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1.
BJS Open ; 5(1)2021 01 08.
Article in English | MEDLINE | ID: mdl-33609390

ABSTRACT

BACKGROUND: There are currently few effective drugs to treat the leg symptoms of peripheral arterial disease (PAD). Previous studies have suggested that the nutraceutical, quercetin, can improve exercise performance and reduce pain sensitivity in healthy mice and improve blood supply in a rodent model of acute hind-limb ischaemia. These models may not be relevant to people with PAD. The aim of this study was to examine the effect of quercetin on exercise performance, physical activity and blood supply in a novel mouse model of sustained hind-limb ischaemia. METHODS: Hind-limb ischaemia was induced in 6-month-old male apolipoprotein E-deficient mice using a novel two-stage surgical procedure. Five days after induction of ischaemia, mice were allocated to commence dietary quercetin or a control diet for 4 weeks. The primary outcome was exercise performance evaluated using a treadmill test. Other outcomes included physical activity, estimated by an open field test, and hind-limb blood supply, assessed by laser Doppler monitoring. RESULTS: A sustained reduction in relative limb blood supply (P < 0.001) was achieved consistently in all 48 mice before allocation to a control (n = 24) or quercetin (n = 24) diet. Quercetin did not improve exercise performance (P = 0.785), physical activity (P = 0.151) or relative limb blood supply (P = 0.954) over the 4-week assessment period. CONCLUSION: These data suggest that quercetin does not improve exercise performance, physical activity or limb blood supply in mice with sustained hind-limb ischaemia, and therefore is unlikely be an effective treatment for PAD.


Subject(s)
Disease Models, Animal , Hindlimb/physiopathology , Ischemia/drug therapy , Quercetin/pharmacology , Animals , Apolipoproteins E/deficiency , Ischemia/surgery , Male , Mice , Peripheral Arterial Disease/pathology , Physical Functional Performance
2.
Vet J ; 259-260: 105471, 2020.
Article in English | MEDLINE | ID: mdl-32553233

ABSTRACT

The neurotransmitter Substance P, and its neurokinin-1 receptor (NK-1R) are involved in the regulation of many pathophysiological processes including emesis, inflammation and nociceptive processing. This review provides a brief summary of the anti-inflammatory and analgesic properties of experimental NK-1R antagonists followed by a systematic review and meta-analysis on maropitant, the only NK-1R antagonist with a label indication for emesis in veterinary patients. There is very limited evidence based information on the putative clinical utilisation of maropitant for pain and inflammation. The aim of this systematic review and meta-analysis was to evaluate published reports on anti-inflammatory, analgesic and anaesthesia-sparing effects of maropitant. Medline, Pubmed, Science direct and Web of Science were searched to identify all published studies on maropitant, followed by a meta-analysis. Fourteen studies with 128 animals receiving maropitant and 127 controls met the inclusion criteria. Overall, maropitant had a significant inhalation anaesthetic-sparing effect (SMD -0.92, 95% CI -1.30, -0.54; P < 0.00001). However, treatment with maropitant had no effect on pain (SMD 0.06, 95% CI -0.37, 0.48; P = 0.80), or leukocyte cell infiltration in different inflammatory conditions (SMD -0.60, 95% CI -1.31, 0.11; P = 0.10). Based on all eligible studies for this review, it can be deduced that maropitant significantly reduced the minimum alveolar concentrations for isoflurane and sevoflurane for many different surgical procedures but it had no clearly proven effect on inflammation and pain.


Subject(s)
Analgesics/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Quinuclidines/therapeutic use , Analgesics/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Neurokinin-1 Receptor Antagonists/pharmacology , Neurokinin-1 Receptor Antagonists/therapeutic use , Pain/drug therapy , Pain/veterinary , Quinuclidines/pharmacology
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