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金合欢乙酸乙酯提取物可预防顺铂诱导的成年雄性大鼠的 DNA 损伤、氧化应激和睾丸损伤。

Acacia hydaspica ethyl acetate extract protects against cisplatin-induced DNA damage, oxidative stress and testicular injuries in adult male rats.

机构信息

Department of Biochemistry, Quaid-i-Azam University, Islamabad, Pakistan.

Department of Animal Sciences, Quaid-i-Azam University, Islamabad, Pakistan.

出版信息

BMC Cancer. 2017 Dec 21;17(1):883. doi: 10.1186/s12885-017-3898-9.

DOI:10.1186/s12885-017-3898-9
PMID:29268699
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5740854/
Abstract

BACKGROUND

Cisplatin (CP), an effective anticancer agent, carries the risk of impairing testicular function leading to infertility. The present study aimed at evaluating the protective effect of A. hydaspica ethyl acetate extract (AHE) against CP-induced oxidative stress and testicular injuries in rats.

METHODS

Rats were divided into six groups (n = 6). Group I (control), group II (CP single dose on day 16). Group III received AHE for 21 days. Group IV (CP + AHE; post- treatment group). Group V (AHE + CP; pre-treatment group) and group VI (CP + Sily).

RESULTS

CP treatment reduced serum testosterone (T), LH and FSH, decreased the activity level of antioxidant enzymes while increased the concentration of oxidative stress markers, i.e. thiobarbituric acid reactive substances (TBARS), HO and nitric oxide (NO) along with corresponding DNA damages. Furthermore, CP induced adverse morphological changes in testis of rats including reduced epithelial height and tubular diameter, increased luminal diameter with impaired spermatogenesis. Pre and post-treatment with AHE reduced the side effects of CP in testis tissues through improvement in the reproductive hormonal secretions, enzymatic activities, histological and DNA damage parameters. Pretreatment seems to be more effective and equivalent to silymarin group in reversing the CP deleterious effects as compared to post-treatment.

CONCLUSION

The results demonstrated that A. hydaspica treatment in CP-induced testicular toxicity augments the antioxidants defense mechanism, reverted the level of fertility hormones, suppressed the histomorphological alterations and DNA damages and thus provides the evidence that it may have a therapeutic role in free radical mediated diseases.

摘要

背景

顺铂(CP)是一种有效的抗癌药物,但有损害睾丸功能导致不育的风险。本研究旨在评估 A. hydaspica 乙酸乙酯提取物(AHE)对 CP 诱导的大鼠氧化应激和睾丸损伤的保护作用。

方法

将大鼠分为六组(n=6)。第 I 组(对照组),第 II 组(第 16 天单次 CP 处理),第 III 组连续 21 天接受 AHE 处理,第 IV 组(CP+AHE;后处理组),第 V 组(AHE+CP;预处理组)和第 VI 组(CP+Sily)。

结果

CP 处理降低了血清睾酮(T)、LH 和 FSH 水平,降低了抗氧化酶的活性水平,同时增加了氧化应激标志物,即硫代巴比妥酸反应物质(TBARS)、HO 和一氧化氮(NO)的浓度,以及相应的 DNA 损伤。此外,CP 诱导大鼠睾丸组织出现形态学变化,包括上皮高度和管状直径降低,管腔直径增大,精子发生受损。AHE 预处理和后处理均可通过改善生殖激素分泌、酶活性、组织学和 DNA 损伤参数,减轻 CP 对睾丸组织的副作用。与后处理相比,预处理似乎更有效,与水飞蓟宾组相当,可逆转 CP 的有害影响。

结论

研究结果表明,A. hydaspica 处理 CP 诱导的睾丸毒性可增强抗氧化防御机制,恢复生育激素水平,抑制组织形态学改变和 DNA 损伤,从而为其在自由基介导的疾病中可能具有治疗作用提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b40e/5740854/356778f50575/12885_2017_3898_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b40e/5740854/0353ba4ca454/12885_2017_3898_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b40e/5740854/0c53cf819764/12885_2017_3898_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b40e/5740854/d74e1368a443/12885_2017_3898_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b40e/5740854/2fda2dc5f488/12885_2017_3898_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b40e/5740854/c3df678ae850/12885_2017_3898_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b40e/5740854/356778f50575/12885_2017_3898_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b40e/5740854/0353ba4ca454/12885_2017_3898_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b40e/5740854/0c53cf819764/12885_2017_3898_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b40e/5740854/d74e1368a443/12885_2017_3898_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b40e/5740854/2fda2dc5f488/12885_2017_3898_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b40e/5740854/c3df678ae850/12885_2017_3898_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b40e/5740854/356778f50575/12885_2017_3898_Fig6_HTML.jpg

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