Selegiline And Sepsis

Wolf

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Adjuvant Potential of Selegiline in Attenuating Organ Dysfunction in Septic Rats with Peritonitis
"Selegiline, an anti-Parkinson drug, has antioxidant and anti-apoptotic effects. To explore the effect of selegiline on sepsis, we used a clinically relevant animal model of polymicrobial sepsis. Cecal ligation and puncture (CLP) or sham operation was performed in male rats under anesthesia. Three hours after surgery, animals were randomized to receive intravenously selegiline (3 mg/kg) or an equivalent volume of saline. The administration of CLP rats with selegiline (i) increased arterial blood pressure and vascular responsiveness to norepinephrine, (ii) reduced plasma liver and kidney dysfunction, (iii) attenuated metabolic acidosis, (iv) decreased neutrophil infiltration in liver and lung, and (v) improved survival rate (from 44% to 65%), compared to those in the CLP alone rats. The CLP-induced increases of plasma interleukin-6, organ superoxide levels, and liver inducible nitric oxide synthase and caspase-3 expressions were ameliorated by selegiline treatment. In addition, the histological changes in liver and lung were significantly attenuated in the selegiline -treated CLP group compared to those in the CLP group. The improvement of organ dysfunction and survival through reducing inflammation, oxidative stress and apoptosis in peritonitis-induced sepsis by selegiline has potential as an adjuvant agent for critical ill."
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" The treatment with SEL significantly prevented the severe hypotension at 18 h after CLP (p<0.01, vs. CLP group). However, the CLP-induced tachycardia was not attenuated in rats treated with SEL."

"The CLP surgery caused time–dependent increases in plasma levels of ALT, AST, LDH, BUN, and creatinine (p<0.05 or 0.01, vs. SOP group; Fig. 3). These increases were significantly attenuated by the treatment of CLP rats with SEL (p<0.01, vs. CLP group), indicating that SEL ameliorates liver and kidney injuries induced by CLP."

"In the SOP groups, no significant increase in plasma IL-6 level was observed during the experimental period, indicating that sham surgery and SEL treatment almost have no effect on plasma IL-6 level. The animals received CLP showed a significantly increase in the plasma level of IL-6 at 9 h (p<0.01, vs. SOP group; Fig. 5A), and then declined to near baseline level. However, the treatment of CLP rats with SEL significantly attenuated the increases in plasma IL-6 level at 9 h (p<0.01, vs. CLP group; Fig. 5A)."

"The protein expression of iNOS was detectable in liver and lung homogenates obtained from the SOP groups, whereas a significant induction of iNOS protein was observed from the CLP rats (p<0.01 in the liver and p<0.05 in the lung, vs. SOP group; Fig. 6A). The treatment of CLP rats with SEL significantly reduced the expression of iNOS (p<0.05, vs. CLP group) in liver and lung. The expression of caspase-3 was significantly higher in liver from the CLP group than from the SOP group (p<0.01; Fig. 6B), whereas the treatment of CLP rats with SEL significantly reduced this caspase-3 expression (p<0.01, vs. CLP group)."

"It has been shown that SEL reduces apoptosis by modulating Bcl-2 and BAX and inhibiting caspase-3 activity in a number of cell types [11], [16], [28]. Indeed, the decreased of the caspase-3 protein expression was also observed in the liver of the CLP + SEL group compared to that of the CLP group of animals in our present study. These results suggest that the beneficial effect of SEL on inflammation, tissue injury or apoptosis is further strengthened by the favorable survival outcome in the CLP group. The SEL-treated CLP animals had a 21% survival benefit over CLP controls."

"However, the current study has some limitations which need to be addressed. First, only one single intravenous dose of SEL was used, and consequently, we cannot exclude the possibility that multiple doses or continuous infusion could yield better outcome. Second, SEL was given at 3 h after CLP, nevertheless, the effect of SEL used in the late phase of sepsis is unknown. Third, this experimental sepsis model could not lead to profound hypoxemia at the end of study, indicating that the CLP is not a suitable experimental model of acute lung injury with significant blood gas exchange impairment, including a severe hypoxemic condition."
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My comments:
3mg/kg is a huge dose of Selgiline and I would not be surprised if smaller amounts taken sublingually to preferentially avoid the L-Meth metabolites and increase Dopamine concentrations similar to the way in which Mucuna works in this study(Nitric Oxide Linked To PD, Mucuna Pruriens Works Through Reducing It) could help prevent excessive expression of iNOS in the body. Looking at the study originally posted by @bdawg you see, "Mp treatment resulted in a significant attenuation of iNOS expression, nitrite content and lipid peroxidation demonstrating that it reduces nitric oxide in PQ-induced Parkinson’s disease." Additionally, the fact that they waited 3 hours is a bit of a bummer. It would have been awesome to have another group that received the Selegeline prior to the surgery.
 
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Wolf

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Selegiline Attenuates Sepsis would be a better title. But I'm not well versed in Technomancy just yet.
 

michael94

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This seems to be ubiquitous among a lot of amphetamine-like substances or what most people would call stimulants. Ephedrine is another common one. Definitely useful and possibly invaluable for acute use but can mask some more fundamental problems long term.
 

michael94

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Selegiline Attenuates Sepsis would be a better title. But I'm not well versed in Technomancy just yet.


From wiktionary:
From Middle English sele (“Happiness, good fortune, bliss; an occasion, period of time”)

So "sele" would be a blissful occasion that comes to an end... one that is limited by time. This stands in contrast to sele-ni-um, and is related to human "cells", whatever those really are.

One of the other definitions for sele is "The right time or opportunity for something"...which would point to selegeline and similar drugs being useful acutely. But its not an opportunity one can afford to waste!

sele - Wiktionary
 

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