Subchronic Test Research Articles

Toxicological profile of Balanites agyptiaca in albino Wistar rats

Background: Balanites aegyptiaca (BAE) is a thorny tree that grows in most arid and semi-arid areas of Africa, the Middle East and India. It is used in traditional medicine for its cardioprotective, deworming, antihelmintic, anti-infectious and antifungal properties. Excessive consumption of this plant's products can present risks of intoxication for consumers. Objective: The aim of this study was to assess the acute and subchronic oral toxicity of the aqueous extract of Balanites aegyptiaca leaves and roots, with a view to ensuring the safety of consumers of this plant. Method: Acute toxicity was carried out in accordance with the OECD experimental protocol. The plant extract tested was administered orally to female rats at a single dose of 2000 mg/kg. These animals were observed for 14 days. For the subchronic toxicity study, the aqueous extract was administered daily orally to male and female rats at different doses (250, 500 and 1000 mg/kg) for 30 days. After the treatment period, the animals were sacrificed for hematological, biochemical and histopathological analyses. Results: The results of the acute oral toxicity test showed that the aqueous extract of Balanites aegyptiaca leaves and roots was non-toxic at a dose of 2000 mg/kg. During the sub-chronic test period, observation of rat signs and behaviour revealed no abnormalities in the groups of animals treated with the extract compared with controls. A significant variation in relative heart and liver weights was observed at 1000 mg/kg. In addition, there was a significant reduction in concentrations of aspartate aminotransferase, total cholesterol, triglycerides and low-density lipoproteins in these rats. Compared with control groups. There was also a significant decrease in hemoglobin and mean corpuscular hemoglobin, with an increase in lymphocytes and white blood cells at the same dose of 1000mg/kg. Histological examinations of the kidneys and liver showed normal renal architecture, and the liver also showed normal hepatic architecture with slight degeneration at a dose of 1000mg/kg of the extract tested. Conclusion: Single administration of the 2000 mg/kg dose did not induce signs of significant toxicity in rats. However, in long-term oral treatment, safety measures must be taken. Thus, sub-chronic oral exposure of BAE to lower doses is recommended, while higher doses, of the order of 1000 mg/kg, should be avoided.

Toxicological evaluation of porcine bile powder in Kunming mice and Sprague-Dawley rats.

Background: Porcine bile powder (PBP) is a traditional Chinese medicine that has been used for centuries in various therapeutic applications. However, PBP has not previously undergone comprehensive component analysis and not been evaluated for safety through standard in vivo toxicological studies. Methods: In our study, we characterized the component of PBP by liquid chromatography-mass spectrometry. The acute and subchronic oral toxicity, genotoxicity, and teratogenicity studies of PBP were designed and conducted in Kunming mice and Sprague-Dawley (SD) rats. Results: The chemical analysis of PBP showed that the main components of PBP were bile acids (BAs), especially glycochenodeoxycholic acid. There were no signs of toxicity observed in the acute oral test and the subchronic test. In the genotoxicity tests, no positive results were observed in the bacterial reverse mutation test. Additionally, in the mammalian micronucleus test and mouse spermatocyte chromosomal aberration test, no abnormal chromosomes were observed. In the teratogenicity test, no abnormal fetal development was observed. Conclusion: Our findings demonstrate that PBP, composed mainly of BAs, is non-toxic and safe based on the conditions tested in this study.

