Giri SR, Bhoi B, Trivedi C, Rath A, Jadhav V, Palode S, Ranvir R, Patel A, Sundar R, Patel H, Jain MR. Saroglitazar ameliorates alcoholic liver disease and is associated with enhanced ethanol metabolism. World J Hepatol 2026; 18(7): 120153 [DOI: 10.4254/wjh.120153]
Corresponding Author of This Article
Suresh R Giri, PhD, Zydus Research Centre, Zydus Lifesciences Limited, Sarkhej-Bavla Highway No. 8A, Moraiya, Ahmedabad 382213, Gujarat, India. sureshgiri@zyduslife.com
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Gastroenterology & Hepatology
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research-article
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World J Hepatol. Jul 27, 2026; 18(7): 120153 Published online Jul 27, 2026. doi: 10.4254/wjh.120153
Saroglitazar ameliorates alcoholic liver disease and is associated with enhanced ethanol metabolism
Suresh R Giri, Bibhuti Bhoi, Chitrang Trivedi, Akshyaya Rath, Vighnesh Jadhav, Sandip Palode, Ramchandra Ranvir, Ashvin Patel, Rajesh Sundar, Hiren Patel, Mukul R Jain
Suresh R Giri, Bibhuti Bhoi, Chitrang Trivedi, Akshyaya Rath, Vighnesh Jadhav, Sandip Palode, Ramchandra Ranvir, Ashvin Patel, Rajesh Sundar, Hiren Patel, Mukul R Jain, Zydus Research Centre, Zydus Lifesciences Limited, Ahmedabad 382213, Gujarat, India
Author contributions: Giri SR, Bhoi B, and Jain MR designed and coordinated the study, drafted the manuscript; Giri SR, Sundar R, and Jain MR supervised the project and were responsible for project administration and funding acquisition; Bhoi B, Trivedi C, Rath A, Jadhav V, Palode S, Patel A, and Patel H performed the experiments, acquired the data, and conducted data analysis; Ranvir R, Patel A, Sundar R, and Patel H reviewed and interpreted the data; all authors critically reviewed the manuscript and approved the final version.
Institutional animal care and use committee statement: All animal procedures were reviewed and approved by the Institutional Animal Ethics Committee of Zydus Research Centre, Zydus Lifesciences Limited, under protocol No. ZRC/PH/BP/049/02-2K23.
Conflict-of-interest statement: All authors are employees of Zydus Lifesciences Limited, Ahmedabad, India and do not have any conflicts of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The datasets generated and analysed during the current study are available from the corresponding author upon reasonable request. No additional data are available.
Corresponding author: Suresh R Giri, PhD, Zydus Research Centre, Zydus Lifesciences Limited, Sarkhej-Bavla Highway No. 8A, Moraiya, Ahmedabad 382213, Gujarat, India. sureshgiri@zyduslife.com
Received: February 24, 2026 Revised: April 23, 2026 Accepted: June 15, 2026 Published online: July 27, 2026 Processing time: 157 Days and 22.5 Hours
Abstract
BACKGROUND
Alcoholic liver disease (ALD), or alcohol-related liver disease, is a major global cause of morbidity and mortality, encompassing a spectrum of conditions from simple steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Alcohol consumption contributes to approximately 5.3% of global deaths and 5.1% of the worldwide burden of disease and injury. With approximately 43% of the global population consuming alcohol, it remains a key driver of liver damage, accounting for nearly 60% of cirrhosis cases in Europe, North America, and Latin America. There remains an unmet need for effective treatments that can reverse or prevent alcohol-induced liver disease.
AIM
To determine whether saroglitazar could prevent or improve alcohol-induced liver injury in the widely used National Institute on Alcohol Abuse and Alcoholism model using C57 mice.
METHODS
Under the preventive study design, male C57BL/6 mice (8-10 weeks old) were fed on a Lieber-DeCarli diet containing 5% (v/v) ethanol were orally administered saroglitazar at 0.4 mg/kg and 0.8 mg/kg doses for 10 days. In the therapeutic study design, animals were fed with a liquid ethanolic (4%) diet for 4 weeks and after confirming the presence of ALD, the mice were administered saroglitazar at doses of 0.4 mg/kg or 0.8 mg/kg orally once daily for 4 weeks.
RESULTS
In both study designs, saroglitazar significantly attenuated ethanol-induced elevations in plasma alanine aminotransferase and plasma ethanol concentration. Changes in plasma ethanol were accompanied by significantly elevated plasma acetate levels, a non-toxic alcohol metabolite, increased hepatic aldehyde dehydrogenase 2 activity and upregulated expression of alcohol dehydrogenase genes. In the therapeutic study design saroglitazar resulted in complete reversal of hepatic lipid accumulation and significant improvement in liver histology. The comparator hepatoprotective reference compound, ursodeoxycholic acid, did not produce any significant improvement in ethanol metabolism, although it significantly reduced liver injury markers such as plasma alanine aminotransferase and aspartate aminotransferase.
CONCLUSION
Saroglitazar is associated with altered alcohol metabolism, significantly improves plasma and liver biomarkers associated with ALD and highlights its potential as a promising therapeutic candidate for the treatment of ALD.
Core Tip: Alcoholic liver disease is one of the major causes of morbidity worldwide and there is an unmet need for a drug to prevent or treat this condition. Saroglitazar, which is approved in India for the treatment of metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis, showed beneficial effect like reduction in alanine aminotransferase, aspartate aminotransferase and hepatic triglyceride in animal model of alcoholic liver disease. Saroglitazar effectively altered the alcohol metabolism markers, thus reducing the alcohol-induced liver damage.
