Search

Background Nevirapine is used in many developing countries for the management of HIV-1 patients. Despite its usefulness, hypersensitivity reaction is a common complication that accounts for patients defaulting during therapy in Ghana. Genetic variations in drug-metabolizing enzymes have been implicated in reported adverse drug reactions observed in patients on nevirapine regimen. The study determined genotypic frequencies of specific CYP2B6 and SULT1A1 variants and their association with nevirapine hypersensitivity among persons living with HIV in the Ghanaian population.Methods An unmatched case-control study was conducted in a tertiary health facility in Ghana. Baseline clinical data were recorded from the patients’ folder. Genomic DNA (gDNA) samples were genotyped for CYP2B6*18 (c.983T > C) and SULT1A1*2 (c.638G > A) using Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP).Results Mean age of the patients was 38 ± 9.47 years with the majority 77.1% (54/70) of the participants being females. For CYP2B6*18 (c.983T > C) genotype frequencies, T/T and T/C were 94.3% (66/70) and 5.7% (4/70) respectively while for SULT1A1*2 (c.638G > A) genotype frequencies, G/G, G/A, and A/A were 61.4% (43/70), 34.3% (24/70) and 4.3% (3/70) respectively. The prevalence of CYP2B6*18 (c.983T > C) and SULT1A1*2 (c.638G > A) minor allele were 2.9% (4/140) and 21.4% (30/140) respectively among the study participants.Conclusion Extensive metabolizer genotypes for CYP2B6*18 (c.983T > C) and SULT1A1*2 (c.638G > A) were more common than the intermediate and poor metabolizer genotype. However, CYP2B6 983C/C representing poor metabolizers of CYP2B6*18 (c.983T > C) were not detected among the study population. Genetic polymorphism of CYP2B6*18 (c.983T > C) and SULT1A1*2 (c.638G > A) were not associated with nevirapine hypersensitivity. However, these variants may contribute to differential variations of other drug responses among the Ghanaian population.

Introduction: Major depressive disorder is often associated with suicidal tendencies, and this condition accentuates the need for rapid-acting antidepressants. We previously reported that Alkaloids (ALK) from Trichilia monadelpha possess antidepressant action in acute animal models of depression and that this effect is mediated through the monoamine and L-arginine-NO-cGMP pathways. This study investigated the possible rapid-onset antidepressant effect of ALK from T. monadelpha and its connection with the glycine/NMDA receptor pathway. Methods: The onset of ALK action from T. monadelpha was evaluated using the Open Space Swim Test (OSST), a chronic model of depression. The modified forced swimming and tail suspension tests were used to assess the effect of the ALK on the glycine/NMDA receptor pathway. The Instutute of Cancer Research (ICR) mice were treated with either ALK (30–300 mg/kg, orally [PO]), imipramine (3–30 mg/kg, PO), fluoxetine (3–30 mg/kg, PO), or saline. To identify the role of glycine/NMDA receptor pathway in the effect of ALK, we pretreated mice with a partial agonist of the glycine/NMDA receptor, D-cycloserine (2.5 mg/kg, intraperitoneally [IP]), and an agonist of glycine/NMDA receptor, D-serine (600 mg/kg, IP), before ALK administration. Results: ALK reversed immobility in mice after the second day of drug treatment in the OSST. In contrast, there was a delay in the effects induced by fluoxetine and imipramine. ALK also increased mean swimming and climbing scores in mice. ALK was more efficacious than imipramine and fluoxetine in reducing immobility and increasing distance traveled. It is noteworthy that ALK was less potent than fluoxetine and imipramine. D-cycloserine potentiated mobility observed in the ALK- and fluoxetine-treated mice. In contrast, D-serine decreased mobility in the ALK-treated mice. Conclusion: The study results suggest that ALK from T. monadelpha exhibits rapid antidepressant action in mice, and the glycine/NMDA receptor pathway possibly mediates the observed effect.

