Statins as an alternative therapy to alleviate hepatic encephalopathy in cirrhotic mice | [Abstract Book on International Conference on Sustainable Agriculture and Food Security, August 27-31, 2023 • 2023]

Author(s):

1. Subas Aroob: Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences (UVAS), Lahore, Punjab-Pakistan

2. Qamar Niaz: Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences (UVAS), Lahore, Punjab-Pakistan

3. M. Ovais Omer: Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences (UVAS), Lahore, Punjab-Pakistan

4. Syed M. Muneeb Anjum: Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences (UVAS), Lahore, Punjab, Pakistan

5. Ghulam Mustafa: Department of Pathology, University of Veterinary and Animal Sciences (UVAS), Lahore, Punjab-Pakistan

6. M. Adil Rasheed: Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences (UVAS), Lahore, Punjab-Pakistan

7. M. Shafique: Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences (UVAS), Lahore, Punjab-Pakistan

8. Sania Mehreen: Department of Zoology, University of Veterinary and Animal Sciences (UVAS), Lahore, Punjab-Pakistan

9. M. Bilal Khan: Department of Zoology, Quaid-i-Azam, University, Islamabad, Pakistan

10. Fazli Azim: Isolation Hospital and Infections Treatment Centre, Pakistan Institute of Medical Sciences (PIMS), Islamabad, Pakistan

Abstract:

Hepatic encephalopathy (HE) is a severe neurological disorder found in individuals with liver cirrhosis, linked to elevated ammonia levels as a neurotoxin. Current therapies targeting ammonia reduction necessitate exploration of alternative treatments. Statins, cholesterol-lowering agents, possess anti-inflammatory and anti-fibrotic effects in liver cirrhosis. Therefore, we investigate the atorvastatin effect on HE in cirrhotic mice. Male albino mice were randomly selected and divided into Sham (control) and bile duct ligated (cirrhotic) groups i.e., Sham/Saline, Sham/Ator (atorvastatin) -14days (15 mg/kg body weight), Sham/Ator-14days (30 mg/kg body weight) and Sham/Lac (lactulose)-14days (8 mg/kg body weight ) and Bile Duct Ligation (BDL)/Saline, BDL/Ator-14days (15 mg/kg body weight ), BDL/Ator-14days (30 mg/kg body weight) and BDL/Lac-14days ( 8 mg/kg body weight). BDL surgery was performed to induce liver cirrhosis for 28 days while sham operation was used as control. Sham and BDL groups were orally gavaged normal saline, atorvastatin and lactulose for respective days. Liver and brain (forebrain) histopathology was performed to see for fibrosis and inflammation and vacuolar degeneration respectively. Behavioral studies were performed for cognitive and motor functions. Plasma ammonia level was monitored as a marker for HE. Liver function tests i.e., alanine transaminase (ALT) and aspartate transaminase (AST) were evaluated to see for liver toxicity. The findings showed that atorvastatin treatment at 30 mg/kg body weight in BDL mice improved the cognitive and behavior functions as compared to atorvastatin-treated BDL mice (15 mg/kg body weight). The atorvastatin-treated group at 30 mg/kg body weight decreased the inflammation and fibrosis in liver cirrhosis in BDL mice as compared to atorvastatin-treated BDL mice (15 mg/kg body weight). The plasma ammonia, cholesterol, ALT and AST levels were also decreased in atorvastatin-treated BDL mice at 30 mg/kg body weight in comparison to atorvastatin-treated BDL mice at 15 mg/kg body weight. The plasma bilirubin level was not affected in both saline-treated BDL and atorvastatin treated BDL groups (both groups). The brain histopathology showed that the vacuolar degeneration was decreased in atorvastatin-treated BDL mice at 30 mg/kg body weight as compared to atorvastatin-treated BDL mice at 15 mg/kg body weight. Conclusions: The atorvastatin at 30 mg/kg body weight alleviates the HE by decreasing the plasma ammonia, brain vacuolar degeneration and ALT and AST levels in cirrhotic mice.

Page(s): 41-41

DOI: DOI not available

Published: Journal: Abstract Book on International Conference on Sustainable Agriculture and Food Security, August 27-31, 2023 , Volume: 0, Issue: 0, Year: 2023

Keywords:

Ammonia , Hepatic encephalopathy HE , atorvastatin , Bile Duct Ligation BDL , Ammonia , mice

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