Adejuwon Adewale Adeneye

Protective effect of the aqueous leaf and seed extract of Phyllanthus amarus on gentamicin and acetaminophen-induced nephrotoxic rats.

AIM OF THE STUDY In African traditional medicine, different parts of Phyllanthus amarus Schum. and Thonn. (family: Euphorbiaceae) are highly valued for the treatment of array of human diseases including hepatic and urolithic and/or other renal diseases. In the present study, single oral 100-400mg/kg/day of the leaf and seed aqueous extract of Phyllanthus amarus (PA) were studied for their protective effects in acetaminophen- and gentamicin-induced nephrotoxic Wistar rats for 14 days. MATERIALS AND METHODS In each model of nephrotoxicities, thirty adult male Wistar rats were evenly divided into 5 groups. Groups I and II served as untreated and model controls, respectively while groups III-V were the treatment groups which were pretreated with 100-400mg/kg/day of PA 1hr before each dose of the nephrotoxicants for 14 days. On the 15th day, blood samples for serum urea and creatinine while the rat kidneys for histology were obtained under inhaled diethyl ether anesthesia. RESULTS In the acetaminophen nephrotoxic rats, 100-400mg/kg/day significantly (p<0.05, p<0.01, p<0.001) attenuated elevations in the serum creatinine and blood urea nitrogen levels in dose related fashion, as well as, attenuation of acetaminophen-induced tubulonephrosis. Similar effects were also recorded in the gentamicin model of acute renal injury. Results suggest that the nephroprotective effect of PA could be due to the inherent antioxidant and free-radical-scavanging principle(s) contained in the extract. CONCLUSIONS In the near future, PA could constitute a lead to discovery of a novel drug for the treatment of drug-induced nephrotoxicity.

Willingness to seek HIV testing and counseling among pregnant women attending antenatal clinics in Ogun State, Nigeria.

HIV counseling and testing (CT) is slowly being introduced as one of several key components of the comprehensive package of HIV/AIDS prevention and care in Nigeria, particularly in the prevention of mother-to-child transmission of HIV (PMTCT). Across-sectional survey of 804 women attending antenatal clinics (ANC) in Ogun State, Nigeria was done using questionnaires to assess their willingness to seek and undergo CT and know the determinants. Focus group discussions were also held in the general community: 84.3% of respondents believed in AIDS reality, while 24.3% thought they were at risk of HIV infection. Only 27% knew about MTCT, while 69.7% of 723 who had heard of HIV/AIDS did not know about CT. Only 71 (8.8%) had thought about CT and 33 (4.5%) mentioned HIV testing as one of antenatal tests. After health education on CT, 89% of the women expressed willingness to be tested. Their willingness for CT was positively associated with education (p < 0.05), ranging from 77% (no education) to 93% (post-secondary). More of those with self-perceived risk expressed willingness to test for HIV (p < 0.05). Those willing to be tested had a higher knowledge score on how HIV spreads than those not willing. Multiple regressions identified four key factors that were associated with willingness for CT: increasing educational level; not fearing a blood test; perception that the clinic offered privacy; and perceptions of higher levels of social support from relatives and peers. Those unwilling or undecided about CT expressed strong fear of social stigma/rejection if tested positive. The results provided insights for planning promotional programs and showed that not only are IEC efforts needed to boost knowledge about HIV/AIDS, but that change in clinic setting and community are imperative in creating supportive environment to encourage uptake of CT services.

The leaf and seed aqueous extract of Phyllanthus amarus improves insulin resistance diabetes in experimental animal studies

ETHNOPHARMACOLOGICAL RELEVANCE Amongst the Yoruba tribe (Southwest Nigeria), water decoction of the leaf and seed of Phyllanthus amarus Schum. and Thonn. is reputably used for the local management of diabetes mellitus, obesity and hyperlipidemia. AIM OF THE STUDY The present study seeks to evaluate the effectiveness and elucidate mechanism(s) of action of the aqueous leaf and seed extract of Phyllanthus amarus (PAE) in normal and 10% sucrose-induced hyperglycemia and dyslipidemia as an experimental model of insulin resistance diabetes mellitus. MATERIALS AND METHODS In this study, the repeated oral antihyperglycemic action of 150-600 mg/kg/day of PAE was evaluated in normal and 10% sucrose-induced insulin resistance rats using indicators such as fasting blood glucose (FBG), insulin and insulin resistance indices. The extracts weight losing, antihyperlipidemic and anti-atherogenic effects were also evaluated by measuring the effect of the extract on the body weight, plasma levels of triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c) and atherogenic indices. RESULTS In normal rats, PAE caused significant (p<0.05, p<0.01 and p<0.001) and dose related decreases in body weight, FBG, TG, TC, LDL-c, and atherogenic indices. Repeated oral treatment with 10% sucrose drink for 30 days was associated with significant (p<0.001) weight gain, hyperglycemia, insulin resistance indices, hyperlipidemia and atherogenic indices. However, pre-treatment with PAE significantly (p<0.05, p<0.01 and p<0.001) and dose-dependently attenuated increase in any of these measured parameters. CONCLUSIONS Overall, results of this study showed PAE to effectively control insulin resistance DM which was mediated via improvement in insulin resistance, thus, validating its ethnomedical use in the local management of DM.

