Subacute and subchronic oral toxicity assessments of Acridocarpus smeathmannii (DC.) Guill. & Perr. root in Wistar rats.

Recent adverse herb reactions have stimulated interest documenting the safety profile of medicinal agents. Thus, subacute and subchronic oral toxicity of the hydroethanolic extract of Acridocarpus smeathmannii root (HEASR) in Wistar rats was investigated. In the 28 and 90-day subacute and subchronic toxicity tests, sixty-four rats (n = male: female = 1:1 = 32) were divided into four of eight/group and ninety-six (n = male: female = 1:1 = 48) into twelve/group respectively. Distilled water (10 mL/kg) or HEASR4, HEASR5 and HEASR6 (250, 500 and 1000 mg/kg/day) respectively were administered via oral gavage. Animals were killed humanely 24 h after the last administration. Using standard methods, acute oral toxicity dose of HEAR (2000 mg/kg) was non-lethal in rodents. Subacute administration of HEASR6 increased total bilirubin (p < 0.05) in female rats. HEASR moderately altered both haematological and biochemical indices in rats. HEASR6 administration reduced ovary weight in both studies while follicle stimulating hormone level in male was reduced at all doses used. HEASR modulated lipid peroxidation, sperm quality and elevated cyclooxygenase-2 levels in rats. Histology revealed gastritis and congestions in vital organs. The low-observed adverse effect level for HEASR was below 250 mg/kg for both sexes. Overall, HEASR demonstrated inherent toxicity evidenced by our current findings. The exaggeration of its folklore medicine applications calls for cautions.

In vivo Safety Evaluation of a Nigerian Polyherbal Mixture in Female Wistar Rats.

The present study evaluates the oral safety and oral toxicity reversibility of a Nigerian Polyherbal Mixture (NPM) in female Wistar rats. In this study, acute oral toxicity was conducted on 20 female Wistar rats using the limit dose test of Up-And-Down Procedure of the OECD Acute Oral Toxicity Testing 425 guidelines at 5000 mg/kg of NPM. Additionally, 40 female Wistar rats (120-150 g) were divided into 4 groups (n=10) and orally treated with 10ml/kg of distilled water, 82 mg/kg, 410 mg/kg and 2050 mg/kg of NPM, respectively, for 90 days. Five rats from each group were sacrificed while the remaining rats in each group were kept for another 14 days for oral toxicities reversibility test. Blood samples and vital organs were obtained for biochemical, hematological and histological changes. Results showed that acute oral toxicity testing of NPM caused no death in any of the three sequentially treated rats and its estimated LD50 value was greater than 5000 mg/kg. Chronic oral treatment with 82-2050 mg/kg NPM caused significant elevations in the serum urea and creatinine and full blood count parameters (except differential WBC counts). The elevated renal function parameters were corroborated by dose-related histological changes of renal tubular congestions. also caused profound thrombocytosis and histopathological changes of pulmonary interstitial widening and gastritis. In conclusion, NPM may not be considered safe for consumption on prolonged use and at a high dose due to its profound tendencies to cause pulmonary fibrosis, nephrotoxicity, gastritis and thrombo-embolism. However, all the biochemical and hematological but histopathological alterations induced by NPM were reversed 14 days after the treatment cessation.

