Toxicity Of Prunus Africana And Its Effects On The Prostate Gland In Rats
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The present study reports on the acute and chronic toxic effects of Prunus africana in rats. The gross pathology, histopathology, haematological and biochemical findings are reported.Barks of old trees were collected, dried and reduced to a fine powder. One portion of the powder was extracted with boiling water and freeze dried (aqueous extract). Another portion was soxhlet extracted with chloroform and solvent removed (chloroform extract). The material remaining after chloroform extraction was re-extracted with methanol (methanol extract). The three extracts as well as the powdered bark were each administered to rats through various routes in order to study their effects in animals. a.)Toxicity of powdered bark Prunus africana bark (PAB) powder was fed to rats for 9 months "in a basal diet. Bodyweight gains occurred in groups fed 0-30% of the material. Deaths and weight loss occurred after 4-16 weeks in rats fed 50-70% of the powder respectively. Leucopaenia occurred in groups fed 50-70% of the material but not at 0-30% levels. Lymphocytolysis in all lymphoid organs, myocardial necrosis and mild vacuolation of hepatocytes occurred in groups fed 50-70% of the material. In addition, animals in these groups also showed gross reduction in size of prostate gland. This was associated with atrophy of glandular epithelium, decrease in acinar secretion and focal hyperplasia of glandular epithelium b) Determination of the LD50 of chloroform and aqueous extracts A 24-hour LD50 for chloroform and aqueous extracts of PAB was determined in rats after intraperitoneal administration. LD50 for chloroform and aqueous extracts was 2467 mg/kg and 850.5 mg/kg bodyweight respectively. Clinical responses in rats injected with fatal doses of aqueous extract were restlessness, raised hair coat, increased heart and respiratory rates, development of tucked up abdomen, hindleg weakness followed by depression and death. Fatal doses of chloroform extract caused rapid breathing, nervous signs such as repeated nodding movements characterized by banging of the head on the examination table, champing of the jaws, jerking of the limbs, circling and paralysis of the limbs. Hepatocellular and neuronal degeneration occurred in animals that were dosed with chloroform extract. Lymphocytolysis and myocardial haemorrhages occurred in those given aqueous extract. An acute/subacute to chronic study (3-6 months) after intraperitoneal administration of the fractions of LD50 of aqueous extract showed a graded dose response at 1/2, 1/4, 1/8 and 1/16 of the LD50. Pathological lesions namely myocardial degeneration and lymphocytic necrosis in lymphoid organs occurred at 1/2 and full LD50. Myocardial necrosis accompanied by histiocytosis and vascular lesions occured at 1/2 and 1/4 of the LDs () level and were thought to be of ischaemic origin. A granulomatous reaction occurred at the site of injection. c) Toxic effects of aqueous extract of PAD Effects of aqueous extract were monitored after daily treatment of groups of rats with logarithmically spaced oral doses (10 mg/kg to 1000 mg/kg bodyweight) for 8 weeks. Bodyweight increased in all groups. No deaths were recorded. Histopathological changes indicated mild hepatotoxicity and cardiotoxicity at 1000 mg/kg bodyweight but not at 10 mg/kg and 100 mg/kg bodyweight. Biochemical findings at 1000 mg/kg bodyweight.. indicated a significant increase in plasma alanine aminotransferase (ALAT), creatine kinase (CK) and a transient rise in lactate dehydrogenase (LDH). Aspartate aminotransferase (ASAT) and alkaline phosphatase (ALP) activity in plasma were within normal limits. These findings indicated that hepatotoxicity is mild after oral administration of this extract at high doses. Nephrotoxicity was absent on histopathology and blood urea nitrogen (BUN) was normal. Haematological parameters were within normal limits and the weight of prostate gland and other organs was unchanged at all dose levels. d) Toxic effects of chloroform extract of PAD pathological, haematological and biochemical changes were examined in rats that were orally treated with chloroform extract. Progressive weight gain was recorded e) Toxic effects of methanol extract of PAD. The effect of daily oral administration of logarithmically spaced doses 10 mg/kg, 100 mg/kg and 1000 mg/kg bodyweight of methanolic extract was monitored for 8 weeks. Progressive weight gain occurred in all groups.Haematological and biochemical parameters were within normal limits. Histopathological changes indicated mild cardiotoxicity at doses 100 mg/kg and 1000 mg/kg bodyweight, but no lesions occurred at 10 mg/kg bodyweight. A significant reduction in the weight of prostate gland occurred in animals treated with dose levels 10 mg/kg and 1000 mg/kg when compared to the controls. f) Effect of chloroform extract on prostate gland Variations in organ weight and organ-index (ratio of organ to final bodyweight) in the treatment groups were compared with those of the control animals. The extract caused a significant reduction in the weights of prostate gland but had no effect on the weight of seminal vesicles and testicles at doses between 0.1 mg/kg and 100 mg/kg bodyweight. statistical analysis indicated that the effective dose for reduction of prostatic weight in rats was 0.1 mg/kg to 1 mg/kg bodyweight. Further increases indose did not seem to alter the weight. Microscopical examination revealed atrophy of prostatic acinar epithelium, reduction in acinar secretion and focal hyperplasia of lining epithelium in treated groups. The effect of chloroform extract on prostate gland of young prepubertal rats was assessed in order to establish if the extract had an influence on the growth and development of the gland. This was an attempt to shed some light on the mechanism of action of the extract. Levels of serum acid phosphatase (ACP), notably the prostatic ACP were measured. On the basis of organ-index, there was a significant reduction in the weight of prostate gland at doses 10 and 100 mg/kg bodyweight against the control values after 8 weeks of treatment. seminal vesicular weight was not changed. A significant increase in total serum ACP and prostatic ACP above control values occurred at doses 10 mg/kg and 100 mg/kg bodyweight. From the results it was apparent that chloroform extract elevated prostatic ACP levels simultaneous with reduction in prostatic weight.