Human colon microbiota produce a metabolite called urolithin A (URO A) from ellagic acid and linked compounds, and this metabolite has been demonstrated to have antioxidant, anti-inflammatory, and antiapoptotic activities. The current work examines the various mechanisms through which URO A protects against doxorubicin (DOX)-induced liver injury in Wistar rats. In this experiment, Wistar rats were administered DOX intraperitoneally (20 mg kg−1) on day 7 while given URO A intraperitoneally (2.5 or 5 mg kg−1 d−1) for 14 days. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT) were measured. Hematoxylin and eosin (HE) staining was used to evaluate histopathological characteristics, and then antioxidant and anti-inflammatory properties were evaluated in tissue and serum, respectively. We also looked at how active caspase 3 and cytochrome c oxidase were in the liver. The findings demonstrated that supplementary URO A therapy clearly mitigated DOX-induced liver damage. The antioxidant enzymes SOD and CAT were elevated in the liver, and the levels of inflammatory cytokines, such as TNF-α, NF-kB, and IL-6, in the tissue were significantly attenuated, all of which complemented the beneficial effects of URO A in DOX-induced liver injury. In addition, URO A was able to alter the expression of caspase 3 and cytochrome c oxidase in the livers of rats that were subjected to DOX stress. These results showed that URO A reduced DOX-induced liver injury by reducing oxidative stress, inflammation, and apoptosis.

Doxorubicin (DXR) is an anthracycline antibiotic that is commonly used in cancer treatment. The purpose of this study was to see if Thymoquinone (THY) could reduce the hepatotoxic effects of doxorubicin. All animals were divided into four groups: control (Phosphate buffer i.p. 0.5mlkg -1 /day), THY (10mgkg -1 /i.p/daily), doxorubicin (20mgkg -1 /i.p/single dose), THY (10mgkg -1 /i.p/daily) + DOX(20mgkg -1 /i.p/single dose on Day 7). Changes in hepatic enzymes in serum ALT, AST, and GGT, as well as tests for free radical metabolism enzymes such as Cu, Zn-SOD, CAT, and MDA were carried out in all animals that received treatments. In addition, the inflammatory markers IL-6, Nf-kB, and TNF-alpha were measured in liver tissue homogenate. Caspase, an apoptosis marker, was also measured. The liver enzymes were significantly elevated in DOX treated rats as compared to all treated groups. Thymoquinone pretreatment significantly reduced the level of hepatic enzymes as compared to DOX. Comparison of the DOX-treated group to the control group showed that SOD and catalase activities rose significantly. In the DOX-treated group, malondialdehyde levels were higher than in the control and all-treatment groups, respectively (P<0.05). The THY + DOX group had lower levels of malondialdehyde, SOD, and catalase activity than the DOX-group (P<0.05). Anti-inflammatory markers , as well as Caspase 3 (p<0.0001), reduced in THY-treated rats, were found to be significantly lower in THY-treated rats (P<0.0001). Biochemical findings were supported by histopathological studies. We conclude that by modulating ROS, inflammation, and apoptosis, thymoquinone significantly reduces DOX-induced hepatotoxicity in rats.