The Analgesic Effect of the Mitochondria-Targeted Antioxidant SkQ1 in Pancreatic Inflammation.
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.
Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Ludwig Maximilians University, Campus Grosshadern, 81377 Munich, Germany.
Maximilian
M
Weniger
Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Ludwig Maximilians University, Campus Grosshadern, 81377 Munich, Germany.
Leonard
L
Reinelt
Institute of Pathology, Ludwig Maximilians University, 81377 Munich, Germany.
Jens
J
Neumann
Institute of Laboratory Medicine, Ludwig Maximilians University, 81377 Munich, Germany.
Lesca
L
Holdt
Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Ludwig Maximilians University, Campus Grosshadern, 81377 Munich, Germany.
Matthias
M
Ilmer
Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Ludwig Maximilians University, Campus Grosshadern, 81377 Munich, Germany.
Bernhard
B
Renz
Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Ludwig Maximilians University, Campus Grosshadern, 81377 Munich, Germany.
Werner
W
Hartwig
Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Ludwig Maximilians University, Campus Grosshadern, 81377 Munich, Germany.
Jens
J
Werner
Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Ludwig Maximilians University, Campus Grosshadern, 81377 Munich, Germany.
Alexandr V
AV
Bazhin
Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Ludwig Maximilians University, Campus Grosshadern, 81377 Munich, Germany.
Jan G
JG
D'Haese
D000208:Acute Disease; D000700:Analgesics / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D002108:Ceruletide; D004195:Disease Models, Animal; D005260:Female; D006930:Hyperalgesia / Q000209:etiology / Q000517:prevention & control* / Q000523:psychology; D008049:Lipase / Q000097:blood; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D058748:Pain Perception / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D010971:Plastoquinone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D012307:Risk Factors
C532038:10-(6'-plastoquinonyl)decyltriphenylphosphonium; D000700:Analgesics; D000975:Antioxidants; D015415:Biomarkers; D002108:Ceruletide; D008049:Lipase; D010971:Plastoquinone