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Abstract Methotrexate is widely used in the therapy of various types of diseases. It is used as a chemotherapeutic agent for many cancer types and is also used for the treatment of psoriasis, and rheumatoid arthritis. It causes numerous side effects; the most serious side effect is hepatotoxicity. Previous studies revealed that folic acid protected the liver in Mtx treated patients but it might decrease the therapeutic efficacy of the drug. Taurine has antioxidant and antifibrotic properties, few studies were made to investigate its role to protect against the ultrastructural changes and fibrosis induced by Mtx. Hence, the aim of our present study was to investigate the histological changes induced by Mtx and to clarify the possible protective role of taurine and folic acid. Fourty two male albino rats were used and divided into four groups. group I (control group) was subdivided into four subgroups six rat each, group Ia the rats in this group did not receive anything, group Ib the rats in this group received intra-peritoneal saline twice weekly for six weeks, group Ic the rats in this group received folic acid in a dose of 250 mcg/kg using rat gavage needle for six weeks and group Id the rats in this group received taurine at a dose of 1000mg/kg daily using rat gavage needle for six weeks. group II six rats in this group received methotrexate at a dose of 0.5mg/kg by intra-peritoneal injection twice weekly for six weeks. group III six rats in this group received methotrexate at a dose of 0.5mg/kg by intra-peritoneal injection twice weekly for six weeks and at the same time received folic acid in a dose of 250 mcg/kg daily using rat gavage needle. group IV six rats in this group received methotrexate at a dose of 0.5mg/kg by intra-peritoneal injection twice weekly for six weeks and at the same time received taurine at a dose of 1000mg/kg daily using rat gavage needle. The specimens were processed and then examined using both light and electron microscopes. Light microscopic examination of liver sections obtained from control group showed the hepatocytes arranged in cords radiating around a central vein. The hepatocytes were polygonal in form with acidophilic cytoplasm and rounded basophilic nuclei having prominent nucleoli. There was minimal collagen deposition. Electron microscopic examination showed the hepatocyte with large oval or rounded nuclei with one or two nucleoli surrounded by nuclear membrane with peripheral condensation of chromatin. The cytoplasm was occupied by mitochondria, and rough endoplasmic reticulum and some inclusions were also seen in the form of glycogen granules which appeared as coarse, electron dense bodies. Light microscopic examination of liver sections obtained from group II showed marked distortion of hepatic cords in their arrangement around the central veins which also showed congestion and dilatation. The hepatocytes appeared with ill-defined cell boundaries. The blood sinusoids were markedly dilated and congested. Some hepatocytes nuclei showed irregular configuration. On the other hand, there was a marked increase of collagen deposition. Electron microscopic examination showed that the most of the hepatocyte revealed wide areas of degeneration in the form of vacuolation and fat droplets that occupied the major parts of the cytoplasm. The mitochondria were swollen with loss of their cristae. The rough endoplasmic reticulum showed dilatation and fragmentation. Examination of the liver sections obtained from group III revealed improvement in the histological appearance compared to group II. Light microscopic examination of liver sections from this group showed the hepatocytes arranged as radiating cords around a central vein which still showed dilatation and congestion and inflammatory cellular infiltration in the periportal areas was still present. There was incease in collagen deposition. Electron microscopic examination showed that most of the hepatocytes had the ultrastuctural pattern as that of the control group. Some hepatocytes showed interrupted arrangement of rER and loss of mitochondrial cristae. Examination of the liver sections from group IV showed that taurine succeeded to protect against the harmful effects of Mtx on the liver to a reasonable degree. Light microscopic examination of liver sections from this group showed preservation of control pattern of hepatocytes, they were organized around a central vein with sinusoidal spaces between the hepatic cords; also there was minimal deposition of collagen fibers. Electron microscopic examination showed that most of the hepatocytes appeared normal. The results were discussed and it was concluded that taurine as well as folic acid protected the liver against damage but taurine was more effective in protecting against Mtx induced hepatic fibrosis. The use of folic acid remains controversial; there is controversy over the optimum dose of folic acid and over its effect on the therapeutic efficacy of Mtx. These results might enhance the use of taurine as a protective agent in Mtx induced hepatotoxicity. Hence, we recommend further studies on the hepatoprotective effect of taurine in chemically induced hepatic injury. |