Therapeutic and Protective Effects of Undifferentiated Stem Cells Against Paraquat-Induced Liver Inflammation in Rats

Abstract

Paraquat (PQ) is a highly toxic herbicide that can induce oxidative stress, inflammation, and tissue injury, including hepatic injury. Mesenchymal stem/stromal cells have attracted considerable interest because of their immunomodulatory and tissue-repair properties. A total of 65 adult male albino rats were divided into four groups: control (n=8), PQ-treated (n=11), protective UDSC-treated (n=16), and therapeutic UDSC-treated (n=30). The PQ-treated group received two successive intraperitoneal doses of PQ at 7.5 mg/kg during Weeks 3 and 4. The protective group received UDSCs intravenously during Week 3, followed one hour later by a single PQ dose of 7.5 mg/kg. The therapeutic group received two successive PQ doses during Weeks 3 and 4, followed by intravenous UDSC administration at a dose of 2,000 cells/g body weight during Week 6, approximately three weeks after the appearance of inflammatory signs. Liver tissues were subsequently examined histologically using hematoxylin and eosin staining. Inflammatory-cell count was used as a quantitative histopathological parameter, and differences among groups were evaluated using one-way analysis of variance (ANOVA). Paraquat exposure was associated with increased inflammatory-cell infiltration and vascular congestion compared with the control group. UDSC administration was associated with improvement in hepatic histopathological features in both treatment groups. An estimated 25% reduction in inflammatory-cell changes was observed in the protective group, whereas the therapeutic group showed an estimated 45% reduction. The therapeutic group demonstrated a greater apparent reduction in inflammatory-cell infiltration than the protective group. UDSC administration was associated with attenuation of paraquat-associated hepatic inflammatory changes in rats. The findings suggest that UDSCs may have both protective and therapeutic potential, with a greater apparent histopathological improvement observed following therapeutic administration after the development of inflammatory signs. Further studies using standardized histopathological scoring, biochemical liver-function markers, molecular inflammatory and oxidative-stress parameters, and comprehensive statistical analyses are required to confirm these findings and clarify the underlying mechanisms