Effects of vitamin D3 on liver damage induced by cyclophosphamide

Cyclophosphamide is used as chemotherapeutic drug for patients with cancer, but also has been used as immunosuppressant in organ transplantations. Moreover cyclophosphamide has been widely used in the treatment of rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis too. Anticancer drugs including cyclophosphamide, despite to therapeutic efficacy leads to adverse side effects in various organs due to their toxicity. In this experimental research we aimed to determined liver damage induced by cyclophosphamide and whether vitamin D3 has capability to prevent structural injury of liver by reducing oxidative stress or not. Twenty-four male Wistar-Albino rats were used in this study. Rats were divided into four groups. Group I was used as control, rats in group II were injected 200 mg/kg single dose cyclophosphamide intraperitoneally (i.p) whereas rats in group III were injected 200 mg/kg single dose cyclophosphamide plus oral 50IU/kg/day vitamin D3 for 7 days. Rats in the group IV were administred orally 50IU/kg/day vitamin D3 for 7 days. At the end of the experiment, all animals were killed by decapitation under the anesthesia and their livers were removed. Liver tissues were prepared for analysis of histochemical and TUNEL techniques. Results of study examined and photographed in Olympus BH2 photomicroscope. Tissue sections of rats exposured with cyclophosphamide had mononuclear cell infiltration, inclusion bodies and condensed nuclei in the hepatocytes, increased connective tissue, haemorrhage and vascular congestion. Moreover in the periportal areas macrovesicular steatosis, sinusoidal dilatation, vascular congestion and depletion of glycogen stores were observed. However, those histopathological changes were reduced with the coadministration of cyclophosphamide and vitamin D3. Glycogen contents of hepatocytes were more evident but vascular congestion was also prominent in this group. TUNEL stained sections examined under light microscope. The endothelial cells, Kupffer cells and hepatocytes around the v. centralis of group II had TUNEL positive (+3). TUNEL positivity (+2) of Kupffer cells and hepatocytes around the v. centralis and endothelial cells were reduced by vitamin D3 in the group III. In conclusion, vitamin D3 can be used a prophylactic supplement due to its protection capability against cyclophosphamide-induced liver damage. Thus, adverse side effects may be reduced in diseases that require cyclophosphamide treatment. Key Words: Cyclophosphamide, Liver Damage, Vitamin D3, TUNEL