Zidovudine reduces ketamine-induced psychotic symptoms in mice

Introduction: Infection with human immuno-deficiency virus (HIV) is associated with several neurological disorders including psychotic symptoms. Treatment or therapeutic management of these symptoms with conventional anti-psychotic drugs (APDs) is associated with drug-drug interaction and side effects that may cause treatment failure. Zidovudine (AZT) an anti-retroviral (ARV) drug, is a nucleoside analogue reverse transcriptase inhibitor (NRTI) with highest CNS penetrating ability, but few or nothing is known about its CNS effects.
 Objective of study: To evaluate the effect of AZT on ketamine-induced depression, hyperkinesia, and cognitive function in mice.
 Method: Acute toxicity was conducted for oral and intraperitoneal administration using Lorke’s (1983) method. Acute zidovudine alone and its concurrent (AZT + Ketamine) sub-chronic (7 days) administration was investigated using forced swim test, open field locomotor test and Y-maze test. Olanzepine (5mg/kg), Haloperidol (1 mg/kg) and Eserine (0.03 mg/kg) were used as standard controls respectively with saline as normal control. Eserine was administered intraperitoneal 30 minutes before the test, while the 5 tested zidovudine doses (12.5, 25, 50, 100 and 200 mg/kg) were administered singly orally for 60 minutes prior to the acute test while ketamine 30mg/kg intraperitoneal administered concurrently for 7 days for the sub-chronic test
 Result: The LD50 for oral and intraperitoneal administration were determined to be 3807.88 mg/kg and 2154 mg/kg respectively. Concurrent AZT administration with ketamine for 7 days, significantly (p<0.001) reduced immobility time at AZT doses of 25 mg/kg and 12.5 mg/kg compared to the control. The 7-days AZT concurrent treatments with ketamine reduced locomotion at all AZT test groups, compared to normal control group. The mean percent alternation was severely reduced in acute AZT treatments, but increased in concurrent AZT-ketamine administration.
 Conclusion: AZT ameliorate ketamine-induced psychotic-like symptoms in mice, but was found to cause cognitive deficits in normal controls.

Ammodaucus leucotrichus Acts as an Antihypertensive and Vasorelaxant Agent Through sGC and Prostaglandin Synthesis Pathways.

Ammodaucus leucotrichus is a medicinal plant used in traditional medicine to treat various ailments, including hypertension. The study aimed to determine the antihypertensive activity of Ammodaucus leucotrichus. The study aimed to investigate the antihypertensive and vasorelaxant activities of the aqueous extract of Ammodaucus leucotrichus fruits (ALAE) in rats. ALAE was prepared to study its antihypertensive effect in L-NAME (Nω-L-arginine methyl ester)-induced hypertensive rats and its vasorelaxant activity in isolated thoracic aortas of rats. The acute and subchronic effects of ALAE on systolic, diastolic, mean arterial pressure, and heart rate (HR) were evaluated after oral administration of ALAE (60 and 100 mg/kg body weight) for 6 h for the acute experiment and over 7 days for the subchronic test. Isolated thoracic aortic rings were prepared to examine the vasorelaxant action of ALAE. Several common pharmacological agents were used to test potential pathways implicated in vasorelaxant action. The results showed that ALAE reduced blood pressure parameters (systolic, mean, and diastolic blood pressure) in L-NAME-induced hypertension rats after repeated oral treatment over seven days without affecting normotensive rats. Furthermore, in thoracic aortic rings pre-contracted with epinephrine (EP) (10 μM) or KCl (80 mM), ALAE (0.250-1.625 mg/ml) showed a vasorelaxant effect. In isolated rat thoracic aortas, blockage of soluble guanylyl cyslase with blue methylene (P < 0.01) partially decreased this vasorelaxant effect. In addition, blockage of the prostaglandin synthesis pathway with indomethacin (P<0.05) also reduced the vasorelaxant activity of ALAE. Pretreatment of aortic rings with glibenclamide, propanolol, L-NAME, MLN-4760, or nifedipine did not affect ALAE-induced vasorelaxation. Ammodaucus leucotrichus is a prescient medicinal plant, able to act as an antihypertensive agent. Moreover, the results suggest that the extract increased cGMP in NO-independent manner.

Effects of chlorantraniliprole-based pesticide on transcriptional response and gut microbiota of the crucian carp, Carassius carassius

Chlorantraniliprole (CAP) is a presentative diamide pesticide utilized in agricultural area and as well as rice-fish co-culture system for pest control. However, the understanding of toxic effects of CAP on fish species is still incomplete. In the present study, we performed an integrated study of the acute toxicity and bioaccumulation of CAP on the crucian carp, Carassius carassius, a fish species widely distributed in freshwater area in China and commonly farmed in the rice-fish co-culture systems. Besides, biochemical changes, transcriptional responses and gut microbiota of fish were investigated upon sub-chronic CAP exposure. The results showed that CAP is low toxic to crucian carp with a 96 h LC50 of 74.824 mg/L, but has considerable accumulation in the fish muscles when exposed to 3 mg/L of CAP for 14 d and still detectable after 18 d recovery in fresh water. For sub-chronic test, fish were exposed to CAP at 0, 0.3, 3 and 30 mg/L respectively for 14 d. CAP induced oxidative stress and detoxification inhibition in the liver of fish by decreasing antioxidative and detoxicated enzymes activities and downregulating relevant genes expression. In addition, disrupted gut flora composition was found in all experimental groups by the 16 S rRNA sequencing data, indicating the gut microbiota dysbiosis in crucian carp and potential adverse host effect. All the results suggest that CAP at sublethal concentrations has prominent toxic effect on crucian carp and more attentions should be paid especially using directly in an integrated aquaculture system.