Acridocarpus Smeathmannii (DC.) Guill. & Perr. Root enhanced reproductive behavior and sexual function in male wistar rats: Biochemical and pharmacological mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Novel therapeutic opportunities from medicinal agents continue to arouse scientific interest in recent times. Still, there is a dearth of information as regards experimental evidence generated from medicinal plants that would yield pharmacological agents for the treatment of erectile dysfunction. Acridocarpus Smeathmannii (DC.) Guill. & Perr. Root (ASR) has a long history as an aphrodisiac in African traditional medicine. Thus, this study investigated the reproductive potentials and associated biochemical mechanisms of its hydroethanolic extract (HEASR) in male Wistar rats. Also, the bioactive compounds were identified. MATERIALS AND METHODS: Fifty-four male albino rats (180 ±â€¯20 g) were divided into nine groups of six rats/group. Control, group 1 received normal saline (10 mL/kg). Groups 2-6 rats were administered sildenafil (1.43 mg/kg/day), mesterolone (0.36 mg/kg/day), doxazocin (0.03 mg/kg/day), HEASR1 (50 mg/kg/day) and HEASR2 (200 mg/kg/day) respectively. Others received co-administration of HEASR2 with standard drugs. Treatment lasted for 28 days via oral gavage. RESULTS: An acute oral toxicity of HEASR up to 2 g/kg produced no mortality in mice p.o. while the median lethal dose was estimated to be 810 mg/kg i.p. HEASR2 administration or in combination with sildenafil, mesterolone and doxazocin increased mounting frequencies on day 28 by 77.44%, 122.65%, 148.5% and 93.88% and sperm counts by 38.29%, 55.21%, 42.48%, and 48.98% respectively in treated rats. HEASR2 + sildenafil elevated testosterone and follicle stimulating hormone levels by 36.33% and 24.55% while HEASR2 + doxazocin elevated luteinizing hormone levels by 97.44% in rats. HEASR modulated prostate-specific antigen and malondialdehyde levels respectively. Reduced glutathione, superoxide dismutase, and catalase activities were raised in five selected organs. Serum nitric oxide but not cyclooxygenase-2 or tumor necrosis factor-α levels was moderately improved in rats. CONCLUSION: Overall, the results obtained demonstrated the potential of HEASR as a male reproductive enhancer, thus justify its folklore applications. Further, octadecanoic acid ethyl ester was the most abundant bioactive component present.

Toxicological evaluation of therapeutic and supra-therapeutic doses of Cellgevity® on reproductive function and biochemical indices in Wistar rats.

BACKGROUND: The misconception about dietary supplements being safe has led many into the in-patient wards. Cellgevity® (CGV) is a Max International premiere antioxidant supplement formula used by a large population. This study evaluated the effects of therapeutic and supra-therapeutic doses of CGV on reproductive function and biochemical indices in Wistar rats. METHODS: Seventy-two Wistar rats weighing 130 ± 15.8 g were grouped into two categories (male or female) of six rats per group. Control group received distilled water (10 ml/kg). Others received therapeutic (14.3 mg/kg or 28.6 mg/kg) and supra-therapeutic CGV doses (1000, 2000 or 3000 mg/kg) body weight per oral respectively. RESULTS: After 60 days, supra-therapeutic doses of CGV reduced sperm motility (p < 0.05) by 31.8%, 31.3% and 34.5% respectively and increased (p < 0.05) abnormality in sperms by 200%, 241% and 141.3% respectively. CGV altered male (luteinizing, follicle stimulating hormones and testosterone) and female reproductive hormones (luteinizing, follicle stimulating hormones estrogen and progesterone) respectively. Therapeutic doses of CGV elevated reduced glutathione, superoxide dismutase, catalase and glutathione S-transferase, although, this was exceeded by supra-therapeutic doses and more in females than male rats. Supra-therapeutic dose (3000 mg/kg CGV) decreased body weight in both male and female rats by 50% (F(1.5, 30) = 1.2, p = 0.041) and 62.7% (F(2.1, 30) = 0.38, p = 0.038) respectively in treated rats. Supratherapeutic (3000 mg/kg) dose of CGV increased (p < 0.05) creatinine level by 99.1% while serum total protein was reduced (p < 0.05) by 60.1% (2000 mg/kg) and 57.2% (3000 mg/kg) respectively in male animals. In Female rats, supra-therapeutic doses of CGV elevated creatinine levels by 72.2% (1000 mg/kg), 60.2% (2000 mg/kg) and 124.8% (3000 mg/kg) respectively and 3000 mg/kg produces elevated serum low density lipoprotein by 34.6% in treated rats. Serum cholesterol, triglycerides, albumin, alkaline phosphatase were unaltered by CGV dosing. Histology shows seminiferous tubules with reduced spermatogenic cells. Also, female rat kidney revealed acute tubular necrosis at highest dose used in this study. CONCLUSION: Overall, these data suggest that pro-oxidant potential of the supra-therapeutic CGV doses is evident. Hence, it is necessary that its administration be done with caution using appropriate doses.

Investigations into the Risk of Reproductive Toxicity Following Exposure to Highly Active Anti-Retroviral Drugs in Rodents.