Unsweetened natural cocoa (UNCP) was evaluated for reproductive toxicity in rats. A preliminary genotoxic potential was evaluated by the DNA comet assay test using C57Bl/6 mice. Both therapeutic dose (TD; 900 mg/kg) and high dose (HD; 9000 mg/kg) of UNCP were used. White Wistar rats were used in two experimental groups. The females received UNCP 15 days before crossing with untreated males. The males received UNCP for 48 days before mating with untreated females. Subacute toxicity was observed during a 14-day oral administration of UNCP. Results show that a high tail DNA% was observed with methyl mesylate administration in all tissues analysed. The lowest tail DNA% value was observed in the liver (1.64 ± 0.26) and kidney (1.63 ± 0.30) during UNCP (TD) administration. UNCP did not induce observable physical congenital malformations on the pubs of treated female and male rats, lacks genotoxic potential, and did not adversely affect pregnancy index, pub weights, and survival index, but UNCP exhibited proimplantation potential ( p > 0.05 ).

Background Nymphaea lotus L. (N. lotus) is an aquatic plant with anecdotal reports suggesting its use in the traditional management of cancer. However, there is a paucity of data on the antioxidant, anti-inflammatory and cytotoxic properties of N. lotus in relation to its phytochemical and elemental contents. This study aimed at determining the antioxidant, anti-inflammatory and cytotoxic properties of the hydro-ethanolic extract of N. lotus leaves (NLE), and its phenolic, flavonoid and elemental constituents. Methods The antioxidant property of NLE was determined using total phenolic and flavonoid, DPPH radical scavenging, lipid peroxidation and reducing power assays. The anti-inflammatory activity of NLE (100–250-500 mg/kg), diclofenac and hydrocortisone (positive controls) were determined by paw oedema and skin prick tests in Sprague Dawley rats. Also, the erythrocyte sedimentation rate (ESR) was determined by Westergren method. The macro/micro-elements content was determined by the XRF method. The cytotoxic property of NLE was determined by the MTT assay, on two cancer cell lines (MCF-7 and Jurkat) and compared to a normal cell line (Chang liver). Inhibitory concentrations were determined as IC50 values (±SEM). Results The extract had appreciable levels of phenolic and flavonoids compounds and was two-fold more potent in scavenging DPPH radicals than Butylated hydroxytoluene (BHT). However, NLE was three- and six-fold less potent than ascorbic acid and BHT, respectively, in reducing Fe3+ to Fe2+. The extract was six-fold more potent than gallic acid in inhibiting lipid peroxidation. The extract caused a dose-dependent decrease in rat paw oedema sizes, comparable to diclofenac, and a significant decrease in wheel diameters and ESR. The elemental analysis revealed relevant concentrations of Mg2+, P2+, S2+, K2+, Mn+, Fe+, Cu+, Zn+ and Cd+. The extract exhibited cytotoxic activity on both MCF-7 (IC50 = 155.00 μg/ml) and Jurkat (IC50 = 87.29 μg/ml), with higher selectivity for Jurkat cell line. Interestingly, the extract showed low cytotoxicity to the normal Chang liver cell line (IC50 = 204.20 μg/ml). Conclusion N. lotus leaves extract exhibited high antioxidant, anti-inflammatory and cancer-cell-specific cytotoxic properties. These aforementioned activities could be attributed to its phenolic, flavonoid and elemental constituents. Graphical abstract

Ethnopharmacological relevance Some local communities in Cote d'Ivoire use the mushroom Termitomyces schimperi combined with kaolin (TSK) to manage various cancers in patients. However, there is a paucity of data on toxicity, mutagenicity and trace metal constituent of TSK. Aim of the study We sought to investigate the acute and sub-chronic toxicities, mutagenic potential, and trace metal constituents of TSK. Materials and methods To assess acute toxicity, single doses (1000, 3000 and 5000 mg/kg) of aqueous extract of TSK were administrated per os to Sprague Dawley (SD) rats on Day 1. The rats were then monitored for 13 consecutive days. Sub-chronic toxicity was evaluated by daily administration of 200 and 500 mg/kg of the extract per os for 90 consecutive days. SD rats used as control received distilled water. Signs of toxicity, changes in body weight and mortality were monitored. After the aforementioned monitoring processes, rats were sacrificed and blood collected for full blood count and biochemistry analysis. Animal organs were also collected for histopathological examination. The mutagenic potential of the aqueous extract of TSK (10000 μg/mL) on TA98 Salmonella typhimurium was estimated. Additionally, energy-dispersive X-ray fluorescence (ED-XRF) method was employed to determine trace metal constituents of TSK. Results Single-dose administration of 5000 mg/kg of TSK did not cause any death in the SD rats; thus, LD50 was above 5000 mg/kg. Administration of 1000 and 3000 mg/kg of the aqueous extract of TSK did not cause any significant change in behaviour and body weight of SD rats during the 14-day monitoring period. However, the mean corpuscular volume and the mean corpuscular haemoglobin concentration increased significantly (p = 0.0122) in serum creatine level among rats administered 1000 and 3000 mg/kg of TSK extract compared with control. After 14 days, there were minimal changes with isolated organs of TSK-treated and control rats. Furthermore, 90-day treatment with extract of TSK caused no significant change in parameters assessed. TSK induced frameshift gene mutation in S. typhimurium before (p Conclusions The aqueous extract of TSK showed no toxicity (acute and sub-chronic) at doses tested. These findings are consistent with the absence of heavy metals (i.e., cadmium) and potentially toxic elements (i.e., uranium) in TSK samples analysed. TSK showed some level of mutagenic potential. Further mutagenic and chronic toxicity studies on TSK are required.

