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. 2025 Sep;83(3):2961-2975.
doi: 10.1007/s12013-025-01679-5. Epub 2025 Jan 29.

Neurotensin via Type I Receptor Modulates the Endotoxemia Induced Oxido-Inflammatory Stress on the Sympathetic Adrenomedullary System of Mice Regulating NF-κβ/Nor-Epinephrine Pathway

Asheesh Kumar Tiwari  1 , Banalata Mohanty  2
Affiliations

Neurotensin via Type I Receptor Modulates the Endotoxemia Induced Oxido-Inflammatory Stress on the Sympathetic Adrenomedullary System of Mice Regulating NF-κβ/Nor-Epinephrine Pathway

Asheesh Kumar Tiwari et al. Cell Biochem Biophys. 2025 Sep.

Abstract

The present study investigated the role of the neurotensin/NTS in the modulation of the lipopolysaccharide/LPS induced dysfunction of the sympatho-adrenal-medullary system/SAM using both the NTS receptor 1/NTSR1 agonist PD149163/PD and antagonist SR48692 /SR. Forty eight mice were maintained in eight groups; Group I/control, Groups II, III, IV, and VII received LPS for 5 days further Group III/IV/VII received PD low dose/PDL, PD high dose /PDH and SR for 28 days respectively. Group V/VI received similar only PDL and PDH dose respectively whereas Group VIII was exposed to only SR for 28 days. Adrenal tissues histopathology examined through hematoxylin-eosin staining. The plasma levels of pro-inflammatory mediators (NF-kβ, TNF-α, IL-6), IL-10, corticosterone/CORT, nor-epinephrine/NE and NTS were assessed through ELISA. Biochemical detection was adopted to check the level of oxidative stress, assessed by measuring the thiobarbituric acid reactive substance/TBARS, superoxide dismutase/SOD and catalase/CAT in adrenal tissue to determine the therapeutic effect of NTS receptor 1 analogs. Compared with LPS group, PD ameliorated the adrenal medulla histopathology by significantly decreasing pro-inflammatory mediators, CORT and NE as well as enhancing IL-10, normalizing NTS level via down-regulating NF-κβ level. PD inhibited the oxidative stress in SAM system of adrenal by reducing TBARS, while enhancing SOD and CAT activity via regulating the CORT and NE levels. Conversely, SR administration could not normalize the deleterious effect caused by the LPS due to up-regulation of NF-κβ level. Therefore, PD ameliorates the inflammation and oxidative stress of SAM system by inhibiting NF-kβ/NE signaling pathway. Thus, PD could be used as a biological tool in SAM dysfunction for therapeutic evaluation of chronic inflammatory diseases.

Keywords: Adrenal; Catecholamines; Inflammation; Lipopolysaccharide; Neurotensin; Sympatho-adrenal-medullary.

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Conflict of interest statement

Compliance with Ethical Standards. Conflict of Interest: The authors declare no competing interests.

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