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.
Highlights
Acute and chronic pancreatitis rank within the most common causes for hospital admission among gastrointestinal disorders and represent a significant healthcare burden [1]
Experimental and clinical studies suggest a correlation of the oxidative burden and disease severity in acute pancreatitis [31, 32], which prompted numerous studies investigating the effect of antioxidants in acute and chronic pancreatitis [7]
Mitochondriatargeted antioxidants have been shown to exert antioxidative effects at nanomolar concentrations inside mitochondria [23] and we hypothesized that scavenging reactive oxygen species (ROS) at their mitochondrial origin would reduce tissue injury in acute and chronic pancreatitis
Summary
Acute and chronic pancreatitis rank within the most common causes for hospital admission among gastrointestinal disorders and represent a significant healthcare burden [1]. 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. We aimed to characterize the influence of SkQ1 on tissue injury and pain in acute and chronic pancreatitis. SkQ1 did not influence pain, serological, or histological parameters of tissue injury in acute 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). After SkQ1 treatment, tissue injury is not ameliorated in acute pancreatitis and increased in chronic pancreatitis. Further studies will need to elucidate the risks and benefits of mitochondria-targeted antioxidants as an analgesic
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