Evaluation of Acute and Sub-Acute Oral Toxicities of Momordica foetida Schumach. (Cucurbitaceae) Leaves Methanol Extract in Wistar Rats

Momordica foetida is a plant widely used in tropical Africa to manage gastroenteric diseases. Previous studies demonstrated interesting antibacterial activity against human pathogenic bacteria. However, the security or toxicity of methanol leaf extract has not been determined yet. The aim of this study was to evaluate the acute and sub-acute toxicity of the leaf extract of Momordica foetida. In the acute toxicity study, a single oral dose of 5000 mg/kg body weight was administered to rats which were observed for 14 days in order to identify signs of toxicity or death. In the sub-acute toxicity, the animals were treated with 250, 500 and 1000 mg/kg of the extract for 28 consecutive days. Body weights and behavior were noted throughout the experiment. Upon treatment, blood and urine were collected for hematological and biochemical analysis. Liver, lungs, heart, kidneys, testes and ovaries were analyzed for relative weights and histopathology. The acute toxicity study of M. foetida leaf extract revealed no signs of toxicity related to the treatment, indicating that the median-lethal-dose (LD50) value is greater than 5000 mg/Kg of body weight. In the sub-acute toxicity assay, the extract did not affect the general behavior of animals, meanwhile, it led to a significant increase in the levels of red blood cells, platelets, hemoglobin, granulocytes and Mid-Cells (MIDs). Biochemical parameters showed an increase in total cholesterol, HDL cholesterol, serum urea, serum and urinary glucose and a decrease in urinary proteins, serum creatinine, urinary urea levels, serum activities of AST, ALT and proteins levels, as well as increases in lung, spleen and ovaries relative weight were noticed, all compared to control animals. Histological analysis revealed a normal architecture of kidneys, liver, heart, lung, ovaries and testes. This study provides valuable data on the safety of per os administration of Momordica foetida leaf methanol extract that could be very useful for future assays.

Effect of sub-acute exposure to TiO_2 nanoparticles on oxidative stress and histopathological changes in Juvenile Carp (Cyprinus carpio)

Increasing application of nanotechnology highlights the need to clarify and understand nanotoxicity. Mammalian and in vitro studies have raised concerns about the toxicity of titanium dioxide nanoparticles （TiO2-NPs）, but there are limited data on ecotoxicity to aquatic organisms. In this work, the sub-acute toxicity of TiO2-NPs to carp （Cyprinus carpio） was assessed. Superoxide dismutase （SOD）, catalase （CAT） and peroxidase （POD） activities and lipid peroxidation （LPO） levels in liver, gill and brain tissues of carps varied with concentration of TiO2-NPs suspensions and exposure time （up to 8 d）. As a result, 100 and 200 mg/L TiO2-NPs caused statistically significant decrease in SOD, CAT and POD activities and significant increase in LPO levels in tissues （P 〈 0.05）, suggesting that the fish exposed to these two concentrations of TiO2-NPs suffered from the oxidative stress. The extent of depletion of antioxidant enzymes activities and the elevation of LPO in the liver was the greatest, indicating that the liver might be the most susceptible organ to TiO2-NPs exposure. In addition, carps had gill pathologies including edema and thickening of gill lamellae as well as gill filaments, and liver pathologies including necrotic and apoptosis hepatocytes after exposed to 100 and 200 mg/L TiO2-NPs for 20 d. These results indicated a potential risk from TiO2-NPs released into the aqueous environment.

