. BEC-FBS-QAU 2017-59) of QAU University, Islamabad, approved the study. Maximum care was made sure to minimize harm to animals.

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The authors declare that they have no conflict of interest.

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Naveed, M., Khan, S.Z., Zeeshan, S. et al. RETRACTED ARTICLE: A new cationic palladium(II) dithiocarbamate exhibits anti-inflammatory, analgesic, and antipyretic activities through inhibition of inflammatory mediators in in vivo models. Naunyn-Schmiedeberg's Arch Pharmacol 392, 961–977 (2019). https://doi.org/10.1007/s00210-019-01645-y

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