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改善一线抗结核药物(利福平+异烟肼+吡嗪酰胺)联合使用对正常Wistar大鼠诱导的睾丸毒性。

Ameliorates Testicular Toxicity Induced by Combination of First-Line Tuberculosis Drugs (Rifampicin + Isoniazid + Pyrazinamide) in Normal Wistar Rats.

作者信息

Sharma Radhika, Goyal Neha, Singla Mandakini, Sharma Vijay Lakshmi

机构信息

a Department of Zoology , Panjab University , Chandigarh , India.

b Department of Zoology , School of Basic and Applied Sciences, Maharaja Agrasen University , Baddi , India.

出版信息

J Diet Suppl. 2019;16(4):417-430. doi: 10.1080/19390211.2018.1470127. Epub 2018 Jun 28.

DOI:10.1080/19390211.2018.1470127
PMID:29953299
Abstract

First-line antituberculosis drugs, namely, isoniazid (INH), rifampicin (RIF), and pyrazinamide (PZA), contribute to diverse pathological complications. Testicular toxicity is one such complication. DC is an herb with potentially curative characteristics. The aim of this study was to test whether extract of DC (Berberidaceae) has curing potential against testicular toxicity. Characterization of extract was done using ultra-performance liquid chromatography along with acute toxicity testing. Antioxidant activity of extract was checked by DPPH inhibition assay and HO scavenging assay. Rats were dosed once daily for 28 days in groups: control group (saline), toxicant group (30.85 mg/kg body weight INH + 61.7 mg/kg body weight RIF + 132.65 mg/kg body weight PZA), treatment groups (TB drugs + 150/300 mg/kg body weight extract) and standard group (TB drugs +100 mg/kg body weight silymarin). Spectrophotometric evaluations of lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione-S-transferase (GST), and catalase (CAT) content in testes were done using standard protocols. DNA fragmentation and histopathological studies were performed to check the damage at the cellular level. Acute toxicity studies revealed LD > 5 g/Kg body weight of extract. IC for DPPH free-radical scavenging activity and HO scavenging assay were 44.78 µg/mL and 85.28 µg/mL, respectively. Results revealed significant increase in thiobarbituric acid reactive substances, decrease in glutathione and different antioxidants levels, DNA fragmentation pattern, and changes in histology in toxicant group. All the changes were absent in high-dose (300 mg/kg body weight) extract treatment group. This work proved that extract has protective efficacy against testicular damage caused by anti-TB drugs.

摘要

一线抗结核药物,即异烟肼(INH)、利福平(RIF)和吡嗪酰胺(PZA),会导致多种病理并发症。睾丸毒性就是其中一种并发症。黄连是一种具有潜在治疗特性的草药。本研究的目的是测试黄连(小檗科)提取物是否具有治疗睾丸毒性的潜力。提取物的表征采用超高效液相色谱法并进行急性毒性测试。通过DPPH抑制试验和羟基自由基清除试验检测提取物的抗氧化活性。将大鼠分为几组,每天给药一次,持续28天:对照组(生理盐水)、毒物组(30.85毫克/千克体重异烟肼 + 61.7毫克/千克体重利福平 + 132.65毫克/千克体重吡嗪酰胺)、治疗组(抗结核药物 + 150/300毫克/千克体重提取物)和标准组(抗结核药物 + 100毫克/千克体重水飞蓟宾)。使用标准方案对睾丸中的脂质过氧化(LPO)、还原型谷胱甘肽(GSH)、超氧化物歧化酶(SOD)、谷胱甘肽 - S - 转移酶(GST)和过氧化氢酶(CAT)含量进行分光光度评估。进行DNA片段化和组织病理学研究以检查细胞水平的损伤。急性毒性研究表明提取物的半数致死量>5克/千克体重。DPPH自由基清除活性和羟基自由基清除试验的半数抑制浓度分别为44.78微克/毫升和85.28微克/毫升。结果显示,毒物组中硫代巴比妥酸反应性物质显著增加、谷胱甘肽和不同抗氧化剂水平降低、DNA片段化模式以及组织学变化。高剂量(300毫克/千克体重)提取物治疗组中所有这些变化均不存在。这项工作证明黄连提取物对抗结核药物引起的睾丸损伤具有保护作用。

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