Introduction: Major depressive disorder is often associated with suicidal tendencies, and this condition accentuates the need for rapid-acting antidepressants. We previously reported that Alkaloids (ALK) from Trichilia monadelpha possess antidepressant action in acute animal models of depression and that this effect is mediated through the monoamine and L-arginine-NO-cGMP pathways. This study investigated the possible rapid-onset antidepressant effect of ALK from T. monadelpha and its connection with the glycine/NMDA receptor pathway. Methods: The onset of ALK action from T. monadelpha was evaluated using the Open Space Swim Test (OSST), a chronic model of depression. The modified forced swimming and tail suspension tests were used to assess the effect of the ALK on the glycine/NMDA receptor pathway. The Instutute of Cancer Research (ICR) mice were treated with either ALK (30–300 mg/kg, orally [PO]), imipramine (3–30 mg/kg, PO), fluoxetine (3–30 mg/kg, PO), or saline. To identify the role of glycine/NMDA receptor pathway in the effect of ALK, we pretreated mice with a partial agonist of the glycine/NMDA receptor, D-cycloserine (2.5 mg/kg, intraperitoneally [IP]), and an agonist of glycine/NMDA receptor, D-serine (600 mg/kg, IP), before ALK administration. Results: ALK reversed immobility in mice after the second day of drug treatment in the OSST. In contrast, there was a delay in the effects induced by fluoxetine and imipramine. ALK also increased mean swimming and climbing scores in mice. ALK was more efficacious than imipramine and fluoxetine in reducing immobility and increasing distance traveled. It is noteworthy that ALK was less potent than fluoxetine and imipramine. D-cycloserine potentiated mobility observed in the ALK- and fluoxetine-treated mice. In contrast, D-serine decreased mobility in the ALK-treated mice. Conclusion: The study results suggest that ALK from T. monadelpha exhibits rapid antidepressant action in mice, and the glycine/NMDA receptor pathway possibly mediates the observed effect.

Background. There is considerable evidence that many patients concurrently administer dietary supplements with conventional drugs, creating a risk for potential drug-supplement interaction. The aim of this study was to determine the effect of Cellgevity® supplement on selected rat liver cytochrome P450 (CYP) enzymes. Also, based on our previous finding, we sought to determine the effect of Cellgevity® on the pharmacokinetics of carbamazepine, a CYP3A4 substrate. Methods. Male Sprague–Dawley (SD) rats were randomly put into 5 groups and administered either distilled water (negative control), Cellgevity® (3 separate doses), or phenobarbital (positive control), per os. Modulation of liver CYP enzyme activity was evaluated after 30 days of treatment, using probe substrates, spectroscopic, and high-performance liquid chromatographic methods. In the pharmacokinetic study, 12 SD rats were put into 2 groups and administered carbamazepine plus normal saline (group 1) or carbamazepine plus Cellgevity® (group 2), per os, both over a period of 14 days. Blood samples from rats in the same group were collected after treatment. Serum samples were prepared and pooled together at each specific sampling time point. Levels of carbamazepine were determined using a fluorescence polarization immunoassay. Results. Activities of rat liver CYP1A1/2, CYP2C9, and CYP2D6 were significantly increased by Cellgevity® after 30-day treatment. Pharmacokinetic parameters for rats administered carbamazepine with Cellgevity® vis-a-vis carbamazepine with normal saline were as follows: Cmax; 20 μmol/L vs 11 μmol/L, AUC0⟶24; 347 μmol h/L vs 170 μmol h/L, Ke; 0.28 h−1 vs 0.41 h−1, and t1/2; 2.3 h vs 1.7 h, respectively. Conclusions. Cellgevity® increased the activity of rat CYP1A1/2, CYP2C9, and CYP2D6 enzymes and was found to alter the pharmacokinetics of carbamazepine in rats.