With the introduction of Highly Active Antiretroviral Therapy (HAART), there has been drastic decline in morbidity and mortality associated with HIV/AIDS. However, many patients experience adverse drug reactions perhaps due to the inherent toxic nature of HAART. The possible toxic effect of HAART (combination ARVs) on reproduction and sexual dysfunction in seropositive HIV patients remains a subject of intense research. This study was designed to investigate the toxic effects of HAART on the reproductive hormones and organs of male and female rats. Sexually mature adult male and female rats were administered therapeutic doses of single and combination antiretroviral drugs for 48 days and thereafter sacrificed under anaesthesia. Morphological and histopathological examination of the testes and ovaries were carried out. Serum biochemical assay, semen quality analysis and hormonal assays were also conducted using standard methods. Results show significant (p < 0.05) reductions in the weight of testes and epididymis across all groups versus control; sperm count and motility were also significantly reduced in the test groups while hormonal analysis in males revealed significant reductions in LH, FSH and Testosterone. In the females, there was a significant (p < 0.05) reduction in the number of ovarian follicles, prolactin, estrogen and progesterone. We thus conclude that the administration of single and combined antiretroviral drugs have potential reproductive toxic effects.

Safety evaluation of Bon-santé cleanser® polyherbal in male Wistar rats: Further investigations on androgenic and toxicological profile.

BACKGROUND: The global increase in acceptance and use of herbal remedies in recent times is still accompanied with poor knowledge of their potential adverse effects and the toxicological implications of their use are underestimated. METHODS: Bon-santé Cleanser® (BSC), a polyherbal containing Anogeissus leiocarpus, Terminalia ivorensis, Massularia acuminate and Macuna pruriens, is an "energizer and hormone booster". We assessed the effect of BSC on reproductive function after administration for 60 days in male Wistar rats. Rats (150-300 g) were assigned into four groups of 8/group. Control received distilled water (10 ml/kg) while other groups received BSC 250, 500 and 1000 mg/kg/day p.o. respectively. Animals were euthanized by cervical dislocation and samples collected for analysis. RESULTS: BSC (250 mg/kg) elevated (p < 0.05) follicle stimulating hormone and luteinizing hormone levels respectively. BSC decreased sperm motility and the live-dead ratio at 1000 mg/kg and reduced reproductive hormone at 500 mg/kg and 1000 mg/kg respectively. BSC at 500 mg/kg increased (p < 0.05, F = 3.18-13.21) testicular reduced glutathione level (50.3%) and catalase (43.7%) but not activities of superoxide dismutase, glutathione S-transferase, and malondialdehyde level. Further, BSC influenced Mg, Zn, Cu, P, Mn, Ni and Fe levels (p < 0.05). BSC (1000 mg/kg) decreased testis weight (p < 0.05) and induced mild inflammation characterized by atrophic tubules. CONCLUSION: Overall, our data suggest BSC at low doses may increase reproductive hormones regulated by FSH and LH as observed in this study. However, BSC administration should be done with caution as it may induce reproductive toxicity in large doses.

Safety evaluation of Bon-santé cleanser® polyherbal in male Wistar rats.

BACKGROUND: The potential harm of medicinal herbs has been recently observed following herbal toxicity studies after ingestion of polyherbal remedies. This was the rationale for the food and drug regulatory agency decision for thorough safety evaluation of herbal medicines. Androgenic, antipyretic, analgesic and anti-inflammatory potentials as well as chemical compositions of extracts of massularia acuminata, terminalia ivorensis, anogeissus leiocarpus and macuna pruriens respectively have been documented. Thus, Bon-santé cleanser® (BSC) is formulated from these medicinal plants with the intention to boost body hormones and energizes the body. Considering the wide usage of BSC, we investigated on its safety in male Wistar rats. METHODS: Thirty-two male Wistar rats weighing 201.9 ± 7.5 g were grouped into four treatment groups of eight per group. Group I, (control) received distilled water (10 ml/kg). Groups II-IV received 250 mg/kg, 500 mg/kg and 1000 mg/kg of BSC per oral respectively. Each group was treated for sixty days. RESULTS: Acute toxicity test, in male Wistar albino mice, showed that LD50 was 600 mg/kg via i.p. while 4 g/kg was nonlethal after oral administration in mice. Hepatic and renal biomarker enzymes were unaltered in all rats. Increased in PCV (p <0.05) was observed at 500 mg/kg. BSC modulates antioxidants biomarkers following sub-chronic administration and increased serum Na(+) (p >0.05). BSC at 1000 mg/kg caused mild inflammation of the liver and heart but not kidneys histologically. CONCLUSIONS: BSC has been found to be relatively safe in Wistar rats. Although, our findings indicate that herbal therapy with BSC should be done with caution as a mild alteration in the liver and heart architectures were observed.

