Department of Veterinary Pharmacology and Toxicology, College of Veterinary Science (CVSc), Rajendranagar, Hyderabad 500030, PVNRTVU, Telangana, India.
Department of Veterinary Pathology, College of Veterinary Science (CVSc), Rajendranagar, Hyderabad 500030, PVNRTVU, Telangana, India.
Int Immunopharmacol. 2022 Aug;109:108915. doi: 10.1016/j.intimp.2022.108915. Epub 2022 Jun 6.
Hinokitiol is a natural bio-active tropolone derivative with promising antioxidant and anti-inflammatory properties. This study was conducted to evaluate the ameliorative effects of hinokitiol against acute pancreatitis induced by cerulein. Mice were pre-treated with hinokitiol intraperitoneally for 7 days (50 and 100 mg/kg), and on the final day of study, cerulein (6 × 50 μg/kg) was injected every hour for six times. Six hours after the last dose of cerulein, blood was collected from the mice through retro-orbital plexus for biochemical analysis. After blood collection, mice were euthanized and the pancreas was harvested for studying effects on oxidative stress, pro-inflammatory cytokines, immunohistochemistry and histopathology of tissue sections. Hinokitiol treatment significantly reduced edema of the pancreas and reduced the plasma levels of lipase and amylase in mice with cerulein-induced acute pancreatitis. It also attenuated the oxidative and nitrosative stress related damage as evident from the reduced malondialdehyde (MDA) and nitrite levels, which were significantly increased in the mice with acute pancreatitis. Furthermore, hinokitiol administration significantly reduced the pancreatitis-evoked decrease in the activity of catalase, glutathione (GSH) and superoxide dismutase (SOD) in the pancreatic tissue. Pre-treatment with hinokitiol significantly reduced the elevated levels of pro-inflammatory cytokines like interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α) as well as increased the levels of anti-inflammatory cytokine interleukin-10 (IL-10) in the pancreatic tissue of mice with acute pancreatitis. The immunohistochemical expression of nuclear factor kappa light chain enhancer of activated B cells (NF-κB), cyclooxygenase (COX-2) and TNF-α were significantly decreased by hinokitiol in mice with cerulein-induced acute pancreatitis. In conclusion, the results of the present study demonstrate that hinokitiol has significant potential to prevent cerulein-induced acute pancreatitis.
桧木醇是一种天然生物活性的三羟酮衍生物，具有有前景的抗氧化和抗炎特性。本研究旨在评估桧木醇对由 cerulein 诱导的急性胰腺炎的改善作用。小鼠经腹腔内预先用桧木醇处理 7 天（50 和 100mg/kg），在研究的最后一天，每隔 1 小时给 cerulein（6×50μg/kg）注射 6 次。在最后一次 cerulein 给药后 6 小时，通过眼眶后丛从小鼠中采集血液进行生化分析。采集血液后，处死小鼠并采集胰腺以研究对氧化应激、促炎细胞因子、免疫组织化学和组织切片的组织病理学的影响。桧木醇治疗可显著减轻胰腺水肿，并降低 cerulein 诱导的急性胰腺炎小鼠的血浆脂肪酶和淀粉酶水平。它还减轻了氧化和硝化应激相关损伤，这表现在丙二醛（MDA）和亚硝酸盐水平的降低，在急性胰腺炎小鼠中这些水平显著升高。此外，桧木醇给药可显著降低胰腺炎引起的胰腺组织中过氧化氢酶、谷胱甘肽（GSH）和超氧化物歧化酶（SOD）活性的降低。预先用桧木醇处理可显著降低急性胰腺炎小鼠中促炎细胞因子如白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）的升高水平，并增加抗炎细胞因子白细胞介素-10（IL-10）的水平。在 cerulein 诱导的急性胰腺炎小鼠中，桧木醇可显著降低核因子 kappa 轻链增强子的活化 B 细胞（NF-κB）、环氧化酶（COX-2）和 TNF-α的免疫组织化学表达。总之，本研究的结果表明桧木醇具有预防 cerulein 诱导的急性胰腺炎的显著潜力。