ETHNOPHARMACOLOGICAL RELEVANCE Advancement in cancer therapy has improved survival among patients. However, use of anticancer drugs like anthracyclines (e.g., doxorubicin) is not without adverse effects. Notable among adverse effects of doxorubicin (DOX) is cardiotoxicity, which ranges from mild transient blood pressure changes to potentially serious heart failure. Anecdotal reports suggest that Kalanchoe integra (KI) may have cardio-protective potential. AIMS OF THE STUDY This study sought to determine the cardio-protective potential of KI against doxorubicin-induced cardiotoxicity and also examined any possible genotoxic potential of KI in selected organs. Additionally, the nitric oxide modulatory potential of KI was assessed. MATERIALS AND METHODS The leaves of KI were collected, air-dried, pulverised and extracted using 70% ethanol. High-performance liquid chromatography (HPLC) fingerprinting was done for KI. Also, the single-cell gel electrophoresis assay (Comet assay) was employed to ascertain the genotoxic potential of KI. In assessment of cardio-protective potential of KI against doxorubicin-induced cardiotoxicity, a total of 42 female Sprague-Dawley rats were put into 7 groups (n = 6). Group I: vehicle control, received normal saline (1 mL/kg p.o) for 30 days. Group II: toxic control, received DOX (20 mg/kg i.p.) once on the 29th day. Group III: KI control, received KI (300 mg/kg p.o) for 30 days. Group IV: vitamin E control, received vitamin E (100 mg/kg p.o) for 30 days. Group V: KI treated-1, received KI (300 mg/kg p.o) for 30 days and DOX (20 mg/kg i.p) on the 29th day. Group VI: KI treated-2, received KI (600 mg/kg p.o) for 30 days and DOX (20 mg/kg i.p) on the 29th day. Group VII: vitamin E treated, received vitamin E (100 mg/kg p.o) for 30 days and DOX (20 mg/kg i.p) on the 29th day. Thirty-six (36) hours after last administration, rats were sacrificed. Blood samples were taken via cardiac puncture to determine levels of aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), creatine kinase (CK), lactate dehydrogenase (LDH), enzymatic antioxidants such as glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). Nitric oxide level was also determined. Hearts of rats in each group were excised and taken through histopathological examination. RESULTS In the HPLC fingerprint analysis, 13 peaks were identified, and peak with retention time of 24.0 min had the highest peak area (3.223 x104 mAU). Comet assay showed that the KI extract was non-genotoxic. Pretreatment with KI protected rats against doxorubicin-induced cardiotoxicity as evidenced by the low levels of AST, ALT, ALP, CK and LDH compared with the controls (p

BackgroundThere is considerable evidence that many patients concurrently take dietary supplements with conventional drugs, with a risk of potential drug-supplement interaction. The aim of this study was to determine the effect of Cellgevity® supplement on selected rat liver cytochrome P450 (CYP) enzymes and on the pharmacokinetics of carbamazepine.MethodsSprague-Dawley (SD) rats were put into 5 groups and modulation of CYP enzyme activity by Cellgevity® was determined by comparing the enzyme activity of Cellgevity-treated groups with the negative control group after 30 days of treatment. For the effect of Cellgevity® on the pharmacokinetics of carbamazepine, 12 SD rats were put into 2 groups; one group received an oral administration of carbamazepine plus Cellgevity®, and the other carbamazepine plus normal saline. Blood samples were collected at specific time points and analyzed for levels of carbamazepine. ResultsActivities of CYP1A1/2, CYP2C9 and CYP2D6 were significantly increased by Cellgevity®. The pharmacokinetic parameters for rats administered carbamazepine with Cellgevity® vis-a-vis carbamazepine with normal saline were changed as follows: Cmax; 20 μmol/L vs 11 μmol/L, AUC0→24; 347 μmol.h/L vs 170 μmol.h/L, Ke; 0.28 h-1 vs 0.41 h-1, and t1/2; 2.3 h vs 1.7 h, respectively.ConclusionsCellgevity® increased the activity of rat CYP1A1/2, CYP2C9 and CYP2D6, and also altered the pharmacokinetics of carbamazepine in rats.