Evaluation of acute and sub-chronic oral toxicities of Neoneaster in rats.

Jaundice is a condition caused by the elevation of bilirubin level in the blood. Due to the neurological and neurodevelopmental sequalae of jaundice in newborns, the high cost of the treatment, and the side effects of the currently used therapies, novel therapeutically approaches are needed. Purgative manna (Shir-e-Khesht) has been used in Persian traditional medicine to reduce serum bilirubin levels of neonates. Neoneaster® is a natural health product formulated by a unique method from the manna of Cotoneaster nummularius Fisch. & C.A.Mey. for treating neonatal jaundice and managing constipation. The main component of Neoneaster®, mannitol, is an osmotic laxative which could increase intestinal transit and reduce the re-absorption of bilirubin in the enterohepatic cycle. We conducted this study to investigate acute and sub-chronic oral toxicities of Neoneaster in Wistar rats. In the acute oral toxicity test, based on OECD 423 we administered Neoneaster to the Wistar rats at doses of 5, 50, 300, and 2000mg/kg(OECD, 2002). Toxicological effects, including mortality and behavioral changes, were recorded for 14 days and compared to the control group. We also carried out histopathological assessments of the tissues of liver, heart, kidney, and spleen after this period. To evaluate sub-chronic toxicity, while administering 2000mg/kg of Neoneaster daily to the Wistar rats, we recorded for changes in mortality and behavior for 45 days and compared these to the values of the control group. We also carried out biochemical, hematological, and histopathological assessments after this period. In both acute and sub-chronic oral toxicity tests, no mortalities, behavioral abnormalities, and histological signs of toxicity was observed in any of the administered doses in comparison to the control group. The percentage of weight gains in acute toxicity test and the weight gain in sub-chronic test were not significant (P>0/05). There were also no significant differences in hematological and biochemical markers (P>0/05). Based on our finding, Neoneaster can be classified as category 5 in the Globally Harmonized Chemical Classification and Labeling System (GHS) as its Lethal Dose 50 (LD50) is higher than 2000mg/kg. This study suggests that Neoneaster is safe and can be classified as category 5 in the GHS system.

Study of the Antihypertensive and Vasorelaxant Activities of Haloxylon scoparium in Rats.

The work aimed to study the antihypertensive ability of Haloxylon scoparium. Haloxylon scoparium Pomel is used to treat various diseases, including hypertension. This study aimed to evaluate the antihypertensive effect of Haloxylon scoparium (H. scoparium) in hypertensive rats, and to evaluate its probable vasorelaxant activity. The aqueous extract of Haloxylon scoparium (AEHS) was prepared and used to investigate its antihypertensive ability in L-NAME(Nω-L-arginine methyl ester)-induced hypertensive rats, and its vasorelaxant activity was studied on the isolated thoracic aorta of rats. The acute and subchronic effects of (AEHS) on blood pressure parameters were evaluated after oral administration of AEHS (60 and 100 mg/kg body weight) for 6 h for the acute experiment and for 7 days for the subchronic test. The results indicated that AEHS decreased blood pressure parameters (systolic, mean, and diastolic blood pressure) after repeated oral administration in hypertensive rats without affecting normal rats. In addition, AEHS (375-1250 μg/mL) revealed a vasorelaxant effect in thoracic aortic rings precontracted with norepinephrine (NE) (10 μM) or KCl (80 mM). This effect was partially decreased in the presence of nifedipine by inhibition of the vascular calcium channel pathway in isolated rat thoracic aorta. The study demonstrates the beneficial effect of Haloxylon scoparium as an antihypertensive agent. Moreover, this plant exerts vasorelaxant activity via the blockade of Ca2+ channels.