Dose and time-dependent sub-chronic toxicity study of hydroethanolic leaf extract of Flabellaria paniculata Cav. (Malpighiaceae) in rodents

Flabellaria paniculata Cav. (Malpighiaceae) is a climbing shrub, the preparations of which are used in the treatment of wounds and ulcers in Nigeria and Ghana. This study investigated the sub-chronic toxicity profile of the hydroethanolic leaf extract of F. paniculata (HLE-FP). HLE-FP was administered p.o. (20, 100, and 500 mg/kg) for 30 and 60 days to different groups of rats. Control animals received 10 ml/kg distilled water. In the group of animals for reversibility study, HLE-FP administration ceased on the 60th day and animals were monitored for a further 15 days. Results showed that oral treatment with HLE-FP for 30 days caused significant (p < 0.05) reductions in weight gain pattern compared to control. These changes were sustained with 60 days treatment. However, no significant (p > 0.05) differences in relative organ weights between control and treatment groups were observed. HLE-FP-treated rats showed significant (p < 0.05) increases in Hb, PCV and RBC on day 30 and significant (p < 0.05) increases in MCV and MCH indices on day 60 compared to control. There were significant (p < 0.05) elevations in serum K+, urea and creatinine compared to control. The liver function tests showed slight but non-significant alterations in relevant parameters when compared to control. Biochemical findings were supported by histopathological observations of vital organs including the kidney and liver. Toxicities observed in respect of kidney function were irreversible at 15 days of stoppage of treatment. In the acute toxicity study, HLE-FP given p.o. caused no lethality at 5000 mg/kg but behavioral manifestations like restlessness, generalized body tremor, feed, and water refusal were observed. The i.p. LD50 was estimated to be 2951.2 mg/kg. Findings in this study showed that HLE-FP is relatively non-toxic on acute exposure and generally safe on sub-chronic administration, but could be deleterious on the kidneys on prolonged oral exposure at a high dose. Thus, caution should be exercised with its long-term usage.

Hypoglycaemic effect of Ipomoea batatas aqueous leaf and stem extract in normal and streptozotocin-induced hyperglycaemic rats

Background: Among the Yoruba herbalists (South-west Nigeria), hot water infusion of the whole plant of Ipomoea batatas continues to be highly valued in the local management of diabetes because of its effectiveness in the control of blood glucose. Therefore, the present study investigates the blood glucose lowering effect of graded oral doses of the extract in normal and streptozotocin (STZ)-induced diabetic rats as a way of validating its folkloric use in the local management of diabetes mellitus. Materials and Methods: 100, 200 and 400 mg/kg/day of the aqueous whole plant extract of Ipomoea batatas (IB) were administered to normal and STZ-induced hyperglycemic rats as single, daily oral treatment for 14 days and their effects on the fasting blood glucose (FBG) was evaluated. In addition, the acute oral toxicity and preliminary phytochemical studies of IB were also conducted. Results: These showed that oral administration of IB for 14 days caused signifi cant dose related reductions (P<0.05, P<0.001) in FBG of both normal and STZinduced hyperglycemic rats. Oral treatment with 400 mg/kg/day IB also signifi cantly attenuated (P<0.05) body weight gain in the treated rats. The oral LD 50 for IB was estimated to be 12 g/kg while the phytochemical analysis of the extract showed the presence of alkaloids, fl avonoids, tannins, saponin, anthraquinones and reducing sugars in the extract. Conclusions: The data generated in this study validate the folkloric use of the hot infusion of the whole plant of IB in the local management of diabetes.

Knowledge and perception of HIV/AIDS among pregnant women attending antenatal clinics in Ogun State, Nigeria

Mother-to-child transmission of HIV (MTCT) is responsible for more than 90% of the cases of HIV infection in infants and children in sub-Saharan Africa. Accurate data on the knowledge and perceptions of HIV/AIDS among women attending antenatal clinics in Nigeria are scarce. A cross-sectional survey of 804 women attending antenatal clinics in Ogun State, South-West Nigeria was done using interviewer-administered questionnaires. Approximately 90% of the women respondents had heard of HIV/AIDS, but only about 27% knew HIV could be transmitted from mother to child; of those, almost 94% believed in the reality of HIV disease; in contrast, the majority (64%) believed they were not at risk of HIV infection, and a slightly greater proportion (70%) did not understand the benefits of voluntary HIV counselling and testing (VCT). Nonetheless, almost 90% of respondents were willing to know their status following health education about VCT. Those that were older, attending public hospitals, and with a higher level of education had more knowledge and better perceptions about HIV. The results suggest an urgent need for public health education on HIV/AIDS and the benefits of VCT to control MTCT, particularly targeting young women and those with little or no education.