Background: Unsweetened natural cocoa powder (UNCP), prepared after removal of the cocoa butter, is a common beverage in Ghana. It possesses antimalarial prophylactic property and has a beneficial effect on blood components. Aim: The aim of this study was to determine whether regular dietary supplement of UNCP mitigates high-dose (HD) artemether-lumefantrine (A-L)-induced hematological disorders and to determine the effect on nitric oxide (NO) levels. Materials and Methods: Adult male guinea pigs (300 g - 350 g) were randomly divided into 5 groups of 6 guinea pigs each. Among the 5 groups, 3 groups were treated with UNCP (300, 900, and 1500 mg/kg body weight) for 14 days. A-L (75 mg/kg) was administered from the 12th to 14th day. One of the remaining 2 groups received distilled water only, i.e., vehicle control group (VCG) while the other received 75 mg/kg A-L only, i.e., negative control group (NCG). Blood samples from all groups were obtained by cardiac puncture (day 15) followed by hematological and NO analysis. Results: A-L reduced white blood cells (WBC) by 31.87%, lymphocyte count by 45.99%, hemoglobin by 11.72%, hematocrit by 18.56%, and platelet count by 33.08% in the NCG. Administration of various doses of UNCP increased WBC and lymphocyte count (P > 0.05) compared to the NCG. UNCP and A-L combination caused an increase in NO levels when compared to the VCG. Conclusion: Regular consumption of UNCP by guinea pigs increases plasma NO and restores some hematological disorders induced by a 3-day HD A-L administration.

Ethnopharmacological relevance Majority of people living in Ghana and many other developing countries rely on traditional medicinal plants for their primary healthcare. These plants are used either alone or in combination to manage a wide range of ailments. However, most of these plants have not been investigated for their mutagenic effects. Aim of the study This study, therefore aimed at evaluating the mutagenic activity of the most frequently used medicinal plants amongst Ghanaians living within the Accra metropolis, Ghana. Materials and methods Validated questionnaires were administered to 53 herbalists and herbal medicines dealers in the Makola, Madina and Nima communities. Plants that were identified as being frequently used were investigated for their mutagenicity using the Ames test. Results A total of 110 medicinal plants belonging to 53 families were identified as most frequently used plants in the study sites. These are used to treat various ailments including gastric ulcer, fever, malaria, male impotence, diabetes, typhoid, high blood pressure and candidiasis. Thirteen samples (52%) showed moderate to high mutagenicity in the TA 100 bacterial strain before and after metabolism with rat liver enzyme. Conclusions The study showed that over half of the frequently used medicinal plants showed moderate to high mutagenicity before and after metabolism at the concentration of a 100 μg/mL. This may have implications for the safety of those who use them to manage diseases. These findings will suggest the need for an in-depth study of the mutagenic potentials of plants commonly used by indigenous people and more especially for those exhibiting high mutagenicity in this study.

