A-21 Day Safety Evaluation Of Methanol Extract Of Stem Bark of Artocarpus Altilis (Parkinson) Fosberg (Moraceae) in Wistar Rats

Background: Medicinal plants have been used as therapeutic agents since prehistoric era. Artocarpus altilis (Breadfruit) is used in African traditional medicine to treat hypertension with scanty information on its safety profile in animals.Objectives: This study was designed to evaluate the toxicological effects of oral administration of methanol extract of Artocarpus altilis (MEAA) in rats.Materials and Methods: Thirty male Wistar rats were divided into 6 groups of 5 animals each and were treated orally with corn oil (control), 100, 250, 500, 1000 and 2000 mg/kg of MEAA for twenty one days.Results: MEAA caused insignificant (p>0.05) changes in the activities of serum alanine and aspartate aminotransferases (ALT and AST) and alkaline phosphatase (ALP) relative to the control. Cardiac and hepatic AST (114.8±4.8 and (111.0±1.0) serum urea (1.1±0.2), creatinine (0.3±0.1), lactate dehydrogenase (17.3±5.8) and creatinine kinase (15.5±4.4) were significantly decreased (p<0.05) in rats treated with 2000 mg/kg of MEAA when compared to control [(134.8±5.8 and 129.7±5.0), 2.94±0.3, 0.4±0.1, 38.5±13.3 and 41.3±2.9]. The MEAA significantly decreased (p<0.05) serum total cholesterol and triglyceride while high density lipoprotein- cholesterol (HDL-c) level was increased. Histopathological examination of liver, kidney and aorta slides from MEAA- treated rats showed little alteration from the control.Conclusions: The MEAA could be safe when used over a long period for therapeutic purposes.Keywords: Artocarpus altilis, biochemical indices, lipid parameters, toxicity profile

Kolaviron, a biflavonoid complex from Garcinia kola seeds, ameliorates ethanol-induced reproductive toxicity in male wistar rats

In previous studies, we established that kolaviron (KV) (a biflavonoid from Garcinia kola seeds) elicited anti-oxidative and hepatoprotective effects in Wistar rats chronically treated with ethanol. The present study investigates the possible ameliorative effect of KV against ethanol-induced reproductive toxicity in male Wistar rats. Twenty-eight rats were randomly divided into four groups of seven animals each; Group 1 (control) was administered corn oil, group 2 was given 45%v/v ethanol at 3g/kg body weight, group 3 received ethanol and KV (200mg/kg) simultaneously and group 4 received KV alone. All drugs were given daily by oral gavage for 21 consecutive days. Ethanol treatment resulted in a significant (p<0.05) decrease in relative weight of testis of the animals. In the spermatozoa, ethanol intoxication resulted in 54%, 21% and 38% decreases in testicular protein content, sperm motility and count, respectively. In addition, ethanol administration enhanced lipid peroxidation (LPO) process assessed by the accumulation of malondialdehyde (MDA) in the testis. Precisely, MDA level was increased by 121% in the testis of ethanol-treated rats relative to the control. Furthermore, levels of testicular glutathione and activities of testicular antioxidant enzymes such as superoxide dismutase and catalase were significantly (p<0.05) reduced in ethanol-treated rats. Histopathology showed extensive degenerative changes in seminiferous tubules and defoliation of spermatocytes in testis of ethanol-treated rats. Interestingly, co-administration of KV with ethanol led to almost complete inhibition of testicular LPO thereby enhancing antioxidant status of the testis. Overall, KV ameliorates ethanol-induced toxic assault on testis and improves seminal qualities of the rats

Lipid-lowering effects of methanolic extract of Vernonia amygdalina leaves in rats fed on high cholesterol diet

Oluwatosin A Adaramoye, Olajumoke Akintayo, Jonah Achem, Michael A FafunsoDepartment of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, NigeriaAbstract: We investigated the lipid-lowering effects of methanolic extract of Vernonia amygdalina (VA) leaves in rats fed an high cholesterol diet, and compared with a standard hypolipidemic drug, Questran (Qu). The effects of VA on the lipid profile were assessed by measuring the levels of total cholesterol, triglyceride, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, lipid peroxidation (LPO), phospholipid, and glutathione (GSH) in the plasma and liver of the rats. Administration of cholesterol at a dose of 30 mg/0.3 ml, five times in a week for nine consecutive weeks resulted in a significant increase (p &lt; 0.05) in plasma and post mitochondrial fraction (PMF) cholesterol levels by 33% and 55%, respectively. However, treatment with extract of VA at doses of 100 and 200 mg/kg caused a dose dependent reduction in the plasma and PMF cholesterol by 20%, 23% and 23%, 29%, respectively. Similar reduction in cholesterol levels was obtained in Qu-treated rats. Furthermore, VA at 200 mg/kg decreased the plasma and PMF LDL-cholesterol levels by 23% and 49%, and also decreased plasma and PMF triglyceride levels by 29% and 28%, respectively. Also, VA at 100 and 200 mg/kg caused a dosedependent increase in plasma HDL-cholesterol levels by 41% and 59%, respectively. However, there were no significant differences (p &gt; 0.05) in the PMF HDL-cholesterol and phospholipid levels of the treated rats when compared to hypercholesterolemic rats. There were significant decreases (p &lt; 0.05) in the LPO levels of extract-treated rats. Precisely, VA at 100 and 200 mg/kg decreased the levels of plasma and PMF LPO by 38%, 42% and 35%, 45%, respectively. In addition, VA augmented the cholesterol-induced decrease in PMF glutathione levels of the rats. Taken together, these results suggest the lipid-lowering effects of VA and, probably serve as a new potential natural product for the treatment of hyperlipidemia.Keywords: hypercholesterolemia, lipid-lowering effect, Vernonia amygdalina, cholestero

Effect of chloroquine, methylene blue and artemether on red cell and hepatic antioxidant defence system in mice infected with Plasmodium yoelii nigeriensis.

