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

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2019-08, Vol.392 (8), p.961-977
• Main Authors: Naveed, Muhammad, Khan, Shahan Zeb, Zeeshan, Sara, Khan, Adnan, Shal, Bushra, Atiq, Ayesha, Ali, Hussain, Ullah, Rahim, Zia-Ur-Rehman, Khan, Salman
• Format: Article
• Language: English
• Subjects: Analgesics; Analgesics, Non-Narcotic - pharmacology; Animal models; Animals; Anti-inflammatory agents; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Antioxidants; Antioxidants - metabolism; Antipyretics - pharmacology; Behavior, Animal - drug effects; Butane; Carrageenan; Cell Survival - drug effects; Chronic illnesses; Cytokines; Cytokines - metabolism; Cytotoxicity; Edema; Edema - chemically induced; Edema - prevention & control; Enzyme-linked immunosorbent assay; Enzymes; Fever; Fever - chemically induced; Fever - prevention & control; Histamine; Hyperalgesia; Hyperalgesia - prevention & control; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Inflammation - psychology; Infrared analysis; Infrared spectroscopy; Kidneys; Liver; Magnetic resonance spectroscopy; Male; Mice; Mice, Inbred BALB C; Muscles; Nitric Oxide - metabolism; NMR spectroscopy; Pain; Pain perception; Palladium; Palladium - adverse effects; Palladium - pharmacology; Pretreatment; Serotonin; Side effects; Stomach; Thiocarbamates - adverse effects; Thiocarbamates - chemical synthesis; Thiocarbamates - pharmacology; Viability
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s00210-019-01645-y

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-κ S,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.