Mishra Ankit, Singh K P
Neurobiology Lab, Department of Zoology, University of Allahabad, Prayagraj, India.
Drug Chem Toxicol. 2022 Nov;45(6):2399-2410. doi: 10.1080/01480545.2021.1954698. Epub 2021 Aug 1.
The interaction between neuroendocrine and immune components of the gut maintains the organism's physical and psychological health. Its disruption may reflect in disease conditions such as inflammatory bowel disease (IBD) and mental illness. The lipopolysaccharide (LPS) disrupts the endocrine-immune homeostasis resulting in gut toxicity. The Neurotensin receptor-1 (NTR-1) agonist PD 149163 (PD) acts as an atypical antipsychotic drug in psychiatric illness, but its role in modulating gut pathophysiology remains unknown. Therefore, the aim of the present study was to evaluate the protective effect of PD against LPS-induced gut toxicity. Swiss albino female mice (12 weeks) were divided into six groups ( = 6/group): (I) Control, (II) LPS (1 mg/kg, for 5 days), (III) LPS (1 mg/kg, for 5 days)+PD low (100 µg/kg, for 21 days), (IV) LPS (1 mg/kg, for 5 days)+PD high (300 µg/kg, for 21 days), (V) PD low (100 µg/kg, for 21 days), and (VI) PD high (300 µg/kg, for 21 days). Drugs were given intraperitoneal in the morning. PD administration prevented the LPS-induced gut inflammation observed in damage of epithelial barrier, disruption of goblet cells, and condensation of lamina propria (LP). The LPS-induced oxidative stress characterized by decreased superoxide dismutase (SOD) activity and increased lipid hydroperoxide (LOOH) ( < 0.001 for both), and enhanced interleukine-6 (IL-6) & tumor necrosis factor-α (TNF-α) ( < 0.001 for both) as well as immunointensity of NT ( < 0.01) and NTR-1 ( < 0.05) were reversed and normalized to control after PD treatment. Thus, the anti-inflammatory, anti-oxidative, and cell proliferation properties of PD modulate the gut toxicity in LPS-challenged mice.
肠道神经内分泌与免疫成分之间的相互作用维持着机体的身心健康。这种相互作用的破坏可能反映在诸如炎症性肠病（IBD）和精神疾病等病症中。脂多糖（LPS）会破坏内分泌 - 免疫稳态，导致肠道毒性。神经降压素受体 -1（NTR -1）激动剂PD 149163（PD）在精神疾病中作为一种非典型抗精神病药物发挥作用，但其在调节肠道病理生理学中的作用尚不清楚。因此，本研究的目的是评估PD对LPS诱导的肠道毒性的保护作用。将12周龄的瑞士白化雌性小鼠分为六组（每组n = 6）：（I）对照组，（II）LPS组（1 mg/kg，连续5天），（III）LPS组（1 mg/kg，连续5天） + 低剂量PD组（100 μg/kg，连续21天），（IV）LPS组（1 mg/kg，连续5天） + 高剂量PD组（300 μg/kg，连续21天），（V）低剂量PD组（100 μg/kg，连续21天），以及（VI）高剂量PD组（300 μg/kg，连续21天）。药物于上午腹腔注射。给予PD可预防在LPS诱导的肠道炎症中观察到的上皮屏障损伤、杯状细胞破坏和固有层（LP）浓缩。LPS诱导的氧化应激表现为超氧化物歧化酶（SOD）活性降低和脂质氢过氧化物（LOOH）增加（两者均P < 0.001），以及白细胞介素 -6（IL -6）和肿瘤坏死因子 -α（TNF -α）增强（两者均P < 0.001），以及神经降压素（NT）免疫强度增加（P < 0.01）和NTR -1免疫强度增加（P < 0.05），在PD治疗后均恢复并恢复至对照水平。因此，PD的抗炎、抗氧化和细胞增殖特性可调节LPS攻击小鼠的肠道毒性。
