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  3. Targeting the PANoptosome with 3,4-Methylenedioxy-β-Nitrostyrene, Reduces PANoptosis and Protects the Kidney against Renal İschemia-Reperfusion Injury

Targeting the PANoptosome with 3,4-Methylenedioxy-β-Nitrostyrene, Reduces PANoptosis and Protects the Kidney against Renal İschemia-Reperfusion Injury

  • J Invest Surg. 2022 Nov-Dec;35(11-12):1824-1835. doi: 10.1080/08941939.2022.2128117.
Erdal Uysal 1,  Mehmet Dokur 2,  Faruk Kucukdurmaz 3,  Serdar Altınay 4,  Sait Polat 5,  Kadir Batcıoglu 6,  Efe Sezgın 7,  Tuğçe Sapmaz Erçakallı 5,  Aslı Yaylalı 8,  Yakup Yılmaztekin 9,  Zafer Cetın 10,  İlker Saygılı 11,  Osman Barut 12,  Hatem Kazımoglu 3,  Gokturk Maralcan 1,  Suna Koc 13,  Turkan Guney 14,  Nadire Eser 15,  Mehmet Sökücü 16,  Sema Nur Dokur 17
Affiliations

Affiliations

  • 1 Department of General Surgery, Sanko University School of Medicine, Gaziantep, Turkey.
  • 2 Department of Emergency Medicine, Biruni University Faculty of Medicine, İstanbul, Turkey.
  • 3 Department of Urology, Sanko University School of Medicine, Gaziantep, Turkey.
  • 4 Deparment of Pathology, Bakırköy Dr Sadi Konuk Health Aplication and Research Center, University of Health Sciences, School of Medicine, İstanbul, Turkey.
  • 5 Department of Histology and Embryology, Çukurova University, Faculty of Medicine, Adana, Turkey.
  • 6 Department of Biochemistry Malatya, Inonu University Faculty of Pharmacy, Battalgazi, Turkey.
  • 7 Izmir Yuksek Teknoloji Enstitusu, Laboratory of Nutrigenomics and Epidemiology, Food Engineering, Izmir Institute of Technology, İzmir, Turkey.
  • 8 Faculty of Medicine, Department of Histology and Embryology and IVF Center, Kahramanmaraş Sütçü İmam University, Kahramanmaraş, Turkey.
  • 9 Faculty of Pharmacy Department of Biochemistry, Inonu University, Malatya, Turkey.
  • 10 Department of Medical Biology, Sanko University School of Medicine, Gaziantep, Turkey.
  • 11 Department of Biochemistry, Sanko University School of Medicine, Gaziantep, Turkey.
  • 12 Department of Urology, Kahramanmaras Sutcu Imam University Faculty of Medicine, Kahramanmaras, Turkey.
  • 13 Department of Anesthesiology and Reanimation, Biruni University Faculty of Medicine, Istanbul, Turkey.
  • 14 Department of Medical Biochemistry, Beykent University, Faculty of Medicine, Istanbul, Turkey.
  • 15 Department of Pharmacology, Kahramanmaraş Sütçü İmam University, Faculty of Medicine, Kahramanmaraş, Turkey.
  • 16 Department of Patology, Sanko University School of Medicine, Gaziantep, Turkey.
  • 17 Faculty of Medicine, Biruni University, Istanbul, Turkey.
PMID: 36170987 DOI: 10.1080/08941939.2022.2128117
Abstract

Objectives: The objectives of this study were a) to investigate the effect of targeting the PANoptosome with 3,4-methylenedioxy-β-nitrostyrene (MNS) on PANoptosis in the Renal ischemia-reperfussion (RIR) model b) to investigate the kidney protective effect of MNS toward RIR injury.

Methods: Thirty-two rats were divided into four groups randomly. The groups were assigned as Control, Sham, DMSO (dimethyl sulfoxide) and MNS groups. The rats in the MNS group were intraperitoneally given 20 mg/kg of MNS 30 minutes before reperfusion. 2% DMSO solvent that dissolves MNS were given to the rats in DMSO group. Left nephrectomy was performed on the rats under anesthesia at the 6th hour after reperfusion. Glutathione Peroxidase (GPx), malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and 8-Okso-2'-deoksiguanozin (8-OHdG) levels were measured. Immunohistochemical analysis, electron microscopic and histological examinations were carried out in the tissues.

Results: Total tubular injury score was lower in the MNS group (p < 0.001). Caspase-3, Gasdermin D and MLK (Mixed Lineage Kinase Domain Like Pseudokinase) expressions were considerably decreased in the MNS group (p < 0.001). Apoptotic index (AI) was found to be low in the MNS group (p < 0.001). CAT and SOD levels were higher in the MNS Group (p = 0.006, p = 0.0004, respectively). GPx, MDA, and 8-OH-dG levels were similar (p > 0.05) in all groups. MNS considerably improved the tissue structure, based on the electron microscopic analysis.

Conclusions: Our results suggested that MNS administrated before the reperfusion reduces Pyroptosis, Apoptosis and Necroptosis. These findings suggest that MNS significantly protects the kidney against RIR injury by reducing PANoptosis as a result of specific inhibition of NOD-like Receptor pyrin domain-containing 3 (NLRP 3), one of the PANoptosome proteins.

Keywords

3,4-methylenedioxy-β-nitrostyrene; PANoptosis; PANoptosome; ischemia; renal.

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