Acute and sub-acute toxicities of hydroalcoholic extract of Allium affine aerial parts in rats

Objective:To assess the potential toxicity of hydroalcoholic extract of Allium affine(A.affine)aerial parts after acute and sub-acute administration in female and male Wistar rats.Methods:For acute toxicity assay,animals orally received the limit test dose of 2000 mg/kg of A.affine extract and were observed for 2 weeks.For sub-acute toxicity study,rats were orally treated with 125,250,and 500 mg/kg/day of the extract over 28 days,and hematological,biochemical,and histological evaluations were then conducted.Results:All rats were alive with normal body weight gain over 14 days,with LD50˃2000 mg/kg.No abnormality in body weight changes but significant increases in the relative weight of spleen and lung were detected after administration of the highest dose of extract for 28 days in sub-acute assay.Hematological analysis showed prominent elevations in total white blood cells in male rats and neutrophils count in female rats after exposure to 500 mg/kg of A.affine extract.In biochemical evaluations,significant increases in serum creatinine level(female rats,250 and 500 mg/kg)and in aspartate aminotransferase(male and female rate,500 mg/kg)and alanine aminotransferase(male,250 and 500 mg/kg and female,500 mg/kg)activities,however,notable decreases in serum blood glucose(male rats,125 and 500 mg/kg),triglycerides(male rats,500 mg/kg and female rates,250 mg/kg),and low-density lipoprotein cholesterol levels(male,250 mg/kg)were found.Histological examinations presented slight portal inflammation in liver tissue,moderate pneumocyte hyperplasia,congestion and peri-bronchial inflammation in lung tissue,and mild histiocytosis and lymphoid follicular activation in spleen tissue after exposure to 500 mg/kg of A.affine extract in male and female animals.Conclusions:The present investigation reveals the safety of A.affine extract at doses of lower than 250 mg/kg in rats and monitoring of lung,spleen,and liver functions is suggested during excessive and prolonged uses.

Reversal Effects of N-Acetyl Cysteine on <i>Moringa oleifera</i>Leaves-Induced Sub-Acute Hepatotoxicity in Wistar Albino Rats

Background: M. oleifera is a highly valued medicinal plant used widely from time immemorial to treat various ailments. However, with continued un-standardized use of the plant leaves, studies have reported organ toxicity to the liver, kidney and the heart. As communities continue to use M. oleifera leaves for its medicinal and nutritional values, there is need to find an antidote for its hepatotoxicity. Aim: The study established the reversal effect of N-Acetyl Cysteine (NAC) on M. oleifera aqueous leaf extract-induced hepatotoxicity in Wistar albino rats. Methods: Twenty-four (24) rats received a toxic dose (8.05 g/kg bwt) of M. oleifera leaf extract for 28 days to cause sub-acute hepatotoxicity. They were divided into 4 groups of 6 rats each. Group I received 1 ml normal (control group), Group II received 1000 ng/kg NAC, Group III received 1200 mg/kg NAC and Group IV received 1500 mg/kg NAC. Another group of 6 rats (Group V) received 0.75 mg/kg Paracetamol to cause hepatotoxicity. Group V (a positive control) received the prescribed clinical dose of 1200 mg/kg NAC which reverses the hepatotoxicity. All the NAC doses were given once a day intragastric for 7 days. On days: 1, 3 and 7 of receiving NAC, liver serum enzymes and bilirubin were measured. On day 7 the animals were sacrificed and liver tissue harvested for histopathology analysis. Results: A dose of 8.05 g/kg of M. oleifera leaf extract and 0.75 mg/kg Paracetamol were able to induce hepatotoxicity in Wister albino rats in 28 days. The M. oleifera extract induced hepatotoxic rats treated with NAC at doses of 1000 mg/kg, 1200 mg/kg and 1500 mg/kg, had a reduction in mean serum liver enzymes, plus reduced mean serum bilirubin levels. The liver histopathological analysis showed reduced inflammation after treatment with NAC for 3 and 7 days in the M. oleifera and paracetamol induced hepatotoxic rats. Conclusion: NAC can reverse M. oleifera leaf aqueous extract-induced sub-acute hepatotoxicity in Wistar Albino rats.