Reactive oxygen species are mediators of tissue injury and are involved in malaria infection. In this study, the status of red cell and hepatic oxidative stress and antioxidant defence indices were investigated during Plasmodium yoelii nigeriensis (P. yoelii) infection, and treatment with chloroquine (CQ), methylene blue (MB) or artemether (ART) in mice. P. yoelii infection caused a significant (p 0.05) in the superoxide dismutase (SOD) activity of infected mice when compared to untreated normal. Treatment of infected mice with the three antimalarials showed that the drugs suppressed the parasitaemia in the order CQ > ART > MB. CQ, MB and ART treatment of infected mice caused a significant (p < 0.05) increase in the levels of hepatic GSH and GST. Specifically, CQ, MB and ART increased the levels of hepatic GSH by 108, 124 and 98 %, respectively, at day 6. Also, ART treatment of infected mice significantly (p < 0.05) elevated the red cell SOD level by 200 % at day 3. Taken together, the findings suggest that the antimalarial effect of CQ, MB and ART countered the P. yoelii-induced oxidative stress leading to the elevation of enzymatic and non-enzymatic antioxidants in the host system

Changes in antioxidant status and biochemical indices after acute administration of artemether, artemether-lumefantrine and halofantrine in rats.

Artemether, artemether-lumefantrine, or coartem and halofantrine are alternative antimalarial drugs to chloroquine. Their efficacy and potential to delay drug resistance in falciparum malaria had led to their increased use. Although these drugs have proven to be well tolerated, there are adverse effects associated with them. This study was designed to examine the toxic potential of acute administration of these drugs in rats. Twenty-four rats were divided into four groups: group I (control) received distilled water; group II received artemether for 5 days with an initial dose of 3.2 g/kg body weight on day 1 and 1.6 mg/kg body weight on days 2-5; group III received coartem (27 mg/kg body weight/day) for 3 days, which was divided into two equal portions per day; and group IV received halofantrine (24 mg/kg body weight/day) in three equal portions. Administration of artemether, coartem and halofantrine caused significant decrease (P 0.05) in the kidney glutathione levels. Furthermore, artemether, coartem and halofantrine decreased the liver- and kidney-enzymatic antioxidant status of the animals. Precisely, artemether, coartem and halofantrine decreased liver superoxide dismutase and catalase activities by 45%, 50% and 57%; and 20%, 29% and 23%, respectively. While the kidney catalase activities were decreased by 41%, 28% and 30%, respectively, the drugs however did not produce significant effect (P > 0.05) on the kidney superoxide dismutase activities. In addition, artemether, coartem and halofantrine decreased the hepatic levels of glutathione S-transferase by 64%, 51% and 53%, respectively. Administration of artemether, coartem and halofantrine significantly increased (P < 0.05) liver and kidney lipid peroxidation levels by 67%, 50% and 81%; and 58%, 43% and 31%, respectively. This indicates that the liver is considerably more affected than the kidneys. Similarly, halofantrine treatment caused significant elevation (P < 0.05) in the levels of serum creatinine, aspartate and alanine aminotransferases and blood urea nitrogen by 73%, 66%, 61% and 63%, respectively. These data indicate that oral administration of artemether, coartem and halofantrine has adverse effects on both enzymic and non-enzymatic antioxidant status of the animals

Antimalarial and antioxidant activities of methanolic extract of Nigella sativa seeds (black cumin) in mice infected with Plasmodium yoelli nigeriensis.

The antimalarial and antioxidant activities of methanolic extract of Nigella sativa seeds (MENS) were investigated against established malaria infection in vivo using Swiss albino mice. The antimalarial activity of the extract against Plasmodium yoelli nigeriensis (P. yoelli) was assessed using the Rane test procedure. Chloroquine (CQ)-treated group served as positive control. The extract, at a dose of 1.25 g/kg body weight significantly (p<0.05) suppressed P. yoelli infection in the mice by 94%, while CQ, the reference drug, produced 86% suppression when compared to the untreated group after the fifth day of treatment. P. yoelli infection caused a significant (p<0.05) increase in the levels of red cell and hepatic malondialdehyde (MDA), an index of lipid peroxidation (LPO) in the mice. Serum and hepatic LPO levels were increased by 71% and 113%, respectively, in the untreated infected mice. Furthermore, P. yoelli infection caused a significant (p<0.05) decrease in the activities of superoxide dismutase, catalase, glutathione-S-transferase and the level of reduced glutathione in tissues of the mice. Treatment with MENS significantly (p<0.05) attenuated the serum and hepatic MDA levels in P. yoelli-infected mice. In addition, MENS restored the activities of red cell antioxidant enzymes in the infected mice to near normal. Moreover, MENS was found to be more effective than CQ in parasite clearance and, in the restoration of altered biochemical indices by P. yoelli infection. These results suggest that N. sativa seeds have strong antioxidant property and, may be a good phytotherapeutic agent against Plasmodium infection in malaria