The combined fixed-dose antituberculous drugs alter some reproductive functions with oxidative stress involvement in wistar rats.

The reproductive toxicity of combined fixed-dose first-line antituberculosis (CFDAT) regimen was assessed in rats. Thirty-two (32) Wistar rats weighing 168.1 ± 8.0 g were divided into four groups of eight rats per group. Two groups of male and female rats were administered oral distilled water (1.6 ml) and CFDAT drugs containing rifampicin, isoniazid, pyrazinamide and ethambutol (RIPE, 92.5 mg/m2 per body surface area) respectively for forty-five days. Serum follicle stimulating hormone, luteinizing and testosterone were reduced significantly (p < 0.05) in the treated male rats. Similarly, sperm count levels were decreased by 27.3% when compared with control. RIPE elevated serum oestrogen (p < 0.05), progesterone (p < 0.05) as well as prolactin (p > 0.05) levels in the treated females. In addition, RIPE reduced (p < 0.05) total proteins levels and increased (p < 0.05, 53%) catalase levels in male but not female animals. Superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, reduced glutathione levels as well as lipid peroxidation were unaltered in all rats respectively. Histopathological studies revealed congested peritesticular vessels and no changes in the ovary when compared with control. Overall, our results demonstrate reproductive toxicity potentials of RIPE in the rat, thus, suggesting that these reproductive parameters be monitored during antituberculous chemotherapy.

Interplay between antiretroviral therapy and oxidative stress in HIV seropositive patients.

BACKGROUND: HIV infection results in a decline of CD4+ T-cells count and ultimately results in qualitative impairments of CD4+ T-cell function. Antiretroviral therapy results in an increase in the number of CD4+ cells and the functional reconstitution of the immune system. However, patients on therapy commonly experience adverse effects; management of HIV infection thus becomes a balancing act between the benefits of HIV suppression and the risks of drug toxicity with Highly Active Antiretroviral Therapy (HAART). Purpose and Findings: This review intended to look into the relationship between adverse effects with HAART in relation to its induction of oxidative stress in the host. From literature,. HAART has been shown to induce oxidative stress by several biochemical mechanisms. However, the induction of oxidative stress by HAART is minimal compared to HIV induction of oxidative stress-in the host. The use of HAART in the management of HIV-AIDS thus remains inevitable and the combination with exogenous antioxidants is advocated. Exogenous antioxidants mop up infection induced reactive oxygen species (ROS), and may also be beneficial in ameliorating some of the adverse effects induced by HAART. CONCLUSION: Further review on individual adverse effects of ART is recommended and our ongoing research on the teratogenic potentials of HAART will also be very relevant on this subject.

A prospective study of adverse events to antiretroviral therapy in HIV- infected adults in Ekiti State, Nigeria.

OBJECTIVES: Highly active antiretroviral therapy (HAART); the-current standard of antiretroviral therapy for Human Immunodeficiency Virus (HIV) infected persons, has been documented to drastically, reduce the number of cases of Acquired Immune Deficiency Sypdrome (AIDS). However, adverse. events are a challenge to the use of HAART. This study intends to determine the nature and incidence of suspected advcrse events to prescribed anti retroviral drugs in treatment centers in Ekiti State. METHOD: One hundred and twenty participants were enrolled and followed up over a period of six months. At each clinic visit, there was an administration of a detailed interviewer questionnaire that was completed by the attending pharmacist together with the participant. The form is designed to obtain information on the demographics of the patients, WHO clinical stage of their HIV infection, HAART regimen for the patients, and suspected adverse events associated with the antiretroviral drugs used by the patients. RESULTS: Tenofovir/Lamivudine/Eifavirenz (72.5%), Zidovudinc/Lamiv.udin/Nevirapine (16.7%), Zidovudine/Lamivudiine/ElafIvirenz (6.7%), Tenofovir/ Lamivudine/Nevirapine (3.3%), and Abacavir/ Lamivudine/Nevirapine (0.8%) were the HAART regimens prescribed to the patients. About half (57%) of the participants reported clinical adverse events; 92% of which were reported within two weeks of HAART initiation. Most of the reported adveise events were nausea (14.5%), abdominal discomfort (8.2%), and insomnia (7.5%). A few (6%) of those who reported adverse events required regimen switch or drug substitution. CONCLUSIONS: Antiretroviral drugs exposure often presents with adverse events, an observation similar to other studies. Most of the clinical adverse events were not severe or life threatening.