Prolonged darkness attenuates imidacloprid toxicity through the brain-gut-microbiome axis in zebrafish, Danio rerio

The present study investigated the toxic effects of IMI on brain and gut of zebrafish (Danio rerio) by a combination of transcriptome and microbiome analysis. In addition, the involvement of light/dark period was also evaluated. An acute toxic test was conducted on adult zebrafish weighing 0.45 ± 0.02 g with 4 experimental groups (n = 15): 1) IMI group (Light: Dark = 12: 12 h), 2) prolonged light group (Light: Dark = 20: 4 h), 3) prolonged darkness group (Light: Dark = 4: 20 h) which received 20 mg/L of IMI, and 4) control group, which was not treated with IMI (Light: Dark = 12: 12 h). The results showed that prolonged darkness improved the survival rate of zebrafish upon IMI exposure for 96 h. In the sub-chronic test, zebrafish were divided into the same 4 groups and exposed to IMI at 1 mg/L for 14 d (n = 30). The results showed that IMI induced oxidative stress in both IMI and prolonged light groups by inhibition of antioxidant activities and accumulation of oxidative products. Transcriptome analysis revealed a compromise of antioxidation and tryptophan metabolism pathways under IMI exposure. Several genes encoding rate-limiting enzymes in serotonin and melatonin synthesis were all inhibited in both IMI and LL groups. Meanwhile, significant decrease (P < 0.5) of serotonin and melatonin levels was observed. However, there's remarkable improvement of biochemical and transcriptional status in prolonged darkness group. In addition, microbiome analysis showed great alteration of gut bacterial community structure and inhibition of tryptophan metabolism pathway. Similarly, the gut microbiota dysbiosis induced by IMI was alleviated in prolonged darkness. In summary, sub-chronic IMI exposure induced neurotoxicity and gut toxicity in zebrafish by oxidative stress and impaired the brain-gut-axis through tryptophan metabolism perturbation. Prolonged darkness could effectively attenuate the IMI toxicity probably through maintaining a normal tryptophan metabolism.

Biochemical Impact of Carica Papaya (Pawpaw) leaves Extract and Ruzu Bitters on Hematology and Brain Histology in Sprague Dawley Rats

Plant-based products have been utilized for nutritional and medicinal purposes for decades. Although the reported benefits of &lt;em&gt;Carica papaya &lt;/em&gt;(Pawpaw) leave extract, its role in hematology, brain histology, and the possible side effect are still areas of research deliberation. Thirty (30) male Sprague Dawley rats, divided into three groups, were fed on rat chow and normal saline, &lt;em&gt;Carica papaya &lt;/em&gt;leaves extract and Ruzu bitters, respectively. Blood chemistry, hematology, and brain histology were assayed to ascertain their effects on brain structure and biochemical changes. White blood cells, hemoglobin, red blood cells, platelets, and packed cell volume were carefully evaluated. In the sub-chronic test, there were no significant changes in PCV (%) in the papaya extract and Ruzu bitters group, relative to the control. There was a significant increase in hemoglobin levels in the papaya and Ruzu bitters groups. &lt;em&gt;Carica papaya &lt;/em&gt;leaves extract and Ruzu bitters significantly increased certain serum biochemistry parameters (&lt;em&gt;p &lt;/em&gt;&lt; 0.05), compared to the control group. Our study revealed that &lt;em&gt;C. papaya&lt;/em&gt; leaves extract possess an immunomodulatory effect and did not show any detrimental effect on the brain histology, liver, and general well-being, unlike Ruzu bitters. The neuroprotective effect of the extract is apparent from the intact brain structure of treated rats compared to the other group, (&lt;em&gt;p &lt;/em&gt;&lt; 0.05). The hydro-ethanol leaf extract of &lt;em&gt;Carica papaya &lt;/em&gt;possesses neuroprotective, anti-inflammatory, anti-hemolytic and immunomodulatory effects compared to the Ruzu bitters. However, both extracts’ long-term administration should be taken cautiously and further investigated.

Acute and subchronic toxicity profile of methanol extract of leaves of Fimbristylis miliacea (L.) Vahl.

