Histopathological Scoring of Renal Injury in an Experimental Model of Acute Pancreatitis Caused by Karwinskia humboldtiana Fruit: Exploring Its Potential Utility in the Treatment of Pancreatic Cancer

利用卡尔文斯基果实诱发急性胰腺炎的实验模型进行肾损伤组织病理学评分:探索其在胰腺癌治疗中的潜在应用价值

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Abstract

Background: Karwinskia humboldtiana (Kh) is a toxic plant that produces a fruit that, when ingested in large quantities, causes damage to the lungs, liver, kidneys, pancreas, and duodenum. Pancreatic damage was measured using a semiquantitative score, revealing that it is progressive and characterized by selective apoptosis and necrosis of the exocrine portion. However, renal injury has not been evaluated using injury scales and has only been reported descriptively. Pancreatic adenocarcinoma is one of the top five causes of cancer death in the United States, and options for its treatment are limited. One of the toxins extracted from the fruit (T-514) has been tested as a possible antineoplastic agent in various cancer cell lines. In order to preliminarily assess its possible usefulness against pancreatic cancer, we decided to re-evaluate kidney damage using a semi-quantitative scale, hoping to obtain a lesser injury intensity than that reported in the pancreas. Methods: We analyzed kidney samples from the same model of acute pancreatitis by Kh by semiquantitative scoring to compare the results with those previously reported in the pancreas, and performed a TUNEL assay to analyze cell death in the kidney. Results: The renal injury that occurs in this model of Kh poisoning consists mainly of hydropic degeneration and loss of microvilli in proximal tubules. According to the scale used in this work, the following percentages of kidney injury were obtained: 8.26 ± 0.93% for the control group, 9.65 ± 1.60%, 11.04 ± 1.36%, 12.78 ± 2.46%, 14.03 ± 1.83% and 15.76 ± 3.73% for the groups 24 h, 48 h, 72 h, 96 h and 120 h after Kh administration. In contrast, the following were reported for the pancreas: 0.28 ± 0.83% for the control group, 14.81 ± 7.64%, 35.63 ± 12.05%, 67.13 ± 5.27%, 85.28 ± 13.14% and 87.13 ± 11.17% for the groups 24 h, 48 h, 72 h, 96 h and 120 h after Kh administration. These results indicate that pancreatic injury is 71.37% more intense than renal injury at 120 h after Kh. No evidence of nuclear chromatin fragmentation was found in the kidney. Conclusions: The renal damage in this model of acute pancreatitis is of lower intensity than the pancreatic damage, suggesting that Kh and its toxins may be useful in the treatment of pancreatic cancer and their study in an in vitro or in vivo cancer model is justified.

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