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Influence of Pinealectomy and Long-term Melatonin Administration on Inflammation and Oxidative Stress in Experimental Gouty Arthritis

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Abstract

Gout is an inflammatory arthritis characterized by the deposition of monosodium urate (MSU) crystals in the joints or soft tissue. MSU crystals are potent inflammation inducers. Melatonin (MLT) is a powerful endogenous anti-inflammatory agent and effective in reducing cellular damage. In the present study, possible underlying mechanisms associated with anti-inflammatory and antioxidative effects were investigated in rats with gouty arthritis and melatonin deprivation treated with MLT. Fifty-six rats were divided into seven groups: control, sham control, pinealectomy (PNX), MSU (on the 30th day, single-dose 20 mg/ml, intraperitoneal), MSU + MLT (10 mg/kg/day for 30 days, intraperitoneal), MSU + PINX and MSU + PINX + MLT. PNX procedure was performed on the first day of the study. As compared to the controls, the results showed that MSU administration caused significant increases in oxidative stress parameters (malondialdehyde and total oxidant status). Besides, significant decreases in antioxidant defense systems (glutathione, superoxide dismutase and total antioxidant status) were observed. A statistically significant increase was found in the mean histopathological damage score in the groups that received MSU injection. It was found that histopathological changes were significantly reduced in the MSU + MLT group given MLT. In our study, it was determined that many histopathological changes, as well as swelling and temperature increase in the joint, which are markers of inflammation, were significantly reduced with MLT supplementation. These results suggest that melatonin ameliorates MSU-induced gout in the rat through inhibition of oxidative stress and proinflammatory cytokine production.

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Data Availability

The data used to support the findings of this study are available from the corresponding author on reasonable request.

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Funding

The research was supported by Karabuk University Scientific Research Fund (TSA-2020–2346).

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Authors and Affiliations

  1. Department of Medical Biochemistry, Faculty of Medicine, Karabuk University, Karabuk, Turkey

    Arwa Fadil Haqi Ballur, Eyup Altinoz, Yasemin Bicer & Melike Karayakali

  2. Department of Histology and Embryology, Faculty of Medicine, Mugla Sıtkı Kocman University, Mugla, Turkey

    Gurkan Yigitturk, Melike Ozgul Onal & Hulya Elbe

  3. Department of Physiology, Faculty of Medicine, Karabuk University, Karabuk, Turkey

    Mehmet Demir

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  1. Arwa Fadil Haqi Ballur
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Contributions

Mehmet Demir performed experiments and drafted the manuscript. Eyup Altinoz performed experiments and analyzed data, and Arwa Fadil Haqi Ballur, Yasemin Bicer, Melike Karayakali collected samples and analyzed data. Gurkan Yigitturk, Melike Ozgul Onal, Hulya Elbe helped in histopathological examination.

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Correspondence to Mehmet Demir.

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The study was approved by the Experimental Animals Ethics Committee of Zonguldak Bulent Ecevit University, Faculty of Medicine (Protocol No: 2020–10-07/05).

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Ballur, A.F.H., Altinoz, E., Yigitturk, G. et al. Influence of Pinealectomy and Long-term Melatonin Administration on Inflammation and Oxidative Stress in Experimental Gouty Arthritis. Inflammation 45, 1332–1347 (2022). https://doi.org/10.1007/s10753-022-01623-2

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