Additive Effects
of Mesenchymal Stem Cell-Conditioned Medium and Silymarin in Carbon Tetrachloride-Induced
Liver Injury in Rats
Srinivasamurthy Suresh Kumar, Bairy Laxminarayana Kurady, Samuel Vijay Paul, Rehman
Abdul, Goud Manjunatha, Velamur Ravi Rangarajan and Gandi Avinash
Res. J. Biotech.; Vol. 20(9); 1-6;
doi: https://doi.org/10.25303/209rjbt0106; (2025)
Abstract
Liver diseases remain one of the leading global causes of death, with increasing
mortality over recent decades. Mesenchymal stem cells-conditioned medium (MSCs-CM),
rich in cytokines, growth factors and extracellular vesicles, has shown anti-inflammatory
and regenerative potential. This study evaluates the effect of MSCs-CM on carbon
tetrachloride (CCl₄)- induced liver toxicity in Wistar rats and explores the combined
effect of MSC-CM and silymarin using liver enzyme and antioxidant markers. This
experimental animal study was conducted with sixty adults female Wistar rats. Liver
toxicity was induced by intraperitoneal carbon tetrachloride (CCl₄, 1 ml/kg) thrice
weekly for 28 days. Rats were randomly divided into six groups (n=10 each): normal
control, CCl₄-only toxic control, CCl₄ + low-dose MSCs-CM, CCl₄ + high-dose MSCs-CM,
CCl₄ + silymarin (100 mg/kg orally) and CCl₄ + silymarin + high-dose MSCs-CM. Low
and high doses of MSC-CM (1 ml and 2 ml, respectively) were administered intraperitoneally
over 4 weeks after hepatotoxicity induction. Therapeutic effects were evaluated
by liver enzymes, antioxidant markers and histopathology.
Treatment with low-dose MSCs-CM (Group 3) and high-dose MSCs-CM (Group 4) significantly
reduced liver enzymes compared to the toxic control (p < 0.05). Silymarin (Group
5) and the combination of silymarin with MSCs-CM (Group 6) further reduced levels
with group 6 showing the greatest reduction. Histological analysis of the normal
control group showed intact hepatic architecture. CCl₄-treated rats exhibited periportal
mononuclear cell infiltration and sinusoidal dilation. Low-dose MSC-CM treatment
led to mild perivenular inflammation while high-dose MSC-CM showed reduced inflammation
and improved hepatocyte structure. Silymarin-treated rats displayed moderate sinusoidal
dilation. Notably, combined treatment with high-dose MSC-CM and silymarin restored
near-normal liver architecture. MSCs-CM showed modest anti-hepatotoxic effects in
CCl₄- induced model, improving liver enzymes and histology. These findings suggest
its potential as a supportive therapy, especially in combination with other agents.