Role of Routine Benzodiazepin in Eliciting Classical Electroencephalogram (EEG) Response in Suspected Sub-Acute Sclerosing Panencephalitis (SSPE) Cases

Background: EEG could be normal or atypical in spite of suggestive clinical features and positive measles Ab of SSPE cases which could have typical EEG pattern after Benzodiazepine. Objectives: The purpose of the present study was to find out the necessity of administration of benzodiazepine during EEG recording of SSPE cases as well as to compare the efficacy of diazepam and midazolam in eliciting EEG pattern. Methodology: This double blind, parallel, single centered, non-randomized clinical trial was conducted in the Department of Pediatric Neurology at National Institute of Neurosciences, Dhaka, Bangladesh from July 2014 to June 2015 for a period of 1 (one) year. All the clinical and investigational suspected cases of sub-acute Sclerosing Panencephalitis (SSPE) children in both sexes were included as study population. Others neurodegenerative diseases including Wilson’s disease were excluded from this study. Patients were divided into two groups named as group A who were given diazepam and the other group B was given midazolam in IV during EEG recording. The clinical outcomes were measured and were recorded in a pre-designed data sheet. Result: The characteristic typical periodic slow wave complex (PSWC) was found only in 8 (30.8%) patients among the 26 (100.0%) before intervention with benzodiazepines. The remaining 18 (69.2%) had non-typical PSWC of which 10 (38.5%) were normal, 3 (11.5%) with atypical PSWC and 5 (19.2%) were with other EEG findings. After intervention with benzodiazepines, 23 (88.5%) had shown typical PSWC and only 3 (11.5%) had non-typical PSWC. Among the typical PSWC cases after intervention, 8 (30.8%) had normal EEG initially, 5 (19.2%) had other EEG finding, 2 (7.7%) had non-typical PSWC and 8 (30.8%) had typical PSWC from the beginning. Of the 3 (11.5%) of the non-typical PSWC of intervention group, 2 (7.7%) had shown no changes in EEG from the beginning and 1 (3.8%) had shown other EEG finding. The difference between before and after intervention was actually statistically extremely significant (p 0.05). Conclusion: The role of benzodiazepine is very obvious in eliciting the typical EEG pattern in SSPE patients which has shown the characteristic PSWC in EEG in most cases.

Acute myocardial infarction and sub-acute stent thrombosis associated with occult essential thrombocythemia

70-year-old female with no Aprevious cardiac history resented with complaints of severe chest and back pain lasting for 20 minutes. She had a past history of type 2 diabetes mellitus for five years and hypertension for twenty years, but denied a history of hyperlipidemia, smoking or hemorrhagic disorder. There was no family history of coronary artery or hematologic disease. On physical examination, the blood pressure was 145/90 mmHg and the heart rate was 102 beats/rain. Cardiac examination revealed normal S1 and $2 sounds. There were no murmors or clicks. The lungs were clear on auscultation. Hepatosplenomegaly or lymphadenopathy was not detected. Her electrocardiogram showed ST elevations in lead V1-V6, consistent with acute anterior MI and echocardiogram supported the diagnosis with a slight reduction in wall motion in the anterior region. Complete blood count revealed a white blood cell count of 9 000/mm3 with a normal differential, red blood cell count of 3.5×106/mm3, hematocrit of 40.2%, and platelet count of 238 000/mm3. Emergent coronary angiography demonstrated proximal thrombotic occlusion of the left anterior descending artery （LAD） （Figure 1A）. A loading dose of 600 mg clopidogrel and 300 mg acetylsalicylic asid （ASA） was given immediately. After administration of 10 000 U intravenous heparin, angioplasty was performed and a 3.0 mm×20.0 mm bare metal stent （BMS） was deployed to the LAD. Repeat angiogram revealed TIMI III flow in the LAD （Figure 1B）. Five days later, the patient was discharged without any bleeding or thrombotic complications. She was receiving dual antiplatelet therapy with ASA and clopidogrel 150 mg daily. However, she was admitted to our hospital again with severe chest pain just one day after dischargement. Her platelet count of 487 000/mm3 was remarkable in comparison with her previous complete blood count. Electrocardiogram showed ST elevations in leads V1-V6, suggestive of an acute anterior reinfarction. Coronary angiography revealed in- stent thrombosis in the LAD （Figure 1C）. After balloon angioplasty （Figure 1D）, TIMI III flow was achieved and no residual stenosis was seen. During her follow-up, complete blood cell counts showed gradually increasing platelets up to 818 000/ram3, on the fourth day of sub- acute stent thrombosis. Peripheral blood smear examination was performed and showed markedly increased large thrombocytes with anisothrombia, consistent with essential thrombocythemia （ET）. Soon after, platelet-loweringtherapy with hydroxyurea （500 mg/d） was initiated, One week after the initiation of hydroxyurea, the platelet count was decreased to 220 000/ram3. The patient remained on hydroxyurea and dual antiplatelet therapy. She was free of symptoms for three months during the follow-up period and her platelet counts remained within the normal range.

