Traditional herbal medicine and their preparations have been widely used for thousands of years and are still in use in developing and developed countries owing to their medicinal values and their presumed relative safety. This belief that medicinal plants are not toxic or are with less side effect due to their natural origin is debatable; hence this study was conducted to evaluate the safety and (or) toxicity of Ethanol leaf extract of Simarouba glauca (EESG) on liver, kidney and heart functions of Wistar rats. The oral acute toxicity of EESG was evaluated in line with Lorke’s method. The sub-chronic toxicity of EESG was carried out according to the OECD guidelines with modification and using a total of twenty-four (24) male Wistar rats; divided into four groups of six rats each, following a two-week acclimatization. Test rats were orally administered EESG at doses of 500, 1000 and 2000 mg/kg body weight respectively daily for thirty (30) days, while the control was given only feed and water ad libitum. At the end of the experiment, the rats were fasted overnight and sacrificed under chloroform anesthesia; relevant biochemical and histopathology analyses were carried out. The data obtained from the oral acute test indicate that the LD50 was above 5000 mg/kg and there was no death recorded. There were significant increases (P ˂ 0.05) in percentage (%) body weight of rats administered respective doses of EESG. There were significant reductions (P˂0.05) in mean liver: body weight ratio of rats administered EESG 500 and 2000 mg/kg respectively, significant reductions (P˂0.05) in mean kidney: body weight ratios of rats given EESG 1000 and 2000 mg/kg respectively; significant reductions (P˂0.05) in mean heart: body weight ratios of test rats administered EESG 2000 mg/kg; whereas others were not significantly different (P˃0.05) relative to their respective control. Plasma ALT and GGT activities of rats administered respective dose of EESG were significantly reduced (P˂0.05); plasma ALP activities were significantly elevated (P˂0.05) relative to the control after 30 days. There were no significant differences (P˃0.05) in plasma total proteins and albumin levels. Plasma total and unconjugated bilirubin of rats administered respective dose of EESG were not significantly different (P˃0.05); whereas, rats given EESG recorded significant reduction in plasma conjugated bilirubin. Plasma urea was significantly elevated (P˂0.05) in rats administered EESG 1000 and 2000 mg/kg respectively. Test rats given EESG 500 and 1000 mg/kg respectively recorded significant elevations in plasma creatinine and rats given EESG 2000 mg/kg recorded significant decrease in plasma creatinine levels; others were not significantly different relative to the control. Plasma chloride and potassium ion levels of rats administered respective doses of EESG were not significantly different (P˃0.05); significant reduction (P˂0.05) in plasma sodium ions concentration in all group compared to the control. Plasma calcium ion levels in all group were not significantly different (P˃0.05); whereas there were significant reductions (P˂0.05) in plasma bicarbonate ion levels relative to their respective controls. Although plasma ALP activity were significantly elevated, there were no elevations in specific liver function enzymes and no visible hepatocellular damage. Furthermore, the conspicuous elevations observed in plasma urea and creatinine levels do not exclusively indicate EESG-induced organ injury. Therefore, it is suggestive that EESG was not significantly toxic to the to the liver, kidney and heart respectively and may be administered at lower doses in further studies.

Background Hypertension is a medical condition that often comorbidly exist in patients with type II diabetes. Therefore, it is very important to manage both conditions simultaneously to mitigate the complications and mortality connected with this comorbidity. Hence, this study investigated the antihypertensive and antihyperglycemic effects of combinations of losartan (LOS) with metformin (MET) and/or glibenclamide (GLB) in hypertensive diabetic rats. Hypertensive diabetic state was induced with desoxycorticosterone acetate (DOCA) and streptozotocin (STZ) in adult Wistar rats. The rats were divided into 5 groups (n = 5): control group (group 1), hypertensive diabetic (HD) control (group 2), treatment groups receiving LOS + MET (group 3), LOS + GLB (group 4), and LOS + MET + GLB (group 5). Group 1 comprised healthy rats while groups 2–5 were HD rats. The rats were treated orally once daily for 8 weeks. Fasted blood glucose (FBS) level, haemodynamic parameters, and some biochemical indices were thereafter assessed. Results FBS level and blood pressure measurements were significantly (P < 0.05) increased following induction by DOCA/STZ. The drug treatment combinations, particularly combination of LOS + MET + GLB, significantly (P < 0.05) reduced the induced hyperglycemia and remarkably decreased systolic blood pressure and heart rate. There was significant (P < 0.05) reduction in raised lactate dehydrogenase and creatinine kinase levels by all drug treatment combinations except LOS + GLB. Conclusions Our findings suggest that LOS combinations with MET and/or GLB exhibited significant antidiabetic and antihypertensive effects against DOCA/STZ-induced hypertensive diabetic state in rats.

Background and Purpose: Simarouba glauca is widely reported to contain a number of biologically active compounds with potentials in the treatment of numerous diseases. The study was conducted to evaluate the sub-acute effects of the aqueous leaf extract of Simarouba glauca (AESG) on lipoproteins and oxidative stress biomarkers in male Wistar rats. Methods: Oral administration of AESG was carried out in line with the guidelines of the Organization for Economic Co-operation and Development (OECD), No. 425 using a total of 24 male Wistar rats allotted to four groups (n=6); given distilled water, 500, 1000, and 2000 mg/kg/day of AESG respectively for 30 days. Results: In plasma, there was a significant reduction (P?0.05) in HDL-cholesterol; elevated (P?0.05) triglycerides (TG) at 1000 and 2000 mg/kg/day; elevated (P?0.05), and LDL-cholesterol at 500 and 1000 mg/kg/day, relative to the control. While the level of liver total cholesterol (TC) reduced significantly, it increased in the heart. Catalase (CAT) activity in the liver increased significantly (P?0.05) at all doses. The dose of 1000 mg/kg/day significantly (P?0.05) elevated kidney CAT activity. The activities of superoxide dismutase (SOD) in liver and heart reduced (P?0.05) at 500 mg/kg/day. At all doses, the levels of reduced glutathione (GSH) in plasma, liver and heart were comparable with the control. Although, there were no significant changes in plasma and liver glutathione peroxidase (GSH-PX) activity at all doses, animals given 500 mg/kg had reduction (P?0.05) in the heart GSH-PX activity compared to the control. Conclusion: Oral sub-acute AESG at high doses altered lipid homeostasis in plasma and heart without lipid peroxidation or oxidative stress. The extract has the potential to cause hyperlipidemia.