title: Serum microRNAs-217 and -375 as biomarkers of acute pancreatic injury in rats.
abstract: Pancreatic injury in rats is primarily detected through histopathological changes and conventional serum biomarkers such as amylase and lipase. However, amylase and lipase have a short half-life and are markers of acinar, not islet cell injury. We investigated whether circulating microRNA (miR) levels that are enriched in acinar cells (miR-217, miR-216a/b) or islet cells (miR-375) could serve as markers of pancreatic injury. Rats were treated with a single dose of either vehicle, streptozotocin (STZ), caerulein, or acetaminophen (APAP), and necropsied at 4, 24, and 48h. Pancreas, liver, heart, kidney and skeletal muscle were analyzed for histopathology. Blood was collected at necropsy and processed to serum for amylase/lipase enzymatic determinations and miR qPCR analysis. Caerulein induced degeneration/necrosis of acinar cells at 4h that persisted for 48h. Caerulein-induced injury was associated with increases in serum amylase/lipase (4h), miR-216a/b (4, 24h). In contrast, serum miR-217 was detected at all time points examined. STZ did not induce increases in either amylase or lipase but did induce increases in miR-375 levels at 4 and 24h. No increases in miR-375 were observed in caerulein-treated rats, and no increases were observed in miR-217 and miR-216a/b in STZ-treated rats. APAP induced centrilobular necrosis in the liver 24h after treatment, but did not induce pancreatic injury or increases in miR-217 or miR-375. Our results suggest that miR-217 and miR-375 represent promising biomarkers of pancreatic injury in rats.
authors: Drug Safety Evaluation, Bristol-Myers Squibb, 1 Squibb Drive, New Brunswick, NJ 08903, United States. Electronic address: Jacqueline.Calvano@bms.com.
authors: Jacqueline
authors: J
authors: Calvano
authors: Drug Safety Evaluation, Bristol-Myers Squibb, 1 Squibb Drive, New Brunswick, NJ 08903, United States.
authors: Gwendolyn
authors: G
authors: Edwards
authors: Drug Safety Evaluation, Bristol-Myers Squibb, 1 Squibb Drive, New Brunswick, NJ 08903, United States.
authors: Clifford
authors: C
authors: Hixson
authors: Drug Safety Evaluation, Bristol-Myers Squibb, 1 Squibb Drive, New Brunswick, NJ 08903, United States.
authors: Holly
authors: H
authors: Burr
authors: Drug Safety Evaluation, Bristol-Myers Squibb, 1 Squibb Drive, New Brunswick, NJ 08903, United States.
authors: Raja
authors: R
authors: Mangipudy
authors: Drug Safety Evaluation, Bristol-Myers Squibb, 1 Squibb Drive, New Brunswick, NJ 08903, United States.
authors: Mark
authors: M
authors: Tirmenstein
mesh_terms: D000082:Acetaminophen; D061354:Acinar Cells / Q000473:pathology; D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D002108:Ceruletide; D004195:Disease Models, Animal; D006207:Half-Life; D007515:Islets of Langerhans / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008049:Lipase / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D010179:Pancreas / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
chemical_list: D015415:Biomarkers; C578536:MIRN216 microRNA, rat; C574979:MIRN375 microRNA, rat; D035683:MicroRNAs; D000082:Acetaminophen; D013311:Streptozocin; D002108:Ceruletide; D008049:Lipase; D000681:Amylases
keywords: Biomarker; MiR-216a/b; MiR-217; MiR-375; Pancreatic; miRNA