AbstractBackgroundThe adverse effects of methotrexate (MTX) mainly hepatotoxicity restrict its clinical use. This study was designed to investigate the protective effects of saffron (Crocus sativus) (CS) extract on MTX-induced hepatotoxicity.MethodsTwenty-eight male Wistar rats randomly divided into four equal groups. Except for control, all groups received a single intraperitoneal (i.p.) injection of MTX on the 3rd day of study. The CS extract was given (80 mg/kg i.p.) to rats 3 days before MTX and continued for the next 7 days (Pre&Post-CS group) or administrated after MTX injection and lasted for 7 days (Post-CS group). On the 11th day, all rats were sacrificed and their plasma levels of liver enzymes including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were determined. Also, liver histopathology and hepatic levels of malondialdehyde (MDA), nitric oxide (NO) and super oxidase dismutase (SOD) were evaluated.ResultsThe results showed that MTX significantly incremented plasma levels of AST, ALT, ALP and LDH (all p<0.001) and hepatic MDA and NO levels; whereas, decreased SOD activity. Histological alterations such as early fatty changes were evident in the MTX group. Administration of CS extract at both methods could ameliorate liver enzyme elevation, oxidative/nitrosative stresses and morphological alterations of the liver. Pre-and-post treatment with CS extract showed better protective effects than only post-treatment.ConclusionThe present findings provide showing CS could effectively alleviate MTX-induced hepatotoxicity in rats. Further investigations are recommended to determine the exact mechanisms underlying the hepatoprotective potential of saffron.

Background: Despite using various chemotropic drugs, the therapy strategies of cervical cancer are not satisfactory. Researchers tended to examine anti-proliferative effects of different botanical components such as crocin on several cancers. Objectives: We investigated the anti-cancer mechanisms of crocin and epirubicin combination on cancer cervical cells to use fewer toxic components. Methods: By MTT, Hoechst staining and flowcytometry techniques, cell proliferation inhibitory, and apoptosis induction effects of crocin and epirubisin combination on a cervical cancer cell line (OV2008) were determined. Then, alteration expression of the Bax, Bcl2, and P21 genes were also investigated through real-time polymerase chain reaction (real-time PCR). Results: The MTT results showed that crocin and epirubicin stopped proliferation of OV2008 cells. These substances had a simple additive effect after 72 hours treatment. The Hoechst staining illustrated that apoptosis significantly increased after combination therapy. The results of the cell cycle analysis showed that the percentage of dead cells was increased compared to the control group. Also, the number of cells, introduced in all of cell cycle phases, was changed, too. Moreover, real-Time PCR results showed that epiburicin 3.75 µm/mL and crocin 2000 µm/mL led to Bax and P21 up-regulated and Bcl2 down-regulated. Conclusions:Crocin can be used in companion with fewer dose of chemotropic drugs to get better results in cancer therapy and can be more effective on the reduction of drug resistance due to target the main regulators of apoptosis. Nonetheless, more surveys are needed to enlighten their molecular mechanisms.