Bilgic Yilmaz, Akbulut Sami, Aksungur Zeynep, Erdemli Mehmet Erman, Ozhan Onural, Parlakpinar Hakan, Vardi Nigar, Turkoz Yusuf
Department of Gastroenterology, Inonu University Faculty of Medicine, Malatya 44280, Turkey.
Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya 44280, Turkey.
Exp Ther Med. 2018 Nov;16(5):4049-4057. doi: 10.3892/etm.2018.6683. Epub 2018 Sep 3.
The aim of the present study was to investigate the protective effect of dexpanthenol (Dexp) against cisplatin (Cis)-induced hepatotoxicity. Thirty-two Sprague Dawley rats were divided into four groups: Control group (n=8), Dexp group (n=8, 500 mg/kg/ip/daily single dose/3 days Dexp), Cis group (n=8, 7 mg/kg/ip/single dose Cis) and Cis+Dexp group (n=8, 500 mg/kg/ip/daily single dose/3 days Dexp +7 mg/kg/ip/single dose Cis). MDA, CAT, GSH, GSH-Px, TOS, TAS, OSI, Total Nitrit, IL-1β, IL-6 and TNF-α levels were analyzed in liver tissue samples. After paraffinization of liver tissue samples, histopathological (congestion, loss of glycogen, number of Kupffer cells) and immunohistochemical (caspase-3 expression) parameters were assessed on the paraffinized liver sections. GSH, TAS, TOS, OSI, Tot Nit, L-Arginine, ADMA and SDMA levels were measured in the serum samples. Statistically significant differences were found between the groups in terms of all liver tissue biochemical parameters, with the exception of IL-1β and TNF-α levels. GSH, CAT, GSH-Px, TAS and Tot Nit levels were significantly higher in the Cis+Dexp group compared to the Cis group, whereas MDA, TOS, OSI and IL-6 levels were higher in the Cis group. Similarly, serum GSH, TAS, Tot Nit levels were higher in the Cis+Dexp group whereas TOS, L-Arginine, ADMA and SDMA levels were higher in Cis group. There were statistically significant differences between Control and Cis groups in terms of congestion increase, increase of glycogen loss, increase of Kupffer cell number and increase of caspase-3 expression (P<0.001). There was a statistically significant difference between the Cis and the Cis+Dexp groups in terms of histopathologic parameters, with the exception of congestion (P<0.001). To conclude, histopathological, immunohistochemical, and biochemical results of this study demonstrated that Dexp has a protective effect against Cis-induced hepatotoxicity.
本研究的目的是探讨右泛醇（Dexp）对顺铂（Cis）诱导的肝毒性的保护作用。将32只Sprague Dawley大鼠分为四组：对照组（n = 8）、Dexp组（n = 8，500 mg/kg/腹腔注射/每日单次剂量/3天Dexp）、Cis组（n = 8，7 mg/kg/腹腔注射/单次剂量Cis）和Cis+Dexp组（n = 8，500 mg/kg/腹腔注射/每日单次剂量/3天Dexp + 7 mg/kg/腹腔注射/单次剂量Cis）。分析肝组织样本中的丙二醛（MDA）、过氧化氢酶（CAT）、谷胱甘肽（GSH）、谷胱甘肽过氧化物酶（GSH-Px）、总氧化应激（TOS）、总抗氧化能力（TAS）、氧化应激指数（OSI）、总亚硝酸盐、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平。肝组织样本石蜡包埋后，对石蜡包埋的肝切片评估组织病理学（充血、糖原丧失、库普弗细胞数量）和免疫组织化学（半胱天冬酶-3表达）参数。检测血清样本中的GSH、TAS、TOS、OSI、总亚硝酸盐、L-精氨酸、不对称二甲基精氨酸（ADMA）和对称二甲基精氨酸（SDMA）水平。除IL-1β和TNF-α水平外，各肝组织生化参数在组间均存在统计学显著差异。与Cis组相比，Cis+Dexp组的GSH、CAT、GSH-Px、TAS和总亚硝酸盐水平显著更高，而Cis组的MDA、TOS、OSI和IL-6水平更高。同样，Cis+Dexp组的血清GSH、TAS、总亚硝酸盐水平更高，而Cis组的TOS、L-精氨酸、ADMA和SDMA水平更高。对照组和Cis组在充血增加、糖原丧失增加、库普弗细胞数量增加和半胱天冬酶-3表达增加方面存在统计学显著差异（P<0.001）。除充血外，Cis组和Cis+Dexp组在组织病理学参数方面存在统计学显著差异（P<0.001）。总之，本研究的组织病理学、免疫组织化学和生化结果表明，Dexp对Cis诱导的肝毒性具有保护作用。