Evaluation and Comparison of the Indices of Systemic Oxidative Stress among Black-Africans with Age-related Cataracts or Primary Glaucoma.

PURPOSE: Oxidative stress has been implicated in the pathophysiology of glaucoma, cataract, and many degenerative diseases. The purpose of this study is to evaluate the systemic oxidative stress in black-African patients diagnosed with primary glaucoma or age-related cataract (ARC) and compare these indices to normal control patients and between the two conditions. METHODS: This was a descriptive cross-sectional study of consecutive recruited subjects attending a tertiary care facility. One hundred adults were enrolled and sub-grouped into: Normal controls (n = 20), patients with primary glaucoma (n = 40), and patients with cataract (n = 40). The data were collected on patient demographics and clinical information. Ten milliliters of the venous blood was taken from each subject for the evaluation of serum biochemical indices of oxidative stress. Laboratory measurements of enzymatic and nonenzymic anti-oxidants, as well as lipid peroxidation, were conducted using established and validated spectrophotometric methods. The systemic oxidative stress was measured by the serum levels of anti-oxidant enzymes and lipid peroxidation, and compared between the groups and to a control group of patients. RESULTS: Statistically, significantly reduced serum levels of glutathione, glutathione-S-transferase, superoxide dismutase, catalase, and ascorbic acid were found in the patients with glaucoma or cataract when compared with controls (P < 0.05 for all). Differences in serum lipid peroxidation levels across or between the groups were nonsignificant. Serum protein levels were significantly higher among the subjects with cataract or glaucoma than in controls. CONCLUSION: Our results concur with findings in Caucasian study cohorts. This indicates that in black-Africans, primary glaucoma, and ARC are associated with increased systemic oxidative stress. This supports the existing evidence on the role of oxidative stress in these ocular disorders and reinforces the rationale for the use of anti-oxidants in the management and possible prevention of these conditions.

Prescribing Pattern of Non-Steroidal Anti-Inflammatory Drugs at the Outpatient Pharmacy Department of a University Teaching Hospital in Nigeria.

BACKGROUND: Non-steroidal Anti-inflammatory Drugs (NSAID), are among the most widely used and misused of all drugs. Though they provide symptomatic relief from pain and swelling in chronic joint diseases, they may cause renal impairment, especially in combination with other nephrotoxic agents. OBJECTIVES: This study aimed to investigate the prescription pattern of NSAID in the Out-patient Pharmacy Department of Lagos University Teaching Hospital (LUTH), Nigeria. DESIGN: A total of 3800 prescriptions containing NSAIDs were analyzed for information on drug name, the number of NSAIDs per prescription, the presence of ACE inhibitors and diuretics alongside NSAIDs and NSAIDs prescribed in generic or brand names. RESULTS: The results showed that Aspirin was the most frequently prescribed NSAID (62.2%) and 68.4% of the NSAIDs prescriptions studied were written in generic names. The total number of drugs per prescription was in most cases 3 or greater (84.6%). There were statistically significant (p ≤ 0.05) associations between the individual NSAID prescribed and whether they were prescribed in generics or brand names; individual NSAID prescribed and the frequency of co-prescription with an ACE inhibitor and a diuretic; types of NSAID prescribed and the cost in Naira. CONCLUSION: Though most of the prescribers complied with WHO standard in their prescriptions vis a vis generic prescription, avoidance of polypharmacy and avoidance of drug interactions and contraindications, there is obvious need for interventional measures or strategies to improve rational prescribing for some of the prescribers tailored towards rational prescription and use of drugs.

Polycyclic Aromatic Hydrocarbon, Haematological and Oxidative Stress Levels in Commercial Photocopier Operators In Lagos, Nigeria.