Modulatory potentials of the aqueous stem bark extract of Mangifera indica on carbon tetrachloride-induced hepatotoxicity in rats

Among Yoruba herbalists (Southwest Nigeria), hot water infusion of Mangifera indica L. (芒果 Máng Guǒ) stem bark is reputedly used for the treatment of fever, jaundice and liver disorders. The present study, therefore, investigates the protective effects and mechanism(s) of chemopreventive and curative effects of 125–500 mg/kg/day of Mangifera indica aqueous stem bark extract (MIASE) in acute CCl4-induced liver damage in rats. Rats were treated intragastrically with 125, 250 and 500 mg/kg/day of MIASE for 7 days before and after the administration of CCl4 (3 ml/kg of 20% CCl4, i.p.). The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c), total bilirubin (TB), conjugated bilirubin (CB) and fasting blood glucose (FBG) levels were estimated. In addition, hepatic tissue reduced glutathione (GSH) and the malondialdehyde (MDA) concentrations, catalase (CAT), superoxide (SOD) activities in the hepatic homogenate, and histopathological changes in the rat liver sections were determined. Preliminary qualitative phytochemical screening for bioactive compounds in MIASE was also conducted. Results showed that oral treatment with 125–500 mg/kg/day of MIASE significantly attenuated the increase in serum ALT, AST, ALP, FBG, TB, CB and LDL-c levels in acute liver injury induced by CCl4 treatment. Findings also revealed significant elevations in the serum TC, TG, HDL-c, TP and ALB levels. There was marked architectural remodeling in the hepatic lesions of hepatocyte vacuolation and centrilobular necrosis induced by CCl4 treatment, coupled with significant weight loss. MIASE also markedly enhanced SOD and CAT activities while reducing MAD formation; and increased GSH concentration in the hepatic homogenate compared with untreated CCl4-intoxicated group, with more protection offered in the curative than the chemopreventive models of CCl4 hepatotoxicity. Thus, these results indicate that MIASE has a profound protective effect against acute CCl4-induced hepatotoxicity in rats, which may be due to its free radicals scavenging effect, inhibition of lipid peroxidation, and its ability to increase antioxidant activity.

Modulatory effect of Mangifera indica against carbon tetrachloride induced kidney damage in rats.

Abstract 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.

Subchronic and Chronic Toxicities of African Medicinal Plants

Herbal medicine provides for about 30% of health care needs of many rural populations globally, suggesting its pivotal role in the health care and pharmaceutical industries. One of the drawbacks associated with drug discovery and development is toxicity, which results from exposures to both natural plant-derived and man-made drugs. It is a common belief and claim among traditional herbal practitioners and herbal product consumers that herbal products are free of toxicities. However, recent and emerging evidence-based research findings are refuting these folkloric claims with preclinical and clinical evidence of toxicities being presented to back up the counter-claims. Thus, this chapter aims to review and highlight subchronic and chronic oral toxicity profiles of a few selected commonly used medicinal plants from the different African folkloric medicines, with the view of providing scientific data on their documented toxicity profiles which may serve as ethnobotanical pharmacovigilance guide to their use.

Protective effect of selected calcium channel blockers and prednisolone, a phospholipase-A2 inhibitor, against gentamicin and carbon tetrachloride-induced nephrotoxicity.

The ameliorative effect of calcium channel blockers (CCBs) and a phospholipase-A2 inhibitor in drug-/chemical-induced nephrotoxicity was investigated. Rats were divided into 7 groups of 5 rats in each group. In the gentamicin model, group I rats were pretreated with normal saline (10 ml kg−1), while groups II–VII rats were pretreated with normal saline (10 ml kg−1), ascorbic acid (10 mg kg−1), nifedipine (0.86 mg kg−1), verapamil (4.3 mg kg−1), diltiazem (3.43 mg kg−1), and prednisolone (0.57 mg kg−1), respectively, perorally 1 h before intraperitoneal (i.p.) injection of gentamicin (40 mg kg−1) for 14 days. In the carbon tetrachloride (CCl4) model, rats were pretreated with CCBs and prednisolone for 7 days before inducing nephrotoxicity with 20% CCl4 (1.5 ml kg−1). Rats were thereafter killed and blood and tissue samples were collected for assessments. I.p. injections of gentamicin and CCl4 caused significant hypernatremia, hypokalemia, hypocalcemia, hypophosphatemia, and hyperchloremic alkalosis and reduced renal tissue levels of antioxidants. Also, significant reductions in the hemoglobin, packed cell volume, red blood cells, and platelet indices were observed. Pretreatments with nifedipine (0.86 mg kg−1), verapamil (4.3 mg kg−1), diltiazem (3.43 mg kg−1), and prednisolone (0.57 mg kg−1) significantly ameliorated the deleterious effects of gentamicin and CCl4 possibly via antioxidant and anti-lipoperoxidation mechanisms. The results obtained in this study suggest potential clinical usefulness of tested CCBs and prednisolone in drug-/chemical-induced nephrotoxicity.