LPS‐induced serum TNF production and lethality in mice: effect of L‐carnitine and some acyl‐derivatives

Ruggiero, Vito; C, D'Urso; Albertoni, Claudio; Campo, Silvia; Foresta, P.; Martelli, E. Arrigoni

doi:10.1155/s0962935193000754

Cited by 19 publications

(19 citation statements)

References 12 publications

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“…Preliminary studies showed that intraperitoneal injection of 10 mg/kg of LPS induced significant amounts of TNF-a and IL-6 in mouse plasma with peak at 1 hour post-administration, which was consistent with that reported previously (Ruggiero et al, 1993;Gozzi et al, 1999). Pretreatment with AN3485 dosedependently decreased LPS-induced plasma levels of TNF-a and IL-6 in mice, with ED 50 and ED 90 values of approximately 8 and 30 mg/kg (Fig.…”

Section: Zymosansupporting

confidence: 91%

Inhibition of Toll-Like Receptor-Mediated Inflammation In Vitro and In Vivo by a Novel Benzoxaborole

Chen¹,

Sexton²,

Gertrudes³

et al. 2012

J Pharmacol Exp Ther

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Pro-inflammatory cytokines play a critical role in the development of autoimmune and inflammatory diseases. Targeting the cytokine environment has proven efficient for averting inflammation. In this study, we reported that, a benzoxaborole analog, inhibited TLR2-, TLR3-, TLR4-, and TLR5-mediated TNF-a, IL-1b, and IL-6 release from human PBMCs and isolated monocytes with IC 50 values ranging from 18 to 580 nM, and the inhibition was mediated at the transcriptional level. Topical administration of AN3485 significantly reduced PMA-induced contact dermatitis and oxazolone-induced delayed-type hypersensitivity in mice, indicating its capability of penetrating skin and potential topical application in skin inflammation. Oral administration of AN3485 showed dose-dependent suppression of LPSinduced TNF-a and IL-6 production in mice with an ED 90 of 30 mg/kg. Oral AN3485, 35 mg/kg, twice a day, suppressed collagen-induced arthritis in mice over a 20-day period. The potent anti-inflammatory activity in in vitro and in vivo disease models makes AN3485 an attractive therapeutic lead for a variety of cutaneous and systemic inflammatory diseases.

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Section: Zymosansupporting

confidence: 91%

Inhibition of Toll-Like Receptor-Mediated Inflammation In Vitro and In Vivo by a Novel Benzoxaborole

Chen¹,

Sexton²,

Gertrudes³

et al. 2012

J Pharmacol Exp Ther

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“…The threshold dose of LPS required to induce this effect in the mouse was 300 µg. Some researchers have found that high doses of LPS induce a biphasic response in which an initial profound and prolonged decrease in temperature (Ruggiero et al, 1993) was followed by hyperthermia and fever (Wang et al, 1997), which may have been seen in this study had an intermediate dose of LPS e.g. 200 µg, been used.…”

Section: Discussionsupporting

confidence: 50%

“…The effect of LPS to decrease Tc has been reported before (Filkins and Luzio, 1968;Ruggiero et al, 1993;Wang et al, 1997;Wardlaw et al, 1971) and may be a dose-related phenomenon (Greer and Rietscjhel, 1978) which challenges the traditional view of LPS as a pyrogen (Cohen et al, 1986;Cooper, 1979;Freedman, 1960;Splawinski et al, 1977). The threshold dose of LPS required to induce this effect in the mouse was 300 µg.…”

Section: Discussionmentioning

confidence: 84%

A biocompatible microdevice for core body temperature monitoring in the early diagnosis of infectious disease

Williamson

Savage

Lingard

et al. 2006

Biomed Microdevices

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The early diagnosis of microbial infection is critical to the clinical instigation of effective post-exposure prophylaxis or therapy. However, diagnosis of infection is often attempted only when there are overt clinical signs, and for some of the serious human pathogens, this may jeopardize the efficacy of therapy. We have used a miniaturised sealed, implantable transponder incorporating a calibrated temperature sensor with an external receiver system, to monitor core body temperature (Tc) remotely. We have observed early changes in the diurnal rhythm of Tc, after infection of mice with bacterial pathogens. Changes in Tc preceded overt clinical signs by 3-10 h following challenge with Yersinia pestis, which causes acute infection, In contrast, changes in Tc were detected 11 days before clinical signs in mice exposed to Burkholderia pseudomallei, which causes a chronic syndrome. Significantly, mice pre-vaccinated against Y.pestis infection showed only slight and transient disruption to the diurnal rhythm for Tc, in the absence of clinical signs, when challenged with 10(6) median lethal doses of Y.pestis. This remote monitoring technology could be used to monitor changes in more than one physiological parameter and extrapolation of these data to the clinic would define the available therapeutic window in which diagnosis and post-exposure prophylaxis could be instigated, after a suspected exposure.

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“…Aureli et al [37] reported that ALCAR reduced both cholesterol and sphingomyelin in the brains of aged rats and proposed that the decrease in sphingomyelin was responsible for the decrease in cholesterol. Treatment with ALCAR has also shown to reverse age-associated increase in the levels of free and esterified cholesterol in plasma [38]. Glycolipids are glycosyl derivatives of lipids involved in a wide array of functions in the central nervous system including cell proliferation, differentiation, neurotransmission and apoptosis [39].…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial modulators improve lipid composition and attenuate memory deficits in experimental model of Huntington’s disease

2015

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3-Nitropropionic acid (3-NP) is an irreversible inhibitor of succinate dehydrogenase and induces neuropathological changes similar to those observed in Huntington's disease (HD). The objective of the present study was to investigate neuroprotective effect of mitochondrial modulators; alpha-lipoic acid (ALA) and acetyl-L-carnitine (ALCAR) on 3-NP-induced alterations in mitochondrial lipid composition, mitochondrial structure and memory functions. Experimental model of HD was developed by administering 3-NP at sub-chronic doses, twice daily for 17 days. The levels of conjugated dienes, cholesterol and glycolipids were significantly increased, whereas the levels of phospholipids (phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine) including cardiolipin were significantly decreased in the mitochondria isolated from the striatum of 3-NP-treated animals. In addition, the difference in molecular composition of each phospholipid class was also evaluated using mass spectrometry. Mitochondria lipid from 3-NP-treated animals showed increased cholesterol to phospholipid ratio, suggesting decreased mitochondrial membrane fluidity. 3-NP administration also resulted in ultra-structural changes in mitochondria, accompanied by swelling as assessed by transmission electron microscopy. The 3-NP administered animals had impaired spatial memory evaluated using elevated plus maze test. However, combined supplementation with ALA + ALCAR for 21 days normalized mitochondrial lipid composition, improved mitochondrial structure and ameliorated memory impairments in 3-NP-treated animals, suggesting an imperative role of these two modulators in combination in the management of HD.

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LPS‐induced serum TNF production and lethality in mice: effect of L‐carnitine and some acyl‐derivatives

Cited by 19 publications

References 12 publications

Inhibition of Toll-Like Receptor-Mediated Inflammation In Vitro and In Vivo by a Novel Benzoxaborole

Inhibition of Toll-Like Receptor-Mediated Inflammation In Vitro and In Vivo by a Novel Benzoxaborole

A biocompatible microdevice for core body temperature monitoring in the early diagnosis of infectious disease

Mitochondrial modulators improve lipid composition and attenuate memory deficits in experimental model of Huntington’s disease

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