HIV/AIDS related mortality has been dramatically reduced by the advent of antiretroviral therapy (ART). However, ART presents with associated adverse effects. One of such adverse effects is hepatotoxicity observed with nevirapine (NVP) containing ART. Since previous studies showed that NVP hepatotoxicity may be due to oxidative stress via generation of oxidative radicals, this study sought to evaluate the protective effects of antioxidants in alleviating NVP induced hepatotoxicity. Rats were divided into 6 groups with 8 animals per group and received doses of the antioxidants jobelyn (10.7 mg/kg/day), vitamin C (8 mg/kg/day), vitamin E (5 mg/kg/day) and/or NVP (6 mg/kg/day) for 60 days. The animals were sacrificed on day 61 by cervical dislocation, blood samples were collected for biochemical and hematological examination. The liver of the sacrificed animals was weighed and subjected to histopathological examination. There was a statistically significant (p<0.05) elevation in MDA level observed in the NVP group as compared with control. The results further showed non-significant decreases in the levels of MDA in the NVP plus antioxidant groups, except vitamin C, when compared with the NVP alone group. Vitamin E and Vitamin E plus C treated groups showed significantly (p<0.05) higher levels of SOD, CAT and GSH. The results also showed statistically significantly (p<0.05) lower levels of ALT and AST in the antioxidant treated groups There was an observed significantly (p<0.05) higher level of TP and urea in the antioxidant treated rats. A significantly (p<0.05) higher white blood cell count was observed in the antioxidant groups. Histopathological assessment of the liver extracted from the rats showed no visible pathology across the groups. Observations from this study suggest a potentially positive modulatory effect of antioxidants and may be indicative for the inclusion of antioxidants in nevirapine containing ART.
Bridelia ferruginea is a woody shrub that grows in the Savannah or rain forests of Africa and has traditionally been used to treat diabetes, arthritis and boils. Despite all these uses, extensive toxicological evaluation has not been carried out. The aim of the present investigation was to evaluate the sub-chronic toxicological effects of the stem bark aqueous extract of Bridelia ferruginea in rats. The lethal dose (LD50) was determined using probit analysis and graded doses of the extract (250–4 000 mg/kg) were administered to the animals via oral and intraperitoneal routes and observed for mortality, behavioral changes and signs of toxicity. Sub-chronic toxicity study was carried out at doses of 1 000, 2 000 and 4 000 mg/kg administered daily for 60 days. The animals were sacrificed after 60 days. Blood was collected for biochemical (renal and hepatic), hematological, oxidative stress, sperm and histopathological examinations, using standard methods. LD50 of the extract was estimated as >4 000 mg/kg orally; neither significant visible signs of toxicity nor mortality were observed. There were no significant differences in the animals and organ weights, hematological and biochemical parameters in the treated groups compared to the control group. However, a significant increase (p<0.05) in the level of lipid peroxidation and a significant (p<0.05) decrease in sperm count were observed in the treated animals compared with the control group. The stem-bark aqueous extract of Bridelia ferruginea was found to be relatively safe, though it has the potential to cause lipid peroxidation and damage sperm quality and should thus be used with caution.
There is little scientific evidence on the local use of Mangifera indica in kidney diseases. This study investigated the reno-modulatory roles of the aqueous stem bark extract of Mangifera indica (MIASE) against CCl4-induced renal damage. Rats were treated intragastrically with 125, 250 and 500 mg/kg/day MIASE for 7 days before and after the administration of CCl4 (3 ml/kg of 30% CCl4, i.p.). Serum levels of electrolytes (Na+, K+, Cl−, HCO3−), urea and creatinine were determined. Renal tissue reduced glutathione (GSH), malondialdehyde (MDA), catalase (CAT), superoxide (SOD) activities were also assessed. The histopathological changes in kidneys were determined using standard methods. In CCl4 treated rats the results showed significant (p<0.05) increases in serum Na+, K+, Cl−, urea and creatinine. CCl4 also caused significant (p<0.05) decreases in renal tissue SOD, CAT and GSH and significant (p<0.05) increases in MDA. The oral MIASE treatment (125–500 mg/kg) was found to significantly (p<0.05) attenuate the increase in serum electrolytes, urea and creatinine. Similarly, MIASE significantly (p<0.05) attenuated the decrease in SOD, CAT and GSH levels and correspondingly attenuated increases in MAD. Mangifera indica may present a great prospect for drug development in the management of kidney disease with lipid peroxidation as its etiology.
Background: Mangifera indica (Anacardiaceae) is an important herb in the traditional African and Ayurvedic medicines. The stem barks are used in the treatment of hypertension, insomnia, tumour, depression, rheumatism and as a tonic. This study was carried out to investigate antidepressant- and anxiolytic-like effect of the hydroethanol stem bark extract of M. indica (HeMI) in mice.
Methods: HeMI (12.5–100 mg/kg, p.o.) was administered 1 h before subjecting the animal to the forced swim test (FST), tail suspension test (TST) and elevated plus maze tests (EPM).
Results: HeMI (12.5–100 mg/kg, p.o.) treatment produced significant reduction in immobility time [F(6.56)=8.35, p<0.001], [F(6,56)=7.55, p<0.001] in the FST and TST, respectively. Moreover, co-administration of sub-therapeutic doses of imipramine or fluoxetine with HeMI (3.125 mg/kg) elicited significant reduction in time spent immobile in the FST. However, pretreatment of mice with parachlorophenylalanine, metergoline, yohimbine or sulpiride abolished the antidepressant-like effect elicited by HeMI. In the EPM, HeMI produced significant [F(5,42)=8.91, p<0.001] increase in open arms exploration by 75.55 % and this effect was blocked by pretreatment of mice with flumazenil or metergoline.
