{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:29:12Z","timestamp":1787758152854,"version":"build-2784847793"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background and purpose:<\/jats:title>\n                    <jats:p>Hepatic encephalopathy (HE) is a brain dysfunction caused by acute and chronic hepatic failure. The pathogenesis of HE is unknown, although small intestinal bacterial overgrowth associated with chronic liver damage, hyperammonemia, and oxidative stress are considered major factors for HE. Effective lowering of circulating ammonia and neuroinflammation is the main strategy for preventing and treating HE in cirrhosis. In the present study, the protective effect of probiotics (Lactobacillus plantarum and Bacillus clausii) and ascorbic acid in combination was assessed in bile duct ligation (BDL)-induced chronic HE in rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental approach:<\/jats:title>\n                    <jats:p>Sprague Dawley rats were divided into five groups (n = 6). All groups were subjected to double ligation of the bile duct and fed a hyperammonemia diet, except group I (normal control). Groups III and IV were treated with a low and high dose of combination therapy, respectively, while group V was given lactulose. Four weeks post ligation, behavioral, biochemical, and neurochemical parameters were measured. The liver and brain were dissected for histopathology and protein analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings \/ Results:<\/jats:title>\n                    <jats:p>Combination therapy reduced plasma AST, ALT, ALP, and ammonia levels and attenuated hepatic inflammation\/fibrosis in cirrhotic rats. Furthermore, combination therapy significantly improved behavioral parameters and restored the antioxidant enzyme activity. Histological changes were observed in the brain and liver of BDL animals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and implications:<\/jats:title>\n                    <jats:p>The additive impact of probiotics and ascorbic acid on BDL-induced chronic HE in rats was mediated by a reduction in ammonia and oxidative stress, implying the therapeutic potential of combination therapy in HE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/1735-5362.350244","type":"journal-article","created":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T23:03:17Z","timestamp":1657234997000},"page":"445-456","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":5,"title":["Protective effect of probiotics and ascorbic acid on bile duct ligation-induced chronic hepatic encephalopathy in rats"],"prefix":"10.4103","volume":"17","author":[{"given":"Chirag","family":"Patel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lalita","family":"Shahgond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeev","family":"Acharya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai HS.","family":"Boddu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketan","family":"Ranch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-10-20240909","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1093\/gastro\/gox013","article-title":"Hepatic encephalopathy","volume":"5","author":"Ferenci","year":"2017","journal-title":"Gastroenterol Rep"},{"key":"R2-10-20240909","doi-asserted-by":"crossref","first-page":"S29","DOI":"10.1016\/j.jceh.2014.12.003","article-title":"Gut microbiota: its role in hepatic encephalopathy","volume":"5","author":"Rai","year":"2015","journal-title":"J Clin Exp Hepatol"},{"key":"R3-10-20240909","doi-asserted-by":"crossref","first-page":"960","DOI":"10.3390\/nu9090960","article-title":"Vitamin C status and cognitive function: a systematic review","volume":"9","author":"Travica","year":"2017","journal-title":"Nutrients"},{"key":"R4-10-20240909","doi-asserted-by":"crossref","first-page":"140","DOI":"10.3390\/nu10020140","article-title":"The pharmabiotic approach to treat hyperammonemia","volume":"10","author":"Liu","year":"2018","journal-title":"Nutrients"},{"key":"R5-10-20240909","doi-asserted-by":"crossref","first-page":"480309","DOI":"10.1155\/2012\/480309","article-title":"A current review of the diagnostic and treatment strategies of hepatic encephalopathy","volume":"2012","author":"Poh","year":"2012","journal-title":"Int J Hepatol"},{"key":"R6-10-20240909","first-page":"CD008716","article-title":"Probiotics