platonin and Sepsis

Vascular hyporeactivity contributes to hemodynamic alterations and circulatory failure in severe sepsis. Among the identified mechanisms, inflammation and oxidative stress are the most crucial ones in mediating the development of vascular hyporeactivity induced by sepsis. Platonin, a photosensitive dye and an antioxidant, possesses potent antiinflammation effects. We elucidated whether platonin could mitigate vascular hyporeactivity of thoracic aorta in septic rats.. Adult male Sprague-Dawley rats were randomized to receive sham operation (Sham), Sham plus platonin (100 μg/kg), cecal ligation and puncture (CLP), or CLP plus platonin (10, 50, or 100 μg/kg) and designated as the Sham, P, CLP, CLP + P(10), CLP + P(50), and CLP + P(100) group, respectively (n = 6 in each group). After maintaining for 12 hours, surviving rats were euthanized and thoracic aorta was isolated and vascular reactivity of aortic rings was determined.. Vascular reactivity induced by vasoconstrictors phenylephrine and angiotensin II of the Sham and the P groups (n = 6 in both groups) were similar, whereas vascular reactivity of the CLP group (n = 5) were significantly lower than those of the Sham group (both P < 0.001). Of note, vascular reactivity induced by phenylephrine and angiotensin II of the CLP + P(10) group (n = 5) and the CLP group were not significantly different. In contrast, vascular reactivity induced by phenylephrine and angiotensin II of the CLP + P(50) and the CLP + P(100) groups (n = 6 in both groups) were significantly higher than those of the CLP group (phenylephrine: P = 0.024 and 0.017; angiotensin II: P = 0.031 and 0.036).. Platonin could mitigate vascular hyporeactivity of thoracic aorta in septic rats.

Topics: Animals; Aorta, Thoracic; Cyclooxygenase 2; Dinoprostone; Drug Evaluation, Preclinical; Male; Random Allocation; Rats, Sprague-Dawley; Sepsis; Thiazoles; Vasoconstriction

Platonin possesses potent anti-inflammatory and antioxidative capacities. Because systemic inflammation and oxidative stress are crucial in mediating sepsis-induced blood-brain barrier (BBB) integrity loss, this study elucidated the effects of platonin on preserving BBB integrity in septic rats.. A total of 72 adult male rats (200-250 g) were randomized to receive cecal ligation and puncture (CLP), CLP plus platonin, sham operation, or sham operation plus platonin (n = 18 in each group). Systemic inflammation and oxidation levels and BBB integrity in the surviving rats were determined after 24-hour monitoring.. Plasma levels of interleukin-6 (IL-6) and malondialdehyde (MDA)-markers of systemic inflammation and oxidation-and the grading of Evans blue staining of the brains, BBB permeability to Evans blue dye, and brain edema levels-markers of BBB integrity-in rats that received CLP were significantly higher than rats that received sham operation (all p < 0.001). By contrast, the plasma levels of IL-6 (p < 0.001) and MDA (p < 0.001), and the grading of Evans blue staining (p = 0.015), BBB permeability to Evans blue dye (p = 0.043), and brain edema levels (p = 0.034) in rats that received CLP plus platonin were significantly lower than rats that received CLP. Experimental data further revealed that the concentration of tight junction protein claudin-5, a major structural component of BBB, in rats that received CLP was significantly lower than rats that received CLP plus platonin (p = 0.023).. Platonin could attenuate sepsis-induced BBB integrity loss in rats.

Topics: Animals; Blood-Brain Barrier; Brain Edema; Claudin-5; Interleukin-6; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Sepsis; Thiazoles