Toxicological Assessment of Irvingia gabonensis Leaf Extracts in Albino Rats: A Comparative Study between Aqueous and Ethanol Extraction Methods

Background: This study aimed to assess the toxicity of Irvingia gabonensis leaf extracts in albino rats and investigate their effects on body weight, liver function parameters, and renal function parameters. The research specifically compared the outcomes of aqueous and ethanol extraction methods. Methods: Acute toxicity was evaluated by administering a single oral dose of Irvingia gabonensis leaf extracts to rats and monitoring them for 24 hours and during a 14-day observation period. Sub-acute toxicity was assessed through a 28-day administration of the leaf extract. Body weight changes, liver function parameters, and renal function parameters were measured and compared among treatment groups. Results: No signs of toxicity or mortality were observed in rats treated with Irvingia gabonensis leaf extracts obtained through either aqueous or ethanol extraction methods. The calculated lethal dose required to cause mortality in 50% of the tested animals (LD50) exceeded 5000 mg/kg body weight. Oral administration of the leaf extract at doses of 400 and 800 mg/kg body weight did not induce any observable signs of toxicity or adverse effects during the 28-day study period. Male and female albino rats treated with the leaf extract showed significant weight gains compared to the control group. Higher doses (800 mg/kg) of both aqueous and ethanol extracts led to increased levels of total protein, albumin, and globulin in male albino rats, with the ethanol extract exhibiting a more pronounced effect. The administration of the ethanol extract, particularly at the lower dose (400 mg/kg), resulted in decreased levels of liver enzymes (AST, ALT, and ALP), suggesting potential liver protective properties. Additionally, bilirubin levels, a marker of liver dysfunction, were significantly reduced in all treatment groups, with the lowest levels observed in the groups receiving higher doses of both aqueous and ethanol extracts. The administration of Irvingia gabonensis leaf extracts did not significantly affect renal function parameters in both male and female albino rats. Conclusion: Irvingia gabonensis leaf extracts obtained through aqueous and ethanol extraction methods showed no acute or sub-acute toxicity in albino rats. The extracts demonstrated potential beneficial effects on liver function parameters, particularly at higher doses. However, further research is needed to validate these findings and determine the optimal dosage for potential therapeutic applications in humans.

Infectious diseases in the aftermath of monsoon flooding in Pakistan

Pakistan is ranked 9th in terms of flood-affected countries worldwide.In the summer of 2010,the northern province of Khyber-Pakhtunkhwa received more than 312 mm of rain in a 56 hour period.This resulted in over 1 600 deaths across the region.In addition,over 14 million people were directly affected by this record-breaking deluge.Flood affected regions serve as ideal breeding grounds for pathogens,leading to the spread of diseases.The poor standards of hygiene in camps set up for individuals displaced by the floods also contribute to this.It is essential that those involved in relief efforts are aware of the epidemiology of diseases that have historically seen a sudden upsurge after natural disasters.Keeping this in mind,we conducted a simple review of literature.An extensive literature search was conducted using the PubMed data base and online search engines.Articles published in the last 20 years were considered along with some historical articles where a background was required.Seven major diseases were identified to increase substantially in the aftermath of natural disasters.They were then classified into acute and sub-acute settings.Diarrhea,skin&eye infections and leptospirosis were identified in the acute setting while malaria,leishmaniasis,respiratory infections and hepatitis were identified in the sub-acute setting.

