Dipartimento di Medicina Sperimentale, Sez. Fisiologia Umana e Funzioni Biologiche Integrate "F. Bottazzi", Università degli Studi della Campania "Luigi Vanvitelli", Napoli, NA, Italy.
Dipartimento di Biologia, Università di Napoli 'Federico II, Napoli, NA, Italy.
J Exp Zool A Ecol Integr Physiol. 2022 Aug;337(7):729-738. doi: 10.1002/jez.2609. Epub 2022 Jun 6.
Herein is reported, for the first time in the rat Harderian gland (HG), the counteractive action of melatonin (Mlt), a well-known antioxidant radical scavenger, on the increased oxidative stress damages induced by a pro-oxidant substance, cadmium (Cd), an environmental pollutant also considered as endocrine disruptor. HG, an infraorbital gland present in almost all terrestrial vertebrates, produces a lipid secretion to lubricate the eyeball, as well as porphyrin/Mlt as light transducers. Moreover, HG is an extra-gonadal source of steroid sex hormones. Via ex vivo experiments lasting for 24 h, we verified the increased lipid peroxidation in Cd-treated glands, producing morphological alteration of the glandular epithelium, as well as an increased porphyrins accumulation. Moreover, Cd also induced a decreased protein level of the steroidogenic enzymes steroidogenic acute regulatory (StAR) and 3βHSD, and an increased mast cell number. Results obtained with Mlt cotreatment demonstrated that it decreased the levels of Cd-induced oxidative damage, with reversal of all the observed modification. Furthermore, the TUNEL assay showed that the increased number of apoptotic cells in Cd-treated HG was counteracted by the contemporaneous Mlt administration. Results confirmed that Mlt treatment restored the levels of two autophagy markers, LC3 and p62, counteracting the autophagy Cd-induced. Interestingly, the positive effects of Mlt alone were highlighted by the decreased rate of lipid peroxidation as compared with the control, confirming its antioxidant action. Combined data further confirmed the antioxidant action of Mlt in counteracting the degeneration provoked by reactive oxygen species (ROS) in the rat HG, a tissue extremely susceptible to oxidative stress condition.
在此首次报道，褪黑素（Mlt），一种众所周知的抗氧化自由基清除剂，对环境污染物镉（Cd）诱导的大鼠哈德腺（HG）氧化应激损伤具有拮抗作用。Cd 被认为是一种内分泌干扰物，也是一种环境污染物。HG 是一种存在于几乎所有陆地脊椎动物中的眶下腺，它产生一种脂质分泌物来润滑眼球，并产生 porphyrin/Mlt 作为光传感器。此外，HG 是类固醇性激素的一种性腺外来源。通过持续 24 小时的离体实验，我们验证了 Cd 处理的腺体中脂质过氧化作用增加，导致腺体上皮形态改变以及卟啉积累增加。此外，Cd 还诱导类固醇生成急性调节蛋白（StAR）和 3βHSD 的蛋白水平降低，以及肥大细胞数量增加。用 Mlt 共同处理得到的结果表明，它降低了 Cd 诱导的氧化损伤水平，逆转了所有观察到的变化。此外，TUNEL 检测表明，Cd 处理的 HG 中凋亡细胞数量的增加被同时给予 Mlt 逆转。结果证实，Mlt 处理恢复了两种自噬标志物 LC3 和 p62 的水平，逆转了 Cd 诱导的自噬。有趣的是，与对照组相比，Mlt 单独处理降低了脂质过氧化率，这进一步证实了其抗氧化作用。综合数据进一步证实了 Mlt 在拮抗大鼠 HG 中活性氧（ROS）引起的退行性变方面的抗氧化作用，因为 HG 对氧化应激条件极为敏感。
