Protective effect of carvedilol alone and coadministered with diltiazem and prednisolone on doxorubicin and 5-fluorouracil-induced hepatotoxicity and nephrotoxicity in rats.

This study investigated the protective effects of carvedilol alone and coadministered with prednisolone and diltiazem on doxorubicin (DOX) and 5-fluorouracil (5-FU)-induced toxicity. Each of 2 pools of 70 female rats were randomly allotted into 10 groups of 7 animals each and treated as follows: Group 1: normal saline (10 mL/kg); Group 2: normal saline and DOX (40 mg/kg)/5-FU (20 mg/kg) alone; Group 3: gallic acid (200 mg/kg) and DOX/5-FU; Group 4: carvedilol (0.075 mg/kg) and DOX/5-FU; Group 5: carvedilol (0.15 mg/kg) and DOX/5-FU; Group 6: carvedilol (0.30 mg/kg) and DOX/5-FU; Group 7: diltiazem (3.43 mg/kg) and DOX/5-FU; Group 8: diltiazem (3.43 mg/kg), carvedilol (0.15 mg/kg), and DOX/5-FU; Group 9: prednisolone (0.57 mg/kg) and DOX/5-FU; and Group 10: prednisolone (0.57 mg/kg), carvedilol (0.15 mg/kg), and DOX/5-FU. Treatments were done p.o. for 16/14 days for the DOX/5-FU models. DOX/5-FU was administered i.p. to the rats in Groups 2-10 on day 14/10-14. On day 17/15 (DOX/5-FU), blood samples were collected, and liver and kidneys of rats were harvested for antioxidant and histopathological assessments. Carvedilol alone and coadministered with prednisolone significantly (P < .05) decreased alanine aminotransferase level compared with administration of DOX alone. Carvedilol alone and coadministered with diltiazem significantly (P < .05) decreased creatinine level compared with administration of DOX/5-FU alone. Carvedilol alone and coadministered with diltiazem and prednisolone significantly (P < .05) increased the level of hepatic superoxide dismutase and catalase, and decreased malondialdehyde compared with DOX administration alone. Histopathological observations correlated with results of biochemical and antioxidant analyses. Carvedilol administered alone and coadministered with diltiazem and prednisolone reduced the effect of DOX/5-FU-induced hepatic and renal toxicities due to enhanced in vivo antioxidant activity. The protective effect was more prominent in the doxorubicin model compared with the 5-fluorouracil test. Coadministration of carvedilol with either diltiazem or prednisolone did not show better protection relative to carvedilol alone.

Sub-Chronic Toxicity of the Hydroethanolic Leaf Extract of Telfairia occidentalis Hook. f. (Cucurbitaceae) in Male Rats.

Background: Due to its nutritional and medicinal values, the leaf of Telfairia occidentalis Hook f. (Cucurbitaceae) is consumed in different parts of Nigeria. Acute and sub-chronic toxicity of the hydroethanolic leaf extract of Telfairiaoccidentalis were investigated in this study. Methods: Sixty-four male rats were randomized into four different groups of 16 animals each and were separately administered 80, 400 and 2000 mg/kg T. occidentalis orally (p.o.) for 60 days. Animals were sacrificed and blood samples were collected for hematological and biochemical analyses. Vital organs were harvested and evaluated for in vivo antioxidants and histopathological changes. Results: A significant (p < 0.05) reduction in weight of the testes, compared to the control group, was observed in the group treated with 2000 mg/kg extract. No significant change was observed in the weight of other vital organs relative to the control group. There were significant (p < 0.01) increases in sperm motility and count in the group administered 80 mg/kg extract and significant (p < 0.001) reductions in both parameters at 2000 mg/kg. There were significant increases in the levels of hemoglobin and packed cell volume at 80 and 2000 mg/kg of the extract. In respect of liver function parameters, significant reductions in aspartate aminotransferase and alanine aminotransferase levels at doses of 400 and 2000 mg/kg relative to control were observed. Compared to control, the extract significantly reduced (p < 0.05) the level of total cholesterol (400 mg/kg) and caused a significant increase in the level of high-density lipoprotein (80, 400 and 2000 mg/kg). Significant (p < 0.05) increase in the level of malondialdehyde, decrease in superoxide dismutase level and histopathological abnormalities were observed in the testes at 2000 mg/kg. Upon cessation of treatment with T. occidentalis for 30 days, the observed effects were reversed. Conclusions: The findings showed that the hydroethanolic leaf extract of Telfairia occidentalis is relatively non-toxic on acute and sub-chronic exposures at low to moderate doses, with the potential to elicit anti-anemic effects, reduce the risk of atherosclerosis and cardiovascular disease, and enhance antioxidant status in the brain and liver. Although possibly beneficial at low to moderate doses, the extract could be harmful to the testes with prolonged oral exposure at high dose.

90 Days toxicological assessment of hydroethanolic leaf extract of Ipomoea asarifolia (Desr.) Roem. and Schult. (Convolvulaceae) in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ipomoea asarifolia (Convolvulacae), commonly known as "morning glory" is found across West Africa. Preparations of the plant are used traditionally for the treatment of diverse ailments including diabetes, neuralgia, arthritic pain and stomach ache. This study was designed to assess the safety profile of the hydroethanolic leaf extract of I. asarifolia through a 90-day subchronic toxicity study in rats. MATERIALS AND METHODS: I. asarifolia was administered p.o. at doses of 40, 200 and 1000mg/kg to separate groups of rats for 90 days. Distilled water was given p.o. to rats in the control group. Some set of rats in each group were left for additional 30 days without administration of the extract for reversibility study. Animals were weighed weekly and relevant parameters were assayed at the end of the main and reversibility study periods. RESULTS: There was no significant change (p>0.05) in the body weight of rats, and food and water intake in I. asarifolia treated groups compared with control. I. asarifolia (40-1000 mg/kg) significantly but reversibly reduced (p<0.05, 0.001) sperm motility and count. The extract did not generally cause significant change (p>0.05) in the weight of vital organs and haematological parameters except in the case of reversible reduction in the level of haemoglobin and red blood cell count (p<0.01; 40 mg/kg). The level of biochemical parameters and electrolytes were not significantly changed (p>0.05) except for the reversible reduction in the level of aspartate aminotransferase (AST; p<0.0001; 200 and 1000 mg/kg) and increase in the level of Na(+) (p<0.01; 200 mg/kg). The level of kidney reduced glutathione (GSH) was reversibly increased (p<0.01; 1000 mg/kg) while the level of enzymatic and non-enzymatic in vivo antioxidants was generally comparable and not significantly different (p>0.05) from control in respect of all other vital organs. Histological presentations were generally normal in respect of the liver, kidneys, brain, heart, lungs, pancreas, spleen and testes. CONCLUSIONS: The findings in this study suggest that the hydroethanolic leaf extract of I. asarifolia is relatively safe administered orally for an extended period with potential renal in vivo antioxidant activities. However, the extract may cause reversible male sterility, anaemia and hypernatraemia.