Blood-Derived Exosomes With Anti-Inflammatory Properties As A New Minimally Invasive Intratesticular Therapy For Aflatoxin B1-Associated Chronic Testopathy

IF 0.2 Q4 MEDICINE, GENERAL & INTERNAL
Fatemeh Mansouri Torghabeh, Mona Keivan, Mandana Fakoor, Reza Dadfar, Mahsa Nazarzadeh, Amir Abdolmaleki
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引用次数: 0

Abstract

Rationale — Aflatoxin B1 (AB1) is a dangerous toxin causing severe poisoning and even death in human. Testopathy or even infertility is one of the adverse effects of AB1. Exosomes (Ex) with anti-inflammatory action are known as biological substances derived from body fluids. This experimental study aimed to investigate the possible therapeutic effects of blood-derived Ex on orchitis caused by chronic exposure to AB1. Methods — Male rats (n=18) were distributed among three groups: control, AB1 and AB1+Ex. Orchitis was induced with AB1 (45 μL/kg of rat weight) for 40 days (3 times a week). A day later, 10 IU Ex were injected intratesticularly. A week later, testicular tissue and blood serum were sampled. To confirm the therapeutic effects of Ex, inflammatory genes (TNF-α, IL-6 and IL-10), nitric oxide (NO), malondialdehyde (MDA), testosterone (Tes) and sperm quality were fully evaluated. In addition, H&E staining was used to investigate tissue changes, and immunohistochemical (IHC) assessment was employed to detect the inflammatory protein, galectin-3. The results were analyzed using SPSS (v.19). Results and Discussion — Our results confirmed that Ex therapy can significantly (p<0.05) increase normal morphology (25.01±2.23 in the AB1+Ex group vs. 10.1±0.9 in the AB1 group), number (76.12±6.7 in the AB1+Ex group vs. 27.8±3.2 in AB1 group), and vitality (53.4±6.12 in AB1+Ex vs. 41.9±4.6 in AB1) of sperm cells. Blood-derived Ex significantly (p<0.05) reduced the expression of inflammatory genes (6-fold change was observed in AB1+Ex vs. 17-fold in AB1 for TNF-α, 3-fold change was detected in AB1+Ex vs. 6-fold in AB1 for IL-6, and 2-fold change took place in AB1+Ex vs. 6-fold in AB1 for IL-10), NO (23.1±2.6 in AB1+Ex vs. 62.8±8 0.1 in AB1) and MDA (33.2±4.9 in AB1+Ex vs. 68.9±5.46 in AB1), and increased Tes level (7.1±0.5 in AB1+Ex vs. 1.14±0.3 in AB1) in AB1-affected rats. Histopathological evaluations revealed tissue regeneration after Ex injection. Also, the produced sperm cells were of high quality. Conclusion — Intratesticular injection of Ex from the blood can be considered as a novel anti-inflammatory therapy after AB1-induced orchitis.
具有抗炎特性的血源性外泌体作为黄曲霉毒素b1相关慢性睾丸病的一种新的微创睾丸内治疗方法
理由:黄曲霉毒素B1 (AB1)是一种危险的毒素,可引起人类严重中毒甚至死亡。睾丸功能障碍甚至不育是AB1的不良反应之一。具有抗炎作用的外泌体(Ex)是一种来源于体液的生物物质。本实验旨在探讨血源性Ex对慢性暴露于AB1所致睾丸炎可能的治疗作用。方法:雄性大鼠18只,随机分为对照组、AB1组和AB1+Ex组。用AB1 (45 μL/kg大鼠体重)诱导睾丸炎40 d(每周3次)。1 d后,腹腔内注射10 IU Ex。一周后,采集睾丸组织和血清样本。为了证实Ex的治疗效果,我们对炎症基因(TNF-α、IL-6和IL-10)、一氧化氮(NO)、丙二醛(MDA)、睾酮(Tes)和精子质量进行了全面评估。采用H&E染色观察组织变化,免疫组化(IHC)检测炎症蛋白半凝集素-3。使用SPSS (v.19)对结果进行分析。结果与讨论:我们的结果证实,Ex治疗能显著(p<0.05)提高精子细胞的正常形态(AB1+Ex组25.01±2.23比AB1组10.1±0.9)、数量(AB1+Ex组76.12±6.7比AB1组27.8±3.2)和活力(AB1+Ex组53.4±6.12比AB1组41.9±4.6)。血源性Ex显著(p<0.05)降低了炎症基因的表达(TNF-α在AB1+Ex中变化6倍,在AB1+Ex中变化17倍,在AB1+Ex中变化3倍,在AB1+Ex中变化6倍,在AB1+Ex中变化2倍,在AB1+Ex中变化6倍,在AB1+Ex中变化23.1±2.6倍,在AB1中变化62.8±80.1)和MDA (AB1+Ex中变化33.2±4.9倍,在AB1中变化68.9±5.46),并增加了Tes水平(AB1+Ex中变化7.1±0.5倍,在AB1中变化1.14±0.3)。组织病理学检查显示注射Ex后组织再生。此外,产生的精子质量也很高。结论-睾丸内注射血源性Ex可作为一种新的抗炎治疗方法。
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来源期刊
Russian Open Medical Journal
Russian Open Medical Journal MEDICINE, GENERAL & INTERNAL-
CiteScore
0.90
自引率
0.00%
发文量
39
期刊介绍: Russian Open Medical Journal (RusOMJ) (ISSN 2304-3415) is an international peer reviewed open access e-journal. The website is updated quarterly with the RusOMJ’s latest original research, clinical studies, case reports, reviews, news, and comment articles. This Journal devoted to all field of medicine. All the RusOMJ’s articles are published in full on www.romj.org with open access and no limits on word counts. Our mission is to lead the debate on health and to engage, inform, and stimulate doctors, researchers, and other health professionals in ways that will improve outcomes for patients. The RusOMJ team is based mainly in Saratov (Russia), although we also have editors elsewhere in Russian and in other countries.
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