Ameliorative effect of aqueous leaf extract of Pistacia lentiscus L. against oxaliplatin-induced hepatic injury, oxidative stress, and DNA damage in vitro and in vivo

The current study aimed to assess the preventive effects of aqueous leaf extract of Pistacia lentiscus (ALEPL) against Oxaliplatin (OXA)-induced DNA damage, hepatic injury, and oxidative stress. The in vitro cytotoxic and genotoxic effects of OXA and ALEPL on HCT116 colon cancer cells were evaluated using the MTT (Tetrazolium salt reduction) assay and comet assay. The in vivo study involved 24 female NMRI (Naval Medical Research Institute) mice that were equally divided into four groups as follows: Control group, ALEPL-treated group (100 mg/kg), OXA-treated group (7 mg/kg), and ALEPL-treated group (100mg/kg) + OXA (7mg/kg). All animals were sacrificed 48 h after OXA treatment. Samples of liver and blood were collected for histopathological, micronucleus, and biochemical analyses. Oxidative stress parameters were also evaluated through non-enzymatic and enzymatic antioxidant activities. Our findings demonstrated that ALEPL contains high phenolic compounds. In the MTT assay, OXA exerted the most potent cytotoxic effect, but ALEPL alone showed no toxic effect in HCT116 cells. Furthermore, OXA administration caused significant DNA fragmentation both in vitro and in vivo, elevated serum biochemical parameters, and confirmed acute liver damage through histopathological observations compared to the control group. OXA exposure also led to a decrease in hepatic glutathione (GSH) and an increase in lipid peroxidation and antioxidant enzyme activities. From the results of our study, ALEPL pretreatment significantly restored the hepatic toxicity and DNA damage as well as the oxidative stress profile induced by OXA.