眼镜蛇科毒素引起的精子功能缺陷、雄性生殖器官的促凋亡和炎症活性：山柰酚的拮抗作用。

Echis ocellatus venom-induced sperm functional deficits, pro-apoptotic and inflammatory activities in male reproductive organs in rats: antagonistic role of kaempferol.

机构信息

Department of Animal and Environmental Biology, Osun State University, Osogbo, Nigeria.

Biochemistry Unit, Department of Chemical Sciences, Kings University, Ode-Omu, Nigeria.

出版信息

BMC Pharmacol Toxicol. 2024 Aug 9;25(1):46. doi: 10.1186/s40360-024-00776-0.

DOI:10.1186/s40360-024-00776-0

PMID:39123263

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11311923/

Abstract

BACKGROUND

Echis ocellatus envenoming is potentially toxic initiating clinical damages on male reproductive system. Kaempferol is a therapeutic agent with neutralizing potentials on snake venom toxins. This study investigated the antagonistic effect of kaempferol on E. ocellatus venom (EoV)-induced reproductive toxicities.

METHODS

Fifty adult male rats were sorted at random into five groups of ten rats for this study. The control rats were allotted to group 1, while rats in groups 2-5 were injected with 0.22 mg/kg bw (LD) of EoV intraperitoneally. Rats in group 2 were not treated while groups 3-5 rats were treated with serum antivenom (0.2 ml), and 4 and 8 mg/kg bw of kaempferol post envenoming, respectively.

RESULTS

EoV actuated reproductive toxicity, significantly decreased sperm parameters, and enhanced inflammatory, oxidative stress, and apoptotic biomarkers in reproductive organs of untreated envenomed rats. However, treatment with kaempferol alleviated the venom-induced reproductive disorders with a dose dependent effect. Kaempferol significantly increased the testicular weight, organo-somatic index, sperm parameters, and normalized the levels of serum luteinizing hormone, testosterone, and follicle stimulating hormone. Kaempferol ameliorated testicular and epididymal oxidative stress as evidenced by significant decrease in malondialdehyde (MDA) levels, enhancement of reduced glutathione (GSH) levels, superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities. The inflammatory biomarkers; nitric oxide (NO) levels and myeloperoxidase activity (MPO), and apoptotic biomarkers; caspase 3 and caspase 9 activities were substantially suppressed in the testis and epididymis of envenomed rats treated with kaempferol.

CONCLUSION

Results revealed kaempferol as a potential remedial agent against reproductive toxicity that could manifest post-viper envenoming.

摘要

背景

埃及眼镜蛇毒液（EoV）可能会对男性生殖系统造成潜在的毒性损伤。山奈酚是一种具有中和蛇毒毒素潜力的治疗剂。本研究旨在探讨山奈酚对 E. ocellatus 毒液（EoV）诱导的生殖毒性的拮抗作用。

方法

将 50 只成年雄性大鼠随机分为五组，每组 10 只。对照组大鼠分配到第 1 组，而第 2-5 组大鼠则腹腔内注射 0.22mg/kg bw（LD）的 EoV。第 2 组大鼠未进行治疗，而第 3-5 组大鼠在被蛇毒咬伤后分别用血清抗蛇毒血清（0.2ml）和 4 和 8mg/kg bw 的山奈酚进行治疗。

结果

EoV 导致生殖毒性，显著降低精子参数，并增加未治疗的中毒大鼠生殖器官的炎症、氧化应激和凋亡生物标志物。然而，山奈酚的治疗减轻了毒液引起的生殖障碍，具有剂量依赖性。山奈酚显著增加睾丸重量、器官比体重、精子参数，并使血清促黄体生成素、睾酮和卵泡刺激素水平正常化。山奈酚改善了睾丸和附睾的氧化应激，表现为丙二醛（MDA）水平显著降低，还原型谷胱甘肽（GSH）水平、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPX）活性增强。中毒大鼠睾丸和附睾中的炎症生物标志物（一氧化氮（NO）水平和髓过氧化物酶活性（MPO））和凋亡生物标志物（半胱氨酸天冬氨酸蛋白酶 3 和半胱氨酸天冬氨酸蛋白酶 9 活性）显著降低。