for people with hepatic encephalopathy","volume":"2017","author":"Dalal","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"R7-10-20240909","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s11011-021-00862-w","article-title":"Therapeutic potential of probiotics - Lactobacillus plantarum UBLP40 and Bacillus clausii UBBC07 on thioacetamide-induced acute hepatic encephalopathy in rats","volume":"37","author":"Shahgond","year":"2022","journal-title":"Metab Brain Dis"},{"key":"R8-10-20240909","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.tice.2013.06.001","article-title":"Protective role of antioxidants on thioacetamide-induced acute hepatic encephalopathy: biochemical and ultrastructural study","volume":"45","author":"Mustafa","year":"2013","journal-title":"Tissue Cell"},{"key":"R9-10-20240909","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1742-2094-3-6","article-title":"Cyclooxygenase-2 mediates microglial activation and secondary dopaminergic cell death in the mouse MPTP model of Parkinson\u2019s disease","volume":"3","author":"Vijitruth","year":"2006","journal-title":"J Neuroinflammation"},{"key":"R10-10-20240909","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1093\/ilar\/ilu013","article-title":"Assessing spatial learning and memory in rodents","volume":"55","author":"Vorhees","year":"2014","journal-title":"ILAR J"},{"key":"R11-10-20240909","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0166-4328(88)90157-X","article-title":"A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data","volume":"31","author":"Ennaceur","year":"1988","journal-title":"Behav Brain Res"},{"key":"R12-10-20240909","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/0039-128X(94)90006-X","article-title":"Antioxidant effects of estradiol and 2- hydroxyestradiol on iron-induced lipid peroxidation of rat liver microsomes","volume":"59","author":"Ruiz-Larrea","year":"1994","journal-title":"Steroids"},{"key":"R13-10-20240909","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1016\/j.biopha.2018.06.079","article-title":"Neuroprotective activity of tetramethylpyrazine against 3- nitropropionic acid induced Huntington\u2019s disease-like symptoms in rats","volume":"105","author":"Danduga","year":"2018","journal-title":"Biomed Pharmacother"},{"key":"R14-10-20240909","doi-asserted-by":"crossref","first-page":"469","DOI":"10.5009\/gnl.2013.7.4.469","article-title":"Effects of metabolic syndrome on fibrosis in chronic viral hepatitis","volume":"7","author":"Yoon","year":"2013","journal-title":"Gut Liver"},{"key":"R15-10-20240909","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.bbr.2016.07.011","article-title":"Function of opioidergic and dopaminergic antagonists on both spatial and object novelty detection deficits induced in rodent model of hepatic encephalopathy","volume":"313","author":"Allampati","year":"2016","journal-title":"Behav Brain Res"},{"key":"R16-10-20240909","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.bbr.2016.07.011","article-title":"Function of opioidergic and dopaminergic antagonists on both spatial and object novelty detection deficits induced in rodent model of hepatic encephalopathy","volume":"313","author":"Nasehi","year":"2016","journal-title":"Behav Brain Res"},{"key":"R17-10-20240909","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1002\/hep.21180","article-title":"Brain edema and inflammatory activation in bile duct ligated rats with diet-induced hyperammonemia: a model of hepatic encephalopathy in cirrhosis","volume":"43","author":"Jover","year":"2006","journal-title":"Hepatology"},{"key":"R18-10-20240909","first-page":"305","article-title":"Prolonged bile duct obstruction: a new experimental model for cirrhosis in the rat","volume":"65","author":"Kountouras","year":"1984","journal-title":"Br J Exp pathol"},{"key":"R19-10-20240909","first-page":"540","article-title":"Protective effect of ultrasonication-processed ginseng berry extract on the D-galactosamine\/lipopolysaccharide- induced liver injury model in rats","volume":"42","author":"Nam","year":"2018","journal-title":"JGR"},{"key":"R20-10-20240909","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s12937-016-0186-5","article-title":"The importance of antioxidants which play the role in cellular response against