Conclusions: Findings from this study showed antidepressant-like effect of M. indica through interaction with 5-HT2 receptor, α2-adrenoceptor and dopamine D2-receptors. Also, an anxiolytic-like effect through its affinity for 5-HT2 and benzodiazepine receptors. Hence, M. indica could be a potential phytotherapeutic agent in the treatment of mixed anxiety-depressive illness.
Background:Annona muricata Linn. (Annonaceae) (AM) fruit juice is widely consumed either raw or after processing in tropical countries because of its very juicy, creamy and sweet character including its medicinal importance. The safety of AM fruit was investigated in Sprague-Dawley rats for acute and 60-day subchronic toxicity effects.
Methods: Rats were administered distilled water (DW) and AM daily at doses of 80, 400 and 2000 mg/kg orally for 60 days. At the end of the study, blood samples were assayed for biochemical and hematological parameters. Vital organs were harvested and assessed for antioxidants and histopathology.
Results: There was no mortality recorded up to 2000 mg/kg following acute administration. There were no significant changes in vital organ weights and hematological and biochemical parameters. However, significant (p<0.05) reduction in platelet count and packed cell volume was observed at 2000 and 400 mg/kg, respectively, which was reversed after cessation of treatment. Interestingly, subchronic oral administration of AM (80, 400 or 2000 mg/kg) significantly (p<0.001) increased sperm count and motility in comparison to vehicle-treated control. AM long-term treatment induced significant (p<0.05, <0.01 and <0.001) increases in the levels of glutathione, superoxide dismutase (SOD) and catalase, respectively, in the liver and kidney. Conversely, AM (2000 mg/kg) produced significant (p<0.001) increase in malondialdehyde level with decreased (p<0.05) SOD activity in the brain.
Conclusions: The study established that AM did not induce any significant toxic effect, indicating that it is safe in rats following oral administration for 60 consecutive days.
Background: Strophanthus hispidus DC (Apocynaceae) is a medicinal plant widely used in traditional African medicine in the treatment of rheumatic afflictions, ulcer, conjunctivitis, leprosy and skin diseases. This study sought to investigate the antinociceptive, anti-inflammatory and antiulcer properties of the ethanol root extract of S. hispidus.
Methods: Antinociceptive activity was evaluated using acetic acid-induced writhing and formalin tests in mice. The carrageenan- and egg albumin-induced rat paw edema tests were used to investigate the anti-inflammatory actions, whereas the antiulcer activity was investigated using ethanol-, HCl- and pyloric ligation-induced gastric ulcer models in rats.
Results: S. hispidus [100–800 mg/kg orally (po)] produced significant (p<0.05) inhibition of writhing reflex with peak effect of 74.13% inhibition observed at 800 mg/kg. Similarly, S. hispidus significantly (p<0.05) attenuated formalin-induced early and late phase of nociception with peak effect of 61.84% and 89.43%, respectively, at 200 mg/kg. S. hispidus (25–800 mg/kg po) caused significant (p<0.05) inhibition of edema development in the carrageenan and egg albumin models with peak effect (93.40% and 90.10% inhibition of edema formation) observed at 50 mg/kg. With respect to antiulcer activity, S. hispidus (100–800 mg/kg) showed potent antiulcer activity with respective peak effects of 96% (ethanol-induced), 99% (HCl-induced) and 70.60% inhibition of ulcer.
Conclusions: The findings in this study suggest that the ethanol root extract of S. hispidus possesses antinociceptive, anti-inflammatory and antiulcerogenic activities. This justifies the use of the extract in folklore medicine for the treatment of ulcer and inflammatory disorders.
Garcinia kola (GK) stem bark, Uvaria chamae (UC) root, and Olax subscorpioidea (OS) root are components of various indigenous/traditional anticancer regimens. It is, therefore, possible that they might combat oxidative stress and impair cellular proliferation linked to carcinogenesis. In this study, we investigated the antioxidative, mito-depressive, and DNA-damaging activities of the three plant extracts in order to provide further mechanistic insights into their potential anticancer roles in documented cancer remedies that include them. Antioxidative properties were investigated in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and nitric oxide (NO) radical scavenging assays and an animal model of drug (cisplatin)-induced oxidative stress. The Allium cepa assay and the single cell gel electrophoresis (SCGE) assay were used to assess mito-depressive and DNA-damaging activities. GK and OS showed significantly higher antioxidant activities in the DPPH assay than ascorbic acid; OS had the lowest IC50 of the three plants in the NO assay, comparable to that of ascorbic acid. Pretreatment with the extracts produced an ameliorative and protective effect against the cisplatin-induced oxidative stress as shown by inhibition of lipid peroxidation and improved or restored reduced glutathione and superoxide dismutase levels. In the Allium test, the three extracts produced significant decreases in root growth and also significant cytotoxicity as evidenced by decreased mitotic index. Each of the extracts also showed significantly increased tail DNA (%) in the SCGE assay, indicating the significant DNA-damaging effect. Taken together, this study demonstrates the possible chemopreventive and chemotherapeutic potentials of the three study extracts, which may explain the roles of their source plants in traditional remedies in the therapy of cancers.