BACKGROUND: Human exposure to hazardous substances in the environment has been known to play an important role in the pathogenesis of some diseases. Photocopying machines have become a cheap source of self-employment in Nigeria. For obvious reasons the highest level of patronage is encountered in the campuses of educational institutions. However, the persons who operate the machines are always exposed to possible hazards associated with the job without protective devices. OBJECTIVE: This study investigated the levels of oxidative stress, polycyclic aromatic hydrocarbon (PAH) and haematological parameters in blood samples of photocopier operators. METHODS: The experimental procedure involved 50 consented subjects selected based on some criteria. The haematological parameters, oxidative stress and PAH levels were determined using standard methods. RESULTS: The results showed no significant difference (p ≥ 0.05) in the haematological parameters between the test subjects and the controls. However, there were duration on the job (yrs) dependent significant decrease in the level of superoxide dismutase (SOD) of the photocopier operators compared with the controls (> 5 years p≤ 0.0001; 4-5 years p≤0.001). The level of reduced glutathione (GSH) was significantly decreased across all lengths of duration on the job compared with the controls. CONCLUSION: The findings in this study revealed increased level of oxidative stress in photocopier operators with no significant change in haematological parameters. The health implication of operating photocopiers call for quick health education and intervention tailored to monitoring and guiding the photocopier operators. This will help to prevent or manage continuous exposure to the hazards of photocopying machines.

Adverse drug reactions amongst adult patients admitted in Lagos State University Teaching Hospital Lagos, Nigeria.

BACKGROUND: Adverse drug reaction (ADR) is a global drug therapy problem. It has been rated as one of the top leading causes of morbidity and mortality. In Nigeria, not much is known about ADRs especially with the existing weak post marketing surveillance for monitoring drug use, and its effect on the population. OBJECTIVES: The study is aimed at determining the incidence of ADRs, presentations of ADRs, classes of drugs that frequently cause ADRs and predictors of ADRs in adult medical in-patients in LASUTH. METHOD: A retrospective study of six hundred and twenty four (624) case notes of all patients admitted to the medical wards in LASUTH between January 1, 2009 and December 31, 2009 was carried out. Information obtained included age, gender, and adverse drug reaction and drug details. The results obtained were analyzed using SPSS version 16 statistical software. Level of significance was set at p ≤ 0.05. RESULTS: A total of 624 case notes consisting of 358 males and 266 females were assessed. The number of patients who experienced adverse drug reactions was 67 (n = 624, 10.7%). The incidence rate of ADRs in LASUTH from the study was 10.7 per 100 patients' population. Most of the ADRs observed were type A reactions (97.8%). Mostly implicated classes of drugs were antidiabetics (26.7%) and NSAIDs (29.3%). CONCLUSION: The incidence rate of ADRs was 10.7%. ADRs which are predictable and preventable occur in hospitalized patients, such may be prevented or minimized by implementing measures to target specific drugs that are commonly suspected.

Prescribing Pattern of Non-Steroidal Anti-inflammatory Drugs at the Outpatient Pharmacy Department of Lagos University Teaching Hospital; Nigeria

Background: Non-steroidal Anti- inflammatory Drugs (NSAID); are among the most widely used and misused of all drugs. Though they provide symptomatic relief from pain and swelling in chronic joint diseases; they may cause renal impairment; especially in combination with other nephrotoxic agents.Objectives: This study aimed to investigate the prescription pattern of NSAID in the Out-patient Pharmacy Department of Lagos University Teaching Hospital (LUTH); Nigeria.Design: A total of 3800 prescriptions containing NSAIDs were analyzed for information on drug name; the number of NSAIDs per prescription; the presence of ACE inhibitors and diuretics alongside NSAIDs and NSAIDs prescribed in generic or brand names. Results: The results showed that Aspirin was the most frequently prescribed NSAID (62.2) and 68.4 of the NSAIDs prescriptions studied were written in generic names. The total number of drugs per prescription was in most cases 3 or greater (84.6). There were statistically significant (p ? 0.05) associations between the individual NSAID prescribed and whether they were prescribed in generics or brand names; individual NSAID prescribed and the frequency of co-prescription with an ACE inhibitor and a diuretic; types of NSAID prescribed and the cost in Naira. Conclusion: Though most of the prescribers complied with WHO standard in their prescriptions vis a vis generic prescription; avoidance of polypharmacy and avoidance of drug interactions and contraindications; there is obvious need for interventional measures or strategies to improve rational prescribing for some of the prescribers tailored towards rational prescription and use of drugs

A study on pharmacovigilance of herbal medicines in Lagos West Senatorial District, Nigeria.