Fimbristylis miliacea (L.) Vahl (Cyperaceae) is a grass like herb habitually breeds as weed in paddy fields and mostly disseminated in tropical or sub-tropical countries of south and south-east Asia, northern Australia, and west Africa. The plant has been traditionally used to treat fever as a form of poultice. However, no scientific study regarding its toxicity profile has been testified. The study has been carried out to determine the potential toxicity of the methanol extract from leaves of the Fimbristylis miliacea, employing the technique of acute and subchronic oral administration in mice. In the acute toxicity study according to OECD guideline 425, oral administration of FM methanol extract at single doses of 2000 and 5000mg/kg in both sexes of Swiss albino mice was performed. Toxic symptoms, abnormal behavior, changes in body weight, and mortality were observed for 14 consecutive days. In subchronic toxicity study according to OECD guideline 407, plant extract was administered orally at doses of 100, 500, 1000, and 2000mg/kg daily for 28 days. The general toxic symptoms, abnormal behavior, changes in body weight were observed daily. Biochemical analysis of serum, and histopathological examination of liver were performed at the end of the study. No mortality, abnormal behavior and urination, changes in sleep, food intake, adverse effect, and non-linearity in body weight have been recorded during acute toxicity study at the doses of 2000 and 5000mg/kg. Also, in subchronic toxicity study, FM extract produced no mortality or any kind of adverse effects in regards of general behavior, body weight, urination, sleeping routine, and food intake. In case of analysis of thirteen different biochemical parameters, concentrations of aspartate transaminase (AST) and glucose were altered significantly in male and female mice in both acute and subchronic study. Total cholesterol and triglycerides at 5000mg/kg.bw were changed in male mice in acute toxicity study. On the other hand, female mice had altered triglycerides in subchronic test. All other critical parameters were found unaffected. In subchronic test, histopathological examination of liver demonstrated cellular necrosis at 2000mg/kg.bw in both male and female mice while minor necrosis was observed at 1000mg/kg.bw. Thus, the no observed adverse effect level (NOAEL) can be assumed around 1000mg/kg.bw. The present study suggests that treatment with FM extract does not reveal significant toxicity.

Antihyperglycemic effect of aqueous extract of Tetraclinis articulata in streptozotocin-induced diabetic rats and acute toxicity analysis.

The study aimed to evaluate the glucose-lowering effect of Tetraclinis articulata. Tetraclinis articulata is commonly used for the treatment of diabetes characterized by chronic hyperglycemia. This work aimed to evaluate the effect of Tetraclinis articulata (T. articulata) aqueous extract (TAAE) on glycaemia and lipid profile in normal and streptozotocin(STZ)-induced diabetic rats. Additionally, its acute toxicity, phytochemical composition, and antioxidant capacity were assessed. To highlight the effect of TAAE on plasma glucose levels and lipid metabolism, blood glucose levels were measured at 1, 2, 4, and 6 hours of treatment for the acute test and on days 2, 4 and 7 over the daily oral administration for the subchronic test at two selected doses (10 mg/kg and 20 mg/kg). Furthermore, Triglycerides (TGs), total cholesterol (TC), and High-density lipoprotein cholesterol (HDL-c) were measured after the treatment. The rats' liver, extensor digitorum longus (EDL), and soleus muscle were isolated from diabetic rats treated with TAAE at a dose of 20 mg/kg at the end of the experiment to measure glycogen content using a standard method. The acute toxicity of TAAE was examined according to the OECD guideline. In addition, body weight, signs of toxicity, and/or mortality were observed for 14 days. Besides, a preliminary phytochemical screening, quantification of phenolic, flavonoid, and tannin contents as well as the antioxidant activity were evaluated. The results showed that TAAE at the doses of 10 and 20 mg/kg possesses a potent antihyperglycemic effect in STZ-treated diabetic rats and an acute hypoglycemic effect in normal rats, as well as, the extract provoked a decrease of blood glucose levels after glucose loading in the glucose tolerance test in a dose-dependent manner. TAAE at a dose of 20 mg/kg revealed a significant improvement of the lipid profile. However, treatment with TAAE at a dose of 20 mg/kg did not significantly modify the glycogen content. In the same way, the acute toxicity analysis revealed no death or signs of toxicity in rats, and the LD50 value was more than 2 g/kg. In addition, preliminary phytochemical screening revealed that TAAE revealed the presence of polyphenols, flavonoids, tannins, carbohydrates, saponins, quinones, sterols and terpenoids. Furthermore, TAAE exhibited a potent antioxidant activity which may be due to the richness in polyphenol content (756.21±6.72 mg GAE/1 g of extract). The current study demonstrates for the first time that aqueous Tetraclinis articulata extract has a potent the glucose-lowering effect.

