Department of Pharmacology, Faculty of Medicine, Benha University, Benha, 13511, Egypt.
Department of Clinical Laboratory Sciences, Turabah University College, Taif University, P.O. Box 11099, 21944, Taif, Saudi Arabia.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Oct;397(10):7623-7637. doi: 10.1007/s00210-024-03089-5. Epub 2024 Apr 30.
Tilmicosin (TIL) is a semisynthetic macrolide antibiotic with a broad spectrum of activity derived from tylosin. TIL is effective in the treatment of bovine and ovine respiratory diseases caused by different microbes. In parallel, Rhodiola rosea (RHO) is a popular herbal remedy because of its anti-inflammatory and antioxidant qualities. The experiment lasted for 12 days. Depending on the experimental group, the animals received either distilled water or RHO root extract dissolved in distilled water for 12 days through a stomach tube, and the single subcutaneous injection on day 6 of the experiment of either 500 μL of 0.9% NaCl or TIL dissolved in 500 μL 0.9% NaCl. Samples and blood were collected for serum analysis, gene expression, and immunohistochemistry screening at liver and kidney levels. TIL injection increased serum levels of hepatic and renal markers (ALP, ALT, AST, TC, TG, creatinine, and urea) with decreased total proteins. In parallel, TIL induced hepatic and renal oxidative stress as there was an increase in malondialdehyde levels, with a decrease in catalase and reduced glutathione activities. Of interest, pre-administration of RHO inhibited TIL-induced increase in hepato-renal markers, decreased oxidative stress, and increased liver and kidney antioxidant activities. Quantitative RT-PCR showed that TIL increased the liver's HSP70 (heat shock protein), NFkB, and TNF-α mRNA expression. Moreover, TIL upregulated the expression of desmin, nestin, and vimentin expression in the kidney. The upregulated genes were decreased significantly in the protective group that received RHO. Serum inflammatory cytokines and genes of inflammatory markers were affected in liver tissues (HSP70, NFkB, and TNF-α) and kidney tissues (desmin, nestin, and vimentin)-TIL-induced hepatic vacuolation and congestion together with glomerular atrophy. The immunoreactivity of PCNA and HMGB1 was examined immunohistochemically. At cellular levels, PCNA was decreased while HMGB1 immunoreactivity was increased in TIL-injected rats, which was improved by pre-administration of RHO. RHO administration protected the altered changes in liver and renal histology. Current findings support the possible use of RHO to shield the liver and kidney from the negative effects of tilmicosin.
替米考星（TIL）是一种半合成大环内酯类抗生素，具有广谱活性，源自泰乐菌素。TIL 可有效治疗由不同微生物引起的牛和羊呼吸道疾病。同时，红景天（RHO）因其具有抗炎和抗氧化特性而成为一种流行的草药疗法。实验持续了 12 天。根据实验组的不同，动物通过胃管连续 12 天分别给予蒸馏水或 RHO 根提取物溶解于蒸馏水中，并且在实验第 6 天通过皮下注射 500μL 0.9%NaCl 或溶解于 500μL 0.9%NaCl 中的 TIL。收集样本和血液，用于血清分析、基因表达和肝、肾水平的免疫组织化学筛选。TIL 注射增加了肝、肾标志物（碱性磷酸酶、丙氨酸转氨酶、天冬氨酸转氨酶、总胆固醇、甘油三酯、肌酐和尿素）的血清水平，同时总蛋白降低。同时，TIL 诱导肝、肾氧化应激，丙二醛水平升高，过氧化氢酶和还原型谷胱甘肽活性降低。有趣的是，RHO 的预先给药抑制了 TIL 引起的肝、肾标志物增加，降低了氧化应激，增加了肝、肾的抗氧化活性。实时定量 RT-PCR 显示 TIL 增加了肝脏的 HSP70（热休克蛋白）、NFkB 和 TNF-αmRNA 表达。此外，TIL 上调了肾脏中波形蛋白、巢蛋白和角蛋白的表达。在接受 RHO 保护的组中，这些上调的基因显著减少。血清炎症细胞因子和炎症标志物基因在肝组织（HSP70、NFkB 和 TNF-α）和肾组织（波形蛋白、巢蛋白和角蛋白）中受到影响-TIL 诱导的肝空泡化和淤血以及肾小球萎缩。通过免疫组织化学检查 PCNA 和 HMGB1 的免疫反应性。在细胞水平上，TIL 注射大鼠的 PCNA 减少，HMGB1 免疫反应性增加，而 RHO 的预先给药改善了这一情况。RHO 的给药保护了肝和肾组织学的改变。目前的研究结果支持红景天可能被用于保护肝脏和肾脏免受替米考星的负面影响。