BACKGROUND: There is an increasing use of herbal products and herbal medicines globally with the belief that herbal medicines are always 'safe' and carry no risk because they are from natural sources. However, there are concerns regarding medicinal plants and their ability to produce adverse effects. The growing herbal medicine usage has increased the need to monitor the safety of herbal medicines. Thus, the recommended approach by the World Health Organization (WHO) is to include herbal medicines in existing national pharmacovigilance systems. OBJECTIVE: This study aimed to determine the knowledge of pharmacovigilance of herbal medicines amongst herbal medicine practitioners. METHODS: The study was carried out in Lagos West Senatorial District of Lagos State, Nigeria. Three categories of practitioners (378 respondents) were engaged and they include Traditional Herbal Sellers, Natural Health Practitioners and Pharmacists. RESULTS: The results showed that herbal medicines are commonly recommended for malaria, typhoid, diabetes and fever. 281 (74.3%) of the respondents claimed that herbal medicines have no adverse effects and only 91 (24.1%) of the respondents said there were some adverse effects reported by the users. Adverse effects reported include nausea, diarrhoea and weight loss. Amongst those that received reports of adverse effects, only 19 (20.9%) documented these reported adverse effects; none of these documentations were forwarded to the regulatory bodies or national pharmacovigilance centre in Nigeria. CONCLUSIONS: These results showed inadequate adverse effects monitoring (Pharmacovigilance) amongst the practitioners and underscore the necessity to educate and enlighten herbal medicine practitioners on the need for pharmacovigilance activity of herbal products.

Traditional medicinal plants in Nigeria--remedies or risks.

ETHNO-PHARMACOLOGICAL RELEVANCE: Soil pollution due to increasing industrialization is a reality that is taking its toll on mankind today. Considering the population of people that use herbal remedies especially in developing countries and the discharge of industrial waste on surrounding herbal vegetation, it is imperative to determine the heavy metals contamination in some commonly used medicinal plants. MATERIALS AND METHODS: Representative samples of five medicinal plants Ageratum conyzoides, Aspilia africana, Alchornea cordifolia, Amaranthus brasiliensis and Chromolaena odorata were collected from Ikpoba-Okha L.G.A, Edo State Nigeria, around a paint company and another set of same plants were collected from a non-polluted source. Dried leaves and roots of collected plants were digested and analyzed using Atomic Absorption Spectrophotometer (AAS) for the presence of Lead (Pb), Cadmium (Cd), Chromium (Cr), Nickel (Ni) and Zinc (Zn). Soil samples from polluted and non-polluted areas were also analyzed to ascertain the levels of these heavy metals in the environment. RESULTS: Results show that the concentrations of these heavy metals in the leaves and roots of plants collected from polluted soil were significantly higher than those obtained from unpolluted soil. Correspondingly heavy metal concentrations were significantly higher in polluted than in unpolluted soil samples. CONCLUSION: As part of continuing effort in the standardization of traditional remedies, environmental contamination control and abatement is evident. The source of medicinal plants/herbs should also be a cause for concern since the toxicity of medicinal plants is sometimes associated with environmental sources of the plants.

Haematotoxic and reproductive toxicity of fixed dose combined anti-tuberculous agents: protective role of antioxidants in rats.

BACKGROUND: Tuberculosis (TB) is the world's greatest infectious killer of women of reproductive age and the leading cause of death among people with HIV/AIDS. The major problem militating against the management of tuberculosis is the lack of compliance to medication by the infected patients as a result of multidrug needed to be taking daily leading to resistance. Occurrences of hepatic toxicity, teratogenicity, sperm quality damage, haematotoxicity and meningeal congestion of individual anti-tuberculous agents have been reported. OBJECTIVE: The study is aimed to determine the reproductive and haematological toxicity of combined antituberculous agents and the modulatory role of antioxidants using animal model. METHODS: Fifty rats (10 per group) were randomly allotted to five groups, consisting of the control, the fixed dose combined anti TB agents treated group, the fixed dose combined anti TB agents plus vitamin C treated group, the fixed dose combined anti TB agents plus vitamin E treated group and the fixed dose combined anti TB agents plus vitamin C plus vitamin E treated group. Therapeutic doses of the fixed dose combined anti TB agents (25 mg/kg/day), vitamin E (5 mg/kg) and vitamin C (8 mg/kg) were administered to the animals via oral gavage, daily over 28 days. After 28days, rats were sacrificed for internal macroscopic and histological examination of the organs, sperm analysis and haematological investigations were carried out. RESULTS: The results showed a significant increase (p < or = 0.05) in the levels of white blood cells (WBC), red blood cell (RBC) and haemoglobin (HB) of the combined anti-TB plus vitamins C or E treated groups compared with combined anti-TB treated group alone (56.34 +/- 0.11) that decreased the haematological parameters. A significant decrease (p < or = 0.05) in the sperm counts (22.26 +/- 0.02; 35.40 +/- 0.02) and motility (77.03 +/- 0.02; 94.50 +/- 0.01) of the combined anti-TB treated rats as compared with the control group were observed. The combined anti-TB plus vitamin C treated rats demonstrated a significant increase (p < or = 0.05) in the sperm motility (90.23 +/- 0.01) as compared with the control group. There was also a remarkable decrease in the abnormal morphology of the sperm in the combined anti-TB plus vitamins E and C treated rats (0.05 +/- 0.02) as compared with the combined anti-TB group alone (1.10 +/- 0.02). CONCLUSION: Vitamins C and E positively modulated the sperm quality and haematological damage produced by the Fixed Dose Combined Anti-Tuberculous agents.