Toxicity evaluation of the arils of the fruit of Blighia sapida KD Koenig (Sapindaceae) in Wistar rats

The Methanol extract of the arils of fruits of Blighia sapida was studied for its toxic effects on certain hematological and biochemical indices as well as the histopathological examination of some organs of the Wistar rats. Preliminary phytochemical screening showed that the plant contains bioactive compounds such as alkaloids, flavonoids, polyphenols, cardiac glycosides, cyanogenic glycosides, steroid glycosides, cardenolides, terpenes and tannins. Three different concentrations of the extract were administered to different groups of the rats orally for 28 days in the sub-acute test and 90 days in the case of the Sub-chronic test. The extract showed no mortality even at a dose of 5000mg/kg. Other results obtained showed a significant increase in some hematological indices such as pack cell volume (PCV), hemoglobin (Hb), red blood cell (RBC), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH). Others are mean corpuscular hemoglobin concentration (MCHC), hematocrit (HCT), and lymphocytes (LYMP). However, white blood cells (WBC) and platelets (PLT) showed a significant decrease as the doses administered increased from low to high. There was also, a significant decrease in the levels of certain biochemical indices such as urea, creatinine, total bilirubin, conjugated bilirubin, alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) while the levels potassium (K+), chloride (Cl-), total protein and albumin were significantly increased. The methanol extract of the arils of fruits of Blighia sapida revealed mild distortion of hepatocytes, loose nuclei within the cells, and also complete loss of sinusoid with an increase in dose within the liver.

Maerua angolensis DC: evaluation of the oral acute and sub-chronic toxicity profile of its freeze-dried leaves infusion extract

Maerua angolensis is a shrub/small tree that grows up to about 10 m tall. The plant is widely distributed in tropical Africa and used in various ethnomedicinal applications across the region. The objective of this study is to investigate the oral safety profile of the infusion extract of Maerua angolensis (IEMa) in laboratory animals. Hippocratic screening was adopted to evaluate the acute toxicity profile using 2000 mg/kg of IEMa, p.o. in mice. The sub-chronic toxicity was performed by daily oral administration of IEMa (800 mg/kg) in Wistar rats for 28 days and clinical observations and toxicological related parameters were recorded. After the treatment period, blood was collected for hematological and biochemical analysis, and organs were removed for macroscopic analysis. The agent exhibited mild symptoms and no mortality recorded in the Hippocratic screening. In the sub-chronic test, few changes in urine output, platelets counts and alkaline phosphatase were observed, but are within the physiological ranges for this animal specie. The results shows that IEMa does not present oral toxicity thereby displaying a wide safety margin for therapeutic use.

Sub-Chronic Toxicity Evaluation of Tannery Waste Water to Clarias gariepinus Juveniles

This paper was conducted to investigate the sub-chronic toxicity of tannery effluents sourced from Challawa industrial estate Kano, Nigeria using Clarias gariepinus. The study covered physicochemical parameters, haematological, and biochemical stress enzymes assessments. The water quality results revealed mean value of Temperature (29.92±1.93oC), pH (8.14±0.85), DO (1.60±0.38mg/l), BOD (0.77±0.16mg/l), Salinity (7.75±0.60mg/l), Nitrate (1.19 ± 0.05mg/l) and Phosphate (16.48±0.85mg/l). After termination of 21 days sub-chronic test, haematological and biochemical changes analysed were generally considered significantly different (P&lt;0.05) within the treatments. The haematological indices revealed a decrease and sudden increase in concentration of estimated values of PCV, Hb, RBC, MCHC and MCH, while WBC and MCV fluctuated. These may be attributed to stress, the duration of exposure and levels of pollutants in the effluent. Furthermore, oxidative stress enzymes followed an order of SOD &gt; CAT &gt; GSH. This could be due to level of pollutants in the effluent. The results of the data indicated tannery effluent to have a toxic effect on the experimented organism. The information calls for a more enrich toxicity testing that should involve wide range of organisms. It should entail reproductive aspects of the species, detail relationship and enhanced methodological procedures.

