Effect of Oligopeptides-Homologues of the Fragment of ACTH15-18 on Morphogenetic Markers of Stress in the Adrenal Glands on the Model of Acute Cold Injury in Rats.

IF 1.8 Q3 PHARMACOLOGY & PHARMACY
Olesia Kudina, Sergii Shtrygol, Yulia Larjanovska
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Abstract

Objectives: Aim of the current study was to evaluate the stress-protective effect of oligopeptides-homologues of the adrenocorticotropic hormone (ACTH) fragment 15-18 on morphogenetic signs of stress reaction of the adrenal glands under acute cold exposure (CE) in rats.

Materials and methods: The acute cold stress was reproduced by placing random-bred male rats in a freezer at a temperature of -18°C for 2 hours. The peptides-homologous of ACTH15-18 acetyl-(D-Lys)-Lys-Arg-Arg-amide (KK-1) and acetyl-(D-Lys)-Lys-(D-Arg)-Arg-amide (KK-5) and the reference medicine (Sema) were administered intranasally in a dose of 20 mg/kg 30 minutes before and after CE. Rectal temperature was measured before and 10 min after CE. Zona glomeruloza, zona fasciculata, zona reticularis, and the area of cells and nuclei of adrenocorticocytes of the zona fasciculata were measured.

Results: KK-1 significantly prevented structural changes in the adrenal cortex and medulla and stabilized the secretory activity of glucocorticoid-producing cells. However, the congestion of the capillaries of the zona fasciculata and zona reticularis remained in some locations. Zona fasciculata cells had a marked tendency to decrease, and the area of nuclei significantly decreased (p<0.05) recovering the width to control animals' markers. KK-5 had a more marked recovery of the adrenal glands (a greater saturation of cytoplasm of adrenocorticocytes of zona glomerulosa and zona fasciculata). The number of chromaffin cells at rest was increased in the adrenal medulla. KK-5 statistically significantly normalized both the area of cells (p<0.05) and the area of nuclei (p<0.05) of the zona fasciculata, unlike KK-1, which reliably restored only the marker of the nuclei area. Some morphometric parameters of acute stress hypertrophy remained in the adrenal glands of rats receiving Sema.

Conclusion: KK-1 and KK-5 prevented the manifestation of acute stress reactions in the adrenal cortex of rats. KK-5 had a more marked stress-protective effect compared with the peptide KK-1. Both study substances exceeded the reference medicine Sema. KK-5 is a promising stres-sprotector and frigoprotector.

ACTH15-18片段寡肽同源物对急性冷损伤大鼠肾上腺应激形态发生标志物的影响
目的:探讨促肾上腺皮质激素(ACTH)片段15-18寡肽同源物对大鼠急性冷暴露(CE)应激反应形态发生的保护作用。材料与方法:将随机繁殖的雄性大鼠置于-18℃的冷冻室中2小时,再现急性冷应激。将ACTH15-18乙酰基-(D-Lys)-赖氨酸-精氨酸酰胺(KK-1)、乙酰基-(D-Lys)-赖氨酸-(D-Arg)-精氨酸酰胺(KK-5)和参比药物(Sema)的同源肽分别在CE前后30分钟以20 mg/kg的剂量经鼻给药。在CE前和CE后10 min分别测量直肠温度。测定肾小球带、束状带、网状带及束状带肾上腺皮质细胞的细胞面积和细胞核面积。结果:KK-1能显著阻止肾上腺皮质和髓质结构改变,稳定糖皮质激素生成细胞的分泌活性。然而,束状带和网状带的毛细血管充血在一些地方仍然存在。束状带细胞有明显减少的趋势,细胞核面积明显减小(肾小球带和束状带)。肾上腺髓质中处于静止状态的嗜铬细胞数量增加。KK-5与KK-1不同,KK-5使束状带的细胞面积归一化,而KK-1只可靠地恢复了细胞核面积的标记。注射Sema的大鼠肾上腺仍保留了一些急性应激性肥大的形态学参数。结论:KK-1和KK-5抑制大鼠肾上腺皮质急性应激反应的发生。与肽KK-1相比,KK-5具有更显著的应激保护作用。两种研究物质均超过参比药物Sema。KK-5是一种很有前途的压力保护剂和低温保护剂。
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来源期刊
CiteScore
3.60
自引率
5.90%
发文量
79
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