l -Methionine and silymarin: A comparison of prophylactic protective capabilities in acetaminophen-induced injuries of the liver, kidney and cerebral cortex

• Published in: Biomedicine & pharmacotherapy 2017-01, Vol.85, p.323-333
• Main Authors: Onaolapo, Olakunle J, Adekola, Moses A, Azeez, Taiwo O, Salami, Karimat, Onaolapo, Adejoke Y
• Format: Article
• Language: English
• Subjects: Acetaminophen; Animals; Antioxidant; Antioxidants - pharmacology; Anxiety - chemically induced; Anxiety - metabolism; Anxiety - prevention & control; Behavior, Animal - drug effects; Biomarkers - metabolism; Brain Diseases - chemically induced; Brain Diseases - metabolism; Brain Diseases - pathology; Brain Diseases - prevention & control; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - pathology; Chemical and Drug Induced Liver Injury - prevention & control; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; Drug overdose; Grooming - drug effects; Internal Medicine; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Kidney Diseases - chemically induced; Kidney Diseases - metabolism; Kidney Diseases - pathology; Kidney Diseases - prevention & control; l-Methionine; Liver - drug effects; Liver - metabolism; Liver - pathology; Medical Education; Memory, Short-Term - drug effects; Methionine - pharmacology; Motor Activity - drug effects; Organ Specificity; Oxidative stress; Oxidative Stress - drug effects; Rats, Wistar; Silymarin; Silymarin - pharmacology; Spatial Memory - drug effects; Time Factors; Weight Gain - drug effects
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2016.11.033

Abstract We compared the relative protective abilities of silymarin and l -methionine pre-treatment in acetaminophen overdose injuries of the liver, kidney and cerebral cortex by assessing behaviours, antioxidant status, tissue histological changes and biochemical parameters of hepatic/renal function. Rats were divided into six groups of ten each; animals in five of these groups were pre-treated with oral distilled water, silymarin (25 mg/kg) or l -methionine (2.5, 5 and 10 mg/kg body weight) for 14 days; and then administered intraperitoneal (i.p.) acetaminophen at 800 mg/kg/day for 3 days. Rats in the sixth group (normal control) received distilled water orally for 14 days and then i.p. for 3 days. Neurobehavioural tests were conducted 7 days after last i.p treatment, and animals sacrificed on the 8th day. Plasma was assayed for biochemical markers of liver/kidney function; while sections of the liver, kidney and cerebral cortex were either homogenised for assay of antioxidant status or processed for histology. Acetaminophen overdose resulted in locomotor retardation, excessive self-grooming, working-memory impairment, anxiety, derangement of liver/kidney biochemistry, antioxidant imbalance, and histological changes in the liver, kidney and cerebral cortex. Administration of silymarin or increasing doses of l -methionine counteracted the behavioural changes, reversed biochemical indices of liver/kidney injury, and improved antioxidant activity. Silymarin and l -methionine also conferred variable degrees of tissue protection, on histology. Either silymarin or l -methionine can protect vulnerable tissues from acetaminophen overdose injury; however, each offers variable protection to different tissues. This study highlights an obstacle to seeking the ‘ideal’ protective agent against acetaminophen overdose.