Preclinical evidence 3
3 studies reported at therapy level; 3 evidence entries itemised.
RatChemical/toxinSprague-Dawleyn = 18 rats per group across three groupsPretreatment before induction of severe acute pancreatitis
Model: Severe acute pancreatitis induced by retrograde pancreatic duct injection of 5% sodium taurocholate, with associated intestinal barrier injury
Wortmannin pretreatment reduced ultrastructural intestinal mucosal damage and gave lower pancreas scores (7.4 plus or minus 1.14, 10.2 plus or minus 1.48 and 12.0 plus or minus 1.58 at 3, 6 and 12 h). Plasma endotoxin and Evans blue content were significantly lower at all timepoints, and phosphoryl…
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MouseWoundKunmingMale and female, analysed separatelyn = 224 male and 120 female Kunming mice, 344 in total; n per g…Intrathecal, into the subarachnoid space between L5 and L6 in conscious mice, 5 microL over 30 secondsWortmannin 0.016, 0.08 and 0.4 microg per 5 microL; LY29400…90 minutes after plantar incision for behavioural experiments; 45 minutes after…
Model: Plantar incision model of postoperative pain: under isoflurane a 5 mm longitudinal incision was made through the glabrous skin and fascia of the right hind paw, the flexor digitorum brevis muscle was elevated and divided, and the skin closed with a single mattress suture
Post-surgical intrathecal wortmannin or LY294002 dose-dependently attenuated mechanical allodynia, thermal hyperalgesia and cumulative pain scores in male mice, with only mild effects in female mice. In male mice the inhibitors partially reduced incision-induced spinal Fos expression and attenuated…
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RatOtherSprague-DawleyMalen = 60 rats randomly divided into four groups
Model: Severe acute pancreatitis with associated thyroid injury, induced surgically (method of induction not stated in the available text)
Wortmannin reduced serum amylase, lipase and thyroid hormone disturbance, attenuated pancreatic and thyroid histological injury and ultrastructural change, lowered thyroid malondialdehyde and serum TNF-alpha, IL-6 and IL-1beta, and reduced AKT, p38 MAPK and NF-kappaB expression in thyroid tissue.
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