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The Analgesic Effect of the Mitochondria-Targeted Antioxidant SkQ1 in Pancreatic Inflammation.

Abstract

Background.

Chronic pancreatitis is one of the main risk factors for pancreatic cancer. In acute and chronic pancreatitis, oxidative stress is thought to play a key role. In this respect, the recently described mitochondria-targeted antioxidant SkQ1 effectively scavenges reactive oxygen species at nanomolar concentrations. Therefore, we aimed to characterize the influence of SkQ1 on tissue injury and pain in acute and chronic pancreatitis. Methods. Both acute and chronic pancreatitis were induced in C57BL/6 mice by intraperitoneal cerulein injections and treatment with SkQ1 was carried out by peroral applications. Hyperalgesia was assessed by behavioral observation and measurement of abdominal mechanical sensitivity. Blood serum and pancreatic tissue were harvested for analysis of lipase and histology.

Results.

SkQ1 did not influence pain, serological, or histological parameters of tissue injury in acute pancreatitis. In chronic pancreatitis, a highly significant reduction of pain-related behavior (p < 0.0001) was evident, but histological grading revealed increased tissue injury in SkQ1-treated animals (p = 0.03).

Conclusion.

After SkQ1 treatment, tissue injury is not ameliorated in acute pancreatitis and increased in chronic pancreatitis. However, we show an analgesic effect in chronic pancreatitis. Further studies will need to elucidate the risks and benefits of mitochondria-targeted antioxidants as an analgesic.

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  • Authors+Show Affiliations

    ,

    Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Ludwig Maximilians University, Campus Grosshadern, 81377 Munich, Germany.

    ,

    Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Ludwig Maximilians University, Campus Grosshadern, 81377 Munich, Germany.

    ,

    Institute of Pathology, Ludwig Maximilians University, 81377 Munich, Germany.

    ,

    Institute of Laboratory Medicine, Ludwig Maximilians University, 81377 Munich, Germany.

    ,

    Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Ludwig Maximilians University, Campus Grosshadern, 81377 Munich, Germany.

    ,

    Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Ludwig Maximilians University, Campus Grosshadern, 81377 Munich, Germany.

    ,

    Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Ludwig Maximilians University, Campus Grosshadern, 81377 Munich, Germany.

    ,

    Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Ludwig Maximilians University, Campus Grosshadern, 81377 Munich, Germany.

    ,

    Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Ludwig Maximilians University, Campus Grosshadern, 81377 Munich, Germany.

    Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Ludwig Maximilians University, Campus Grosshadern, 81377 Munich, Germany.

    Source

    MeSH

    Acute Disease
    Analgesics
    Animals
    Antioxidants
    Behavior, Animal
    Biomarkers
    Ceruletide
    Disease Models, Animal
    Female
    Hyperalgesia
    Lipase
    Mice, Inbred C57BL
    Mitochondria
    Motor Activity
    Pain Perception
    Pancreas
    Pancreatitis
    Pancreatitis, Chronic
    Plastoquinone
    Risk Factors

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    27274778

    Citation

    Weniger, Maximilian, et al. "The Analgesic Effect of the Mitochondria-Targeted Antioxidant SkQ1 in Pancreatic Inflammation." Oxidative Medicine and Cellular Longevity, vol. 2016, 2016, p. 4650489.
    Weniger M, Reinelt L, Neumann J, et al. The Analgesic Effect of the Mitochondria-Targeted Antioxidant SkQ1 in Pancreatic Inflammation. Oxid Med Cell Longev. 2016;2016:4650489.
    Weniger, M., Reinelt, L., Neumann, J., Holdt, L., Ilmer, M., Renz, B., ... D'Haese, J. G. (2016). The Analgesic Effect of the Mitochondria-Targeted Antioxidant SkQ1 in Pancreatic Inflammation. Oxidative Medicine and Cellular Longevity, 2016, p. 4650489. doi:10.1155/2016/4650489.
    Weniger M, et al. The Analgesic Effect of the Mitochondria-Targeted Antioxidant SkQ1 in Pancreatic Inflammation. Oxid Med Cell Longev. 2016;2016:4650489. PubMed PMID: 27274778.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - The Analgesic Effect of the Mitochondria-Targeted Antioxidant SkQ1 in Pancreatic Inflammation. AU - Weniger,Maximilian, AU - Reinelt,Leonard, AU - Neumann,Jens, AU - Holdt,Lesca, AU - Ilmer,Matthias, AU - Renz,Bernhard, AU - Hartwig,Werner, AU - Werner,Jens, AU - Bazhin,Alexandr V, AU - D'Haese,Jan G, Y1 - 2016/05/04/ PY - 2016/01/25/received PY - 2016/04/07/accepted PY - 2016/6/9/entrez PY - 2016/6/9/pubmed PY - 2017/3/14/medline SP - 4650489 EP - 4650489 JF - Oxidative medicine and cellular longevity JO - Oxid Med Cell Longev VL - 2016 N2 - Background. Chronic pancreatitis is one of the main risk factors for pancreatic cancer. In acute and chronic pancreatitis, oxidative stress is thought to play a key role. In this respect, the recently described mitochondria-targeted antioxidant SkQ1 effectively scavenges reactive oxygen species at nanomolar concentrations. Therefore, we aimed to characterize the influence of SkQ1 on tissue injury and pain in acute and chronic pancreatitis. Methods. Both acute and chronic pancreatitis were induced in C57BL/6 mice by intraperitoneal cerulein injections and treatment with SkQ1 was carried out by peroral applications. Hyperalgesia was assessed by behavioral observation and measurement of abdominal mechanical sensitivity. Blood serum and pancreatic tissue were harvested for analysis of lipase and histology. Results. SkQ1 did not influence pain, serological, or histological parameters of tissue injury in acute pancreatitis. In chronic pancreatitis, a highly significant reduction of pain-related behavior (p < 0.0001) was evident, but histological grading revealed increased tissue injury in SkQ1-treated animals (p = 0.03). Conclusion. After SkQ1 treatment, tissue injury is not ameliorated in acute pancreatitis and increased in chronic pancreatitis. However, we show an analgesic effect in chronic pancreatitis. Further studies will need to elucidate the risks and benefits of mitochondria-targeted antioxidants as an analgesic. SN - 1942-0994 UR - https://wwww.unboundmedicine.com/medline/citation/27274778/The_Analgesic_Effect_of_the_Mitochondria_Targeted_Antioxidant_SkQ1_in_Pancreatic_Inflammation L2 - https://dx.doi.org/10.1155/2016/4650489 DB - PRIME DP - Unbound Medicine ER -