oxidative\/nitrosative stress: current state","volume":"15","author":"Kurutas","year":"2015","journal-title":"Nutr J"},{"key":"R21-10-20240909","doi-asserted-by":"crossref","first-page":"3405","DOI":"10.2147\/DDDT.S83144","article-title":"Effect of vitamin C on inflammation and metabolic markers in hypertensive and\/or diabetic obese adults: a randomized controlled trial","volume":"9","author":"Ellulu","year":"2015","journal-title":"Drug Des Devel Ther"},{"key":"R22-10-20240909","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.jcma.2017.03.010","article-title":"Ascorbate lacks significant influence in rats with bile duct ligation-induced liver injury","volume":"80","author":"Ho","year":"2017","journal-title":"J Chin Med Assoc"},{"key":"R23-10-20240909","doi-asserted-by":"crossref","first-page":"578386","DOI":"10.3389\/fimmu.2021.578386","article-title":"Anti-inflammatory and immunomodulatory effects of probiotics in gut inflammation: a door to the body","volume":"12","author":"Cristofori","year":"2021","journal-title":"Front Immunol"},{"key":"R24-10-20240909","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1016\/j.jceh.2014.06.004","article-title":"Pathogenesis of hepatic encephalopathy: role of ammonia and systemic inflammation","volume":"5","author":"Aldridge","year":"2015","journal-title":"J Clin Exp Hepatol"},{"key":"R25-10-20240909","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1097\/00005072-198507000-00004","article-title":"Morphologic effects of ammonia on primary astrocyte cultures. II. electron microscopic studies","volume":"44","author":"Gregorios","year":"1985","journal-title":"J Neuropathol Exp Neurol"},{"key":"R26-10-20240909","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1023\/A:1020688925901","article-title":"Astroglial dysfunction in hepatic encephalopathy","volume":"13","author":"Norenberg","year":"1998","journal-title":"Metab Brain Dis"},{"key":"R27-10-20240909","first-page":"618","article-title":"A light and electron microscopic study of experimental portal-systemic (ammonia) encephalopathy. Progression and reversal of the disorder","volume":"36","author":"Norenberg","year":"1977","journal-title":"Lab Invest"},{"key":"R28-10-20240909","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1016\/j.jceh.2014.07.006","article-title":"Neuroinflammation in hepatic encephalopathy: mechanistic aspects","volume":"5","author":"Jayakumar","year":"2015","journal-title":"J Clin Exp Hepatol"},{"key":"R29-10-20240909","doi-asserted-by":"crossref","first-page":"125","DOI":"10.3389\/fncel.2013.00125","article-title":"Thyroid hormone treated astrocytes induce maturation of cerebral cortical neurons through modulation of proteoglycan levels","volume":"7","author":"Dezonne","year":"2013","journal-title":"Front cell neurosci"},{"key":"R30-10-20240909","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.jceh.2018.06.007","article-title":"Hyperammonemia in hepatic encephalopathy","volume":"8","author":"Jayakumar","year":"2018","journal-title":"J Clin Exp Hepatol"},{"key":"R31-10-20240909","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jphysparis.2005.12.082","article-title":"Synaptic plasticity, astrocytes and morphological homeostasis","volume":"99","author":"Slezak","year":"2006","journal-title":"J Physiol- Paris"},{"key":"R32-10-20240909","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/glia.20082","article-title":"Role for glia in synaptogenesis","volume":"47","author":"Ullian","year":"2004","journal-title":"Glia"},{"key":"R33-10-20240909","doi-asserted-by":"crossref","first-page":"463","DOI":"10.3390\/ijms22010463","article-title":"The Association between hepatic encephalopathy and diabetic encephalopathy: the brain-liver axis","volume":"22","author":"Cheon","year":"2021","journal-title":"Int J Mol Sci"}],"container-title":["Research in Pharmaceutical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/1735-5362.350244","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:04:29Z","timestamp":1787756669000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/1735-5362.350244"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022]]}},"URL":"https:\/\/doi.org\/10.4103\/1735-5362.350244","relation":{},"ISSN":["1735-5362"],"issn-type":[{"value":"1735-5362","type":"print"}],"subject":[],"published":{"date-parts":[[2022,8]]}}}