EFFECT OF ACETYL L-CARNITINE ADMINISTRATION ON TESTICULAR HISTOPATHOLOGY, APOPTOSIS, AND OXIDATIVE STRESS IN AN EXPERIMENTAL CHRONIC ALCOHOLISM MODEL

IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Reproductive biomedicine online Pub Date : 2024-11-01 Epub Date: 2024-12-04 DOI:10.1016/j.rbmo.2024.104540
Merve Gorgulu , Gizem Gamze Tas , Gamze Zengin , Hakan Er , Sevim Ercan Kelek , Leyla Sati
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Abstract

Objective

Alcohol addiction is recognized as a serious public health issue today. The World Health Organization classifies alcohol as substances that cause both physiological and psychological dependence when consumed over prolonged periods. Studies clearly indicate that chronic alcohol consumption has detrimental effects on the male reproductive system, suggesting that it is a risk factor for male fertility with reproductive and endocrine problems. Acetaldehyde, which is formed by the metabolism of alcohol, causes the production of free radicals when oxidized, which triggers apoptotic processes and oxidative stress. It is known that chronic alcohol use results in oxidative stress. However, various studies have shown that acetyl-L-carnitine (ALCAR) has antioxidant effects on several biological mechanisms under different conditions. Therefore, we aimed to investigate the potential effects of ALCAR administration on sperm motility, testicular histopathology, apoptosis, and oxidative stress in rats chronically exposed to ethanol (EtOH).

Materials and Methods

Rats were randomly separated into 4 groups. Over the course of the 4-week period, EtOH (5 g/kg, 25% w/v), ALCAR (50 mg/kg), and EtOH (5 g/kg, 25% w/v) + ALCAR (50 mg/kg) were given to rats by oral gavage daily (n=10/group). However, the control group received only distilled water. Epididymal sperm motility and testicular weight index were measured in line with testicular histopathology and modified Johnsen scoring. TUNEL assay was used for the assessment of the apoptotic index. Total oxidants and antioxidant status were analyzed with ELISA.

Results

Sperm motility and testicular modified Johnsen scores were decreased in the EtOH group (p<0.001). However, the EtOH+ALCAR group showed similar levels as to the control group. Even though no significant difference was determined for testicular weight index, immature germ cells spilled into the lumen, vacuolization in the intertubular area, and expansion in the interstitial area were observed in the EtOH group in contrast to normal testicular histology in the EtOH+ALCAR group. Chronic alcohol administration caused a significant increase in the apoptotic index (p<0.05) and oxidative stress (p<0.001). Nevertheless, we detected decreased apoptotic index and oxidative stress levels in the EtOH+ALCAR group compared to the EtOH group.

Conclusion

Our results indicate that ALCAR, an antioxidant compound, may have beneficial effects against the damages caused by chronic use of alcohol, such as poor sperm motility, testicular atrophy, and increased oxidative stress. However, the exact efficacy of ALCAR on the treatment for male infertility and metabolic consequences of chronic alcohol consumption needs to be confirmed by further investigations.
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乙酰左旋肉碱对实验性慢性酒精中毒模型睾丸组织病理学、细胞凋亡和氧化应激的影响
酒精成瘾是当今公认的一个严重的公共健康问题。世界卫生组织将酒精归类为长时间饮用会导致生理和心理依赖的物质。研究清楚地表明,长期饮酒对男性生殖系统有不利影响,这表明它是男性生育能力与生殖和内分泌问题的一个危险因素。由酒精代谢形成的乙醛在氧化时产生自由基,从而引发细胞凋亡过程和氧化应激。众所周知,长期饮酒会导致氧化应激。然而,各种研究表明,乙酰左旋肉碱(ALCAR)在不同条件下具有多种生物机制的抗氧化作用。因此,我们旨在研究ALCAR给药对长期暴露于乙醇(EtOH)的大鼠精子活力、睾丸组织病理学、细胞凋亡和氧化应激的潜在影响。材料与方法将大鼠随机分为4组。4周内,大鼠每天灌胃EtOH (5 g/kg, 25% w/v)、ALCAR (50 mg/kg)和EtOH (5 g/kg, 25% w/v) + ALCAR (50 mg/kg) (n=10/组)。然而,对照组只喝蒸馏水。根据睾丸组织病理学和改良Johnsen评分,测量附睾精子活力和睾丸体重指数。TUNEL法测定细胞凋亡指数。ELISA法分析总氧化剂和抗氧化状态。结果EtOH组精子活力和睾丸改良Johnsen评分降低(p<0.001)。然而,EtOH+ALCAR组显示与对照组相似的水平。尽管睾丸重量指数没有明显差异,但与EtOH+ALCAR组的正常睾丸组织学相比,EtOH组观察到未成熟生殖细胞溢入管腔,管间区空泡化,间质区扩张。慢性酒精给药导致细胞凋亡指数(p<0.05)和氧化应激(p<0.001)显著升高。然而,我们检测到与EtOH组相比,EtOH+ALCAR组的凋亡指数和氧化应激水平降低。结论ALCAR是一种抗氧化化合物,对长期饮酒引起的精子运动能力差、睾丸萎缩、氧化应激增加等损伤有一定的保护作用。然而,ALCAR治疗男性不育症和慢性饮酒代谢后果的确切疗效需要进一步的研究来证实。
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来源期刊
Reproductive biomedicine online
Reproductive biomedicine online 医学-妇产科学
CiteScore
7.20
自引率
7.50%
发文量
391
审稿时长
50 days
期刊介绍: Reproductive BioMedicine Online covers the formation, growth and differentiation of the human embryo. It is intended to bring to public attention new research on biological and clinical research on human reproduction and the human embryo including relevant studies on animals. It is published by a group of scientists and clinicians working in these fields of study. Its audience comprises researchers, clinicians, practitioners, academics and patients. Context: The period of human embryonic growth covered is between the formation of the primordial germ cells in the fetus until mid-pregnancy. High quality research on lower animals is included if it helps to clarify the human situation. Studies progressing to birth and later are published if they have a direct bearing on events in the earlier stages of pregnancy.
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