Background. There is considerable evidence that many people take dietary supplements including those of herbal origin as an alternative therapy to improve their health. One such supplement, with an amalgam of constituents, is CellGevity®. However, the effect of this dietary supplement on drug-metabolizing enzymes is poorly understood, as it has not been studied extensively. Therefore, we investigated the effect of CellGevity dietary supplement on selected rat liver microsomal cytochrome P450 (CYP) enzymes, the most common drug-metabolizing enzymes. We also determined the total antioxidant potential of this dietary supplement in vitro. Methods. To determine the antioxidant potential of CellGevity dietary supplement, 2,2-diphenyl-2-picryl-hydrazyl (DPPH), total phenolic, and flavonoid assays were used after initial preparation of a solution form of the supplement (low dose, LD; 4 mg/kg and high dose, HD; 8 mg/kg). Rats received oral administration of these doses of the supplement for 7 days, after which the effect of the supplement on selected liver CYP enzymes was assessed using probe substrates and spectroscopic and high-performance liquid chromatographic methods. Rats which received daily administration of 80 mg/kg of phenobarbitone and distilled water served as positive and negative controls, respectively. Results. The IC50 value of the supplement 0.34 ± 0.07 mg/ml compared to 0.076±0.03 mg/ml of the BHT (positive control). The total phenolic content of the supplement at a concentration of 2.5 mg/ml was 34.97 g gallic acid equivalent (GAE)/100 g while its total flavonoid content at a concentration of 2.5 mg/ml was 6 g quercetin equivalent (QE)/100 g. The supplement significantly inhibited rat CYP2B1/2B2 (LDT 92.4%; HDT 100%), CYP3A4 (LDT 81.2%; HDT 71.7%), and CYP2C9 (LDT 21.7%; HDT 28.5%) while it had no significant inhibitory effect on CYPs 1A1/1A2, CYP1A2, and CYP2D6. Conclusion. CellGevity dietary supplement possesses moderate antioxidant activity in vitro and has an inhibitory effect on selected rat liver CYP enzymes, suggesting its potential interaction with drugs metabolized by CYP enzymes.

Trichilia monadelpha is a common medicinal plant used traditionally in treating central nervous system conditions such as epilepsy, depression, pain, and psychosis. In this study, the antidepressant-like effect of crude extracts of the stem bark of T. monadelpha was investigated using two classical murine models, forced swimming test (FST) and tail suspension test (TST). The extracts, petroleum ether, ethyl acetate, and hydroethanolic extracts (30–300 mg/kg, p.o.), standard drug (imipramine; fluoxetine, 3–30 mg/kg, p.o.), and saline (vehicle) were given to mice one hour prior to the acute study. In a separate experiment the components (flavonoids, saponins, alkaloids, tannins, and terpenoids; 30–300 mg/kg, p.o.) from the most efficacious extract fraction were screened to ascertain which components possessed the antidepressant effect. All the extracts and components significantly induced a decline in immobility in the FST and TST, indicative of an antidepressant-like activity. The extracts and some components showed increase in swimming and climbing in the FST as well as a significant enhancement in swinging and/or curling scores in the TST, suggesting a possible involvement of monoaminergic and/or opioidergic activity. This study reveals the antidepressant-like potential of the stem bark extracts and components of T. monadelpha.

Two samples, water extract and blended whole leaves, of freshKalanchoe integraleaves (Crassulaceae), a traditional antihypertensive medicine used in Ghana, were analyzed with Energy Dispersive X-Ray Fluorescence spectroscopy (EDXRF). Analysis revealed 12 macro and 26 micro elements in both extracts. Further quantitative assessment of the results for amounts of elements that are pharmacologically significant revealed that the amounts of calcium, potassium, and magnesium present in the extracts could be correlated to its traditional usage in managing hypertension and arrhythmias. However, heavy metals (lead and inorganic arsenic) detected in the extracts may pose a threat at doses normally used traditionally for the treatment of hypertension.

Polyhexamethylene guanidine hydrochloride (PHMGH) is used worldwide as an antimicrobial agent with broad spectra of activity and also for treating pool water. This non-GLP preliminary study aims at investigating in a subchronic toxicity study possible effects at supra-optimal doses of this biocide. Both acute and subchronic toxicity studies were conducted. LD50 for PHMGH was estimated to be 600 mg/kg (ie LC50 2 ml of 7.5% solution) when administered as a single dose by gavage via a stomach tube in accordance with the expected route of administration. The acute studies showed that the median lethal dose (LD50) of 600 mg/kg was accompanied by signs of neurotoxicity. Haematological and biochemical parameters of subchronic toxicity studies were non-significant. Subchronic doses of 0.006 mg/kg, 0.012 mg/kg and 0.036 mg/kg were administered. 20% of the animals at a dose of 0.006 mg/kg and 0.036 mg/kg showed mild degrees of hydropic changes in proximal tubules while 10% of animals at all the doses had their liver tissues showing local areas of mild pericentral hepatocytes degeneration. PHMGH did not produce any major organ defect with regard to the kidney, heart, and liver. The LD50 was much higher than the recommended dosage by a factor of about 50,000. The recommended residual concentration is far less than the median lethal dose using rats as test subjects. These results could serve as a basis for investigating the full toxicological profile if it is to be used for the treatment of raw water to make it potable.