Cordia americana: Evaluation of in vitro anti-herpes simplex virus activity and in vivo toxicity of leaf extracts

Herpes simplex virus (HSV) type 1 and type 2 are responsible for causing infections whose symptoms can vary from subclinical to severe manifestations. Cordia americana is a plant used by traditional communities for the treatment of wounds and diarrhoea, as well as infections like flu and syphilis. Scientific evidence has shown that, among other biological activities, the plant possesses antiviral properties; however, the evaluation of the in vivo toxicity of preparations of this plant is still lacking. This study assessed the in vitro anti-HSV-1 and anti-HSV-2 activity of a crude extract (CE) obtained from the leaves of C. americana, as well as its aqueous (FAq) and ethyl-acetate fractions (FAc). In addition, the in vivo toxicity of the FAq was assessed. The sulforhodamine B method was performed to determine the antiviral activity and the in vivo toxicity was evaluated according to Brazilian federal regulations. The CE, FAq, and FAc demonstrated antiviral activity against HSV-1 in vitro, presenting EC50 values of 7.0±1.4, 1.5±0.35, and 7.5±3.8, respectively. The FAq also had activity against HSV-2 with an EC50 of 11.8±1.02. The toxicological study of FAq in animals showed that it had very low toxicity. No death occurred during acute or subchronic experiments, where up to 5000 mg/kg and 150 mg/kg FAq were tested respectively; and there were no signs of toxicity in the subchronic test. The results of this study, in conjunction with further studies, pave the way for a potential topical treatment for skin and mucosal diseases, such as HSV-1 and HSV-2 infections

Antihyperglycemic and Lipid Profile Effects of Salvia amarissima Ortega on Streptozocin-Induced Type 2 Diabetic Mice.

Salvia amarissima Ortega was evaluated to determinate its antihyperglycemic and lipid profile properties. Petroleum ether extract of fresh aerial parts of S. amarissima (PEfAPSa) and a secondary fraction (F6Sa) were evaluated to determine their antihyperglycemic activity in streptozo-cin-induced diabetic (STID) mice, in oral tolerance tests of sucrose, starch, and glucose (OSTT, OStTT, and OGTT, respectively), in terms of glycated hemoglobin (HbA1c), triglycerides (TG), and high-density lipoprotein (HDL). In acute assays at doses of 50 mg/kg body weight (b.w.), PEfAPSa and F6Sa showed a reduction in hyperglycemia in STID mice, at the first and fifth hour after of treatment, respectively, and were comparable with acarbose. In the sub-chronic test, PEfAPSa and F6Sa showed a reduction of glycemia since the first week, and the effect was greater than that of the acarbose control group. In relation to HbA1c, the treatments prevented the increase in HbA1c. In the case of TG and HDL, PEfAPSa and F6Sa showed a reduction in TG and an HDL increase from the second week. OSTT and OStTT showed that PEfAPSa and F6Sa significantly lowered the postprandial peak at 1 h after loading but only in sucrose or starch such as acarbose. The results suggest that S. amarissima activity may be mediated by the inhibition of disaccharide hydrolysis, which may be associated with an α-glucosidase inhibitory effect.

Ecotoxicological investigation of cyanobacterial crude extracts to Daphniamagna under subchronic test conditions

Cyanobacterial blooms often consist of mixtures of microcystin-producing and microcystin-free species, and both can cause unpredictable effects on aquatic organisms. In this work, the subchronic effects of the cyanobacterial crude extracts (CCEs) from microcystin-producing and microcystin-free cyanobacteria with different microcystin concentrations (1, 10, and 50 μgL−1)on Daphnia magna were investigated. The life-history trait responses of D. magna to CCEs were determined based on survival, reproduction, and somatic growth. In addition, the physiological response, represented by the feeding rate of D. magna on green algae (Scenedesmussp.), after exposure to both types of crude extracts was estimated. Our results showed that both microcystin-containing (MCCE) and microcystin-free (NCCE) crude extracts insignificantly reduced survival but strongly enhanced reproduction and somatic growth of organisms. However, degradation of eggs and neonates of the gravid females exposed to CCEs was observed. In addition, the feeding rate of D. magna exposed to MCCE increased significantly, whereas no change in the feeding rate was observed for NCCE-exposed D. magna. In general, new and interesting aspects of the toxicity of MCCE and NCCE were revealed by this study, which contributes to the understanding of the toxicity of Pseudanabaena sp. extract on D. magna under bioassays.

Ruta Montana Evokes Antihypertensive Activity Through an Increase of Prostaglandins Release in L-NAME-Induced Hypertensive Rats.

