Effects of Morinda citrifolia on N-methyl N-nitrosourea-induced peripheral T cell non-Hodgkin's lymphoma in Sprague Dawley rats

N-methyl N-nitrosourea (MNU) is a carcinogen that had been reported to be able to cause malignant lymphoma and/or leukemia to the lympho-hematopoietic system. Morinda citrifolia is a known anti-tumor medicinal herb. The present study was conducted to investigate the ability of MNU to induce T cell non-Hodgkin’s lymphoma in male Sprague Dawley rats and to investigate the anti-tumor effects of Morinda citrifolia on affected rats. Sixty four 8 weeks old male Sprague Dawley rats were divided into four groups of sixteen rats in each group. Groups B (MNU treated) and D (Morinda citrifolia and MNU treated) rats received four consecutive intraperitoneal injections of MNU at a dose of 60 mg/kg body weight, while groups A and C rats received four consecutive intraperitoneal injections of normal saline. Groups C and D rats were fed daily with a ration mixed with Morinda citrifolia fruit powder at a dose of 750 mg/kg body weight.Groups A and B rats were fed with Morinda citrifolia-free ration. The rats were sacrificed after 20 weeks of experimental period by bleeding following xylazine and ketamine anaesthesia. Complete gross examination and weighing of the organs were conducted. Samples of the lymph nodes, spleen, liver, lung, kidneys, heart, thymus, stomach, large intestine and small intestine were collected for histopathology and immunohistochemistry. The peripheral blood was collected for haematology and blood biochemistry. Lymph nodes enlargement was observed in five rats (32%) of group B and one rat (6%) of group D. Hepatomegaly and splenomegaly were observed in four rats (25%) of group B and one rat (6%) of group D. Enlargement of kidneys was observed in two rats (12%) of group B. Histopathology revealed lymphoma in the enlarged organs and in the lungs, kidneys and heart of groups B and D rats. The lymphoma lesions were characterized by the proliferation and/or infiltration of undifferentiated, small to medium, bizzare pleomorphic neoplastic lymphocytes with evidence of mitosis in the lymph nodes, spleen, liver, lungs, kidneys and heart of groups B and D rats. However, the thymus, stomach, large intestine and small intestine appeared normal. Groups A and C rats showed normal histology in all organs. The statistical analysis of lesion scoring results of lymphoma lesions showed significant (p<0.05) differences in the lymph nodes, spleen, liver, lungs and kidneys of group B rats compared with rats in other groups. The neoplastic lymphocytes in affected organs showed positive expression to T cell marker (CD3) and negative expression to B cell marker (CD79α) which confirmed that the lymphoma which was observed is T cell non-Hodgkin’s lymphoma.Lymphatic leukemia was observed in groups B and D rats where severe lymphocytosis was observed in four rats (28%) of group B and one rat (6%) of group D. The RBC and HGB count results showed anemia in seven rats (50%) of group B and two rats (18%) of group D and the manually counted packed cell volume results showed anemia in four rats (28%) of group B and two rats (18%) of group D. Groups A and C rats did not show any abnormal blood parameters. The blood biochemical results showed significant (p<0.05) increased in aspartate transaminase (AST), alanine transaminase (ALT), bilirubin, urea and creatinine levels in group B rats and the uric acid levels also significantly (p<0.05) increased in group B rats and group D rats. The lactate dehydrogenase (LDH) levels decreased in group B and group D rats. Group C rats did not show any blood biochemistry changes in the serum parameter levels. Therefore, it can be concluded that the gross pathology, histopathology, immunohistochemistry and blood biochemistry analyses revealed that the MNU can induce T cell non-Hodgkin’s lymphoma in male Sprague Dawley rats. Haematology results showed that the MNU can also induced lymphatic leukemia accompanied with anemia in the male Sprague Dawley rats. This study also showed that the Morinda citrifolia fruit powder at a daily dose of 750 mg/kg body weight had the ability to reduce the peripheral T cell non-Hodgkin’s lymphoma, lymphatic leukemia and anemia induced by MNU in the male Sprague rats.

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