Assessing the risk of birth defects associated with exposure to fixed-dose combined antituberculous agents during pregnancy in rats.

Due to the risks of disease progression and transmission to the newborn, treatment of tuberculosis is often pursued during pregnancy and fixed-dose combined antituberculous agents have been found to be beneficial. Unfortunately, there is paucity of data on the safety of the fixed-dose combined antituberculous drugs during pregnancy. This study intends to assess the teratogenic effect of fixed-dose combined antituberculous drugs on the organogenesis stage of fetal development and also investigate the possible roles of vitamin C in modulating the teratogenic effects of these agents on the fetus using animal model. Pregnant rats were divided into 3 groups with 12 animals per group: group 1 received distilled water (10 mL/kg) orally; group 2 received 51.4 mg/kg/day of fixed-dose combined antituberculous agents orally; group 3 received 51.4 mg/kg/day of fixed-dose combined antituberculous agents plus vitamin C (10 mg/kg/day) orally. Six rats in each group were randomly selected and sacrificed on day 20 by cervical dislocation prior to day 21 of gestation, and the foetuses were harvested through abdominal incision for physical examination. Blood samples were collected from the 1st filial rats of the remaining six animals for biochemical and hematological examination. The liver, kidney, heart, and brain of all the sacrificed animals were used for histopathological examination. There were significant (P ≤ 0.05) low birth weights of the foetuses of the animals that were treated with fixed-dose combined antituberculous agents. The haematological parameters also revealed a reduction in the platelets counts and neutrophiles at the first filial generation. Significant (P ≤ 0.05) elevations in the levels of aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the foetuses of the animals treated with fixed-dose combined antituberculous agents were also observed. However, the combination of vitamin C with fixed-dose combined antituberculous agents significantly (P ≤ 0.05) reduced the level of AST. Fixed-dose combined antituberculous agents have teratogenic potential as shown in low birth weight and mild liver damage in the first filial of the treated animals. As much as it is imminent to treat TB patients in pregnancy, there is need to always exercise caution and clinically weigh the risk-benefit ratio.

Assessment of genetic diversity of 12 populations of Azadirachta indica A. Juss from three different locations in Lagos State, Nigeria using RAPD markers.

BACKGROUND: The beneficial effects of plant materials typically result from the combination of secondary products present in the plant. Neem tree is a common source of natural products for development of medicines against various diseases. OBJECTIVE: This study was aimed at determining the genetic relatedness of neem (Azadirachta indica A. Juss) collected from three locations in Lagos State. METHODS: Leave samples were collected and DNA was extracted using Dellarporta method with modifications. Several random amplified polymorphic DNA (RAPD) primers were screened for polymorphism and amplifications and only six that showed good amplifications and polymorphism were selected for DNA amplification. RESULTS: The polymerase chain reaction (PCR) produced a total of 51 bands from 6 primers. Primer AC07 gave the highest numbers of polymorphic bands (12) while AG1 produced the least with 5 polymorphic bands when the products were run on agarose gel. An unweighted pair group method with arithmetic mean (UPGMA) dendrogram generated, grouped the samples into one single cluster with two major subgroups. The 12 populations showed no variation in their genomic composition based on their location. CONCLUSION: This is an indication of homogeneity in the population of neem plants collected from different locations with a possible consistency in pharmacological activities if investigated.