The aim of the study was to experimentally investigate the antihypertensive effect of Ruta Montana. Ruta montana L. is traditionally used in Moroccan herbal medicine to treat hypertension. This study aimed to experimentally evaluate the hypotensive and vasoactive properties of this plant. The objective of the study was to evaluate the effect of the aqueous extract of Ruta Montana on blood pressure parameters in LNAME-induced hypertensive rats and to determine the vasorelaxant activity of this aqueous extract. The antihypertensive effect of the aqueous extract obtained from Ruta montana aerial parts (RMAPAE) (200 mg/kg) was evaluated in normal and anesthetized hypertensive rats. Blood pressure parameters (systolic blood pressure (SBP), mean blood pressure (MBP) and diastolic blood pressure (DBP)) and heart rate were measured using a tail-cuff and a computer-assisted monitoring device. The acute and chronic effect of RMAPAE was recorded for 6 hours for the acute experiment and for 7 days for the sub-chronic test. In the other set, the vasorelaxant effect of RMAPAE on the contractile response was observed in the isolated thoracic aorta. The results indicated that the RMAPAE extract significantly decreased SBP, MBP, DBP and heart rate in L-NAME-induced hypertensive rats. Furthermore, RMAPAE was demonstrated to induce a dose-dependent relaxation in the aorta precontracted with Epinephrine or KCl. More interestingly, this vasorelaxant activity of RMAPAE seems to be probably mediated through the prostaglandins pathway. The present study illustrates the beneficial action of Ruta montana on hypertension and supports its use as an antihypertensive agent.

Assessment of the toxicity and biochemical effects of detergent processed cassava on renal function of Wistar rats

Fufu is a major component of food in West Africa. Local cassava farmers use detergent to ferment cassava root tuber during processing into fufu. Studies have established the hazardous health effects of detergent in humans. This study was carried out to determine the median lethal toxicity of detergent-processed cassava, and assessed its effects on the renal function of male Wistar rats. Fufu with different concentrations of detergent (250, 500 and 750 g/l) were given as food twice daily to the rats for the acute toxicity study. The sub-chronic test lasted for four weeks, during which the fufu samples prepared with 10, 20, 30, 40 and 50 g/l of detergent, were separately given to five groups of five rats, respectively. The results of the acute toxicity test showed increase in mortality with corresponding increase in detergent concentration. Plasma and urine creatinine and urea concentrations of all the detergent-treated rats were significantly higher than that of the negative and positive controls. Urinalysis showed significant presence of glucose and ketone bodies, as well as, blood and protein. Renal photomicrographs showed deranged cortical structure with diffuse loss of tubules, inflammatory cells infiltrate in the interstitium. The study concluded that detergent-processed cassava has adverse effects on the structure and function of the kidneys of rats.

Subchronic toxicity test on combination of extracted Phyllanthus niruri and Centella asiatica on haematology in rats

Background: Meniran ( Phyllathus niruri ) and pegagan ( Centella asiatica ) are well-known medicinal plants in Indonesia. Uses of meniran and pegagan as herbal medicines need to be examined for their subchronic activity to assure their safety. Objective: This study aimed to evaluate subchronic effects of a combination of extracted meniran and pegagan on Wistar rats through haematological parameters (erythrocytes, haemoglobin, haematocrit, MCV, MCH, and MCHC). Methods: Animal models used were 56 male and female Wistar rats and were divided randomly into 4 groups. Group 1 received CMC-Na 1% (control group). Group 2 received extracts of meniran and pegagan (50:50 mg/kgBW). Group 3 received extracts of meniran and pegagan (250:250 mg/kgBW). Group 4 received extracts of meniran and pegagan (1250:1250 mg/kgBW). Subchronic test of meniran and pegagan was conducted by providing treatments for the Wistar rats for 28 days. Their haematological substances were analysed statistically by using one way ANOVA and Kruskal-Wallis method with confidence interval of 95% and post-hoc. Results: This study found that the haematological substances in male Wistar rats were normal and did not significantly change (p>0,05). It also showed that haemoglobin and haematocrit substances in female rats were normal and did not significantly change (p>0,05). Erythrocytes, MCV, MCH, and MCHC in female rats indicated significant change (p<0,05), but they were still in normal ranges. Conclusion: It could be concluded that administration of the combination of extracted meniran and pegagan was not toxic to haematology of the rats in all doses.