Kalanchoe intergra (Ki) leaf extract is an orally administered multipurpose plant medicine in Ghana and other parts of the world for the treatment of ulcers, pain and adenoma of the prostate gland. There is paucity of information concerning its short-term usage. The present study is aimed at conducting histopathological and biochemical studies in a 14-day sub-acute toxicity studies using female Sprague-Dawley rats.Crude extract of Ki leaves was prepared and freeze-dried. A 14-day sub-acute toxicity studies was conducted using 2 week old nulliparous and non-pregnant female Sprague-Dawley rats (120-150g). Reconstituted Ki was administered at a dosage of 900mgkg(-1) (high dose), 300mgkg(-1) with a control group receiving an equivalent volume of distilled water (as vehicle) by gastric lavage. Histopathological studies of major organs and blood chemistry analysis were performed on blood obtained via cardiac puncture into EDTA tubes after euthanisation.There was a significant decrease in urea (p0.016) and creatinine levels (p0.001) in both the high and low dose groups. There was an increase in ALP levels (P=0.01) in both the high and low dose groups. ALT and AST rather decreased significantly in both the high and low dose groups (p0.0001). Histopathological results did not show any abnormalities in all the HE stained paraffin sections. Thus the photomicrographs of the liver, kidney and heart were within histopathological limits.Ki leaf extract is non-toxic when administered by the oral route over a time period of 14 days at the above doses.

Objective: Kalanchoe integra is known to possess antihistaminic and mast cell stabilizing effect. Inflammatory mediators, such as histamine and eicosanoids have been implicated in the pathophysiology of allergen-induced asthma including bronchospasm, vasodilation, increased vascular permeability, perivascular and peribronchial oedema, acute functional changes in the lungs and diarrhea due to increased intestinal motility. This study is to Original Research Article European Journal of Medicinal Plants, 4(5): 542-562, 2014 543 ascertain the anti-inflammatory effect of Kalanchoe integra aqueous leaf extract (KILE) on bronchial hyper-responsiveness in ovalbumin-sensitized guinea-pigs. Method: Bronchial asthma was induced in guinea pigs using Ovalbumin. In vivo skin tests were carried out on all guinea pigs using ovalbumin and histamine as allergens. The diameters of wheals were recorded and the means determined. OA-sensitized guineapigs were challenged with 2% OA aerosols after 1 hour per os of drugs (KILE or prednisolonefor the treated groups) for two weeks. A piece of excised trachea was suspended in a tissue bath and challenged with histamine in the presence and absence of KILE, as well as Prednisolone (2.5 mg/kg). The results were reported as mean ±S.E.M. Statistical analysis was performed using one-way ANOVA and Bonferroni’s post hoc test. Results: Biological assaying of KILE showed significant dose-dependent reduction in histamine induced vasodilation of cutaneal blood vessels (P

Background: Kalanchoe integra is widely used in folklore medicine as an antiasthmaticagent. Previous studies have shown the ameliorating effect of Kalanchoe integra leaf extract [KILE] on bronchial hyperesponsiveness and inflammation.Further, the stabilizing effect of Kalanchoe sp on mast cell degranulation,suggests that Kalanchoe species are suitable candidates for allergicasthma therapy. This study is designed to investigate the anti-asthmaticpotential of KILE and monitor the accompanying histopathological andimmunobiochemical changes that occur in an animal model of bronchial asthmausing ovalbumin sensitized guinea pigs. Method: Thirty male guinea pigs weredivided into five groups of six animals each. Bronchial asthma was simulated inguinea pigs using ovalbumin. Both low dose (300 mg/kg) and high dose extract(900 mg/kg) were administered daily for 42 days. Prednisolone (2.5 mg/kg) wasthe standard drug used. Results: Guinea pigs in all KILE treated groups maintained the integrity of their airwaystructures: bronchial folds and walls, alveoli, alveolar ductsand sacs. KILE and prednisolone caused a reduction in immune parameters (p 0.001), extent of bronchoconstriction, bronchialwall thickness and goblet cell accumulation in the sensitized guineapigs. Conclusion: This study demonstrates the anti-asthmatic potential of KILE duringprolonged administration by the oral route.