Toxicity Profile of Karuho Poison on the Brain of Wistar Albino Rats

Various forms of Karuho poisoning are a common traditional mystery and a public health challenge in Goma city, North Kivu in DRC practiced by unscrupulous people. Its signs and symptoms are commonly mistaken by local communities and medical world with those of tuberculosis, HIV/AIDS and typhoid fever;with neurological and psychological symptoms. Study investigated sub-acute toxicity of Karuho poison on brain of Wistar albino rats. Laboratory based experimental study was conducted at Department of Pharmacology & Therapeutics, Makerere University College of Health Sciences. A total of 4 Karuho poisons (OMGKRP, DLNKRP, CHKRP and BHKRP) were screened for acute and sub-acute toxicity. Fifty animals, 10 in each group were daily dosed for 28 days with 1 mg, 5 mg, 20 mg and 5000 mg/kg bwt of OMGKRP (most active following screening) and normal saline for control group using OECD 407 and NIH 2011 guidelines. Behavioral changes were noted. Histopathological changes in brain regions were analyzed. Treated rats by OMGKRP, most active Karuho poison, were associated with sign of depression, piloerection and shortness of breath. Histopathological changes revealed moderate diffuse congestion and mononuclear inflammatory cells infiltration (plasma cells, lymphocytes and macrophage) in cerebral region with severe inflammation observed in meninges of cerebellum. OMGKRP poison induced inflammation of meninges of cerebellar region of brain.

Exacerbation of Soft Tissue Lesions in Lead Exposed Virus Infected Mice

Objective To investigate the effect of Lead (Pb) acetate exposure on Semliki forest virus (SFV) pathogenesis in mice. Methods Different doses (62.5, 125, 250 and 500 mg/Kg body weight) of Pb dissolved in normal saline were given to mice by oral intubation in a sub-acute (28 days) and sub-chronic (90 days) regimen followed by SFV infection. Morbidity, mortality, clinical symptoms, mean survival time (MST), changes in body and organ weight, accumulation of lead in soft tissues, virus titre in brain and histopathological alterations were compared between lead exposed and infected groups. Results Early appearance of virus symptoms, increased mortality, decreased MST, enhanced SFV titre and greater tissue damage were observed in lead exposed-SFV-infected mice. Conclusion Pre-exposure to lead increases the susceptibility of mice towards SFV infection. Further studies are suggested in view of the persistence of lead in the environment and the possibility of infection by microbial pathogens.

Blood Chemistry and Major Body Organ Induced-Toxicity by Locally-Made Traditional OMGKRP Karuho Poison in Wistar Albino Rats

OMGKRP is one of various Karuho poison mysteriously used by unscrupulous individuals to kill people during conflict and animals in Goma City, in DRC. The symptoms and signs of most cases are usually confused with many chronic diseases like tuberculosis and HIV/AIDS;with renal, hepatic and cardiac manifestations as well as blood chemistry changes. The study investigated the toxic effect of OMGKRP poison on blood chemistry, serum enzymes and organ toxicity including the kidney, lung, liver and heart of Wistar albino rats. A laboratory-based experimental study was conducted. Fifty animals in 5 groups each with 10 animals were dosed daily for 28 days with 1.0 mg, 5.0 mg, 20.0 mg and 5000.0 mg/Kg body weight of OMGKRP and normal saline as control group. International standard guidelines, OECD 407 and NIH 2011 were followed during the study period. The blood chemistry analysis, relative organ weight and histopathological changes in the kidney, lung, liver and heart were performed. The findings showed that OMGKRP was associated with increased blood chemistry parameters including total proteins, creatinine, urea, K+?levels, direct albumin levels, a decrease in Cl&#8722;?levels and albumin levels. Histopathological findings showed an increased relative weight and tissue damages of the lung, kidney, liver and heart. Therefore, OMGKRP Karuho poison caused toxicity on blood chemistry, serum enzymes as well as histopathological changes in the lung, renal, hepatic and cardiac tissue damages in Wistar albino rats.