Toxicity In Wistar Albino Rats Research Articles

Chitosan-TPP encapsulated quercetin nanoparticles: amplified protection mechanisms unveiled against Ethion-induced developmental toxicity through comprehensive in-vivo and in-silico elucidation.

The study investigated Ethion-induced developmental toxicity in Wistar albino rats and the potential ameliorative effects of quercetin and nano-quercetin co-administration. Further, In-silico docking of Ethion and quercetin with MCL-1 was conducted. Quercetin nanoparticles were synthesized by ionic-gelation method. The encapsulated quercetin nanoparticles were characterized for Zeta size, UV-Vis spectroscopy, encapsulation efficiency, and TEM studies. Male rats were administered Ethion (high/low dose), quercetin, and nano-quercetin alone or in combination for 60 days. Female rats were introduced for mating on the 61st day, and pregnant females were observed for 20 gestational days. On GD 20, rats were sacrificed and evaluated for body/organ weight, reproductive indices, fetal morphology, skeletal, and visceral deformities.In silico binding energies of ethion and quercetin with MCL-1 were determined. Nanoparticle size was 363.2 ± 1.23 nm on day 0 and 385.63 ± 1.53 nm on day 60, with PDI of 0.247 and charge of 22.9 mV. Absorbance maxima were at 374 nm, with encapsulation efficacy of 85.16 ± 0.33%. EHD male crossed females showed decreased body/organ weights, reduced fertility, hematoma, cleft palate, tail curling, and absence of extremity. Nano-quercetin co-administration normalized parameters comparable to controls. Both Ethion and quercetin interacted with MCL-1, with quercetin exhibiting stronger binding energy. Nano-quercetin demonstrated stronger antioxidant properties than quercetin, counteracting ethion-induced maternal/fetal abnormalities.

Metabolic profiling of Verbena bonariensis L. extract by LC/MS and evaluation of the hepatoprotective potential with isoniazid- and rifampicin-induced hepatotoxicity in rats.

The study explored the hepatoprotective activity and metabolic profile of Verbena bonariensis L. methanol extract (VBM) and fractions using isoniazid as well as rifampicin-triggered liver toxicity in Wistar albino rats. Metabolite profiling of VBM using HPLC-PDA-ESI-MS identified 12 compounds, mainly iridoids, phenylpropanoids, and flavonoids, where verbascoside represents the major compound. Different biochemical parameters such as aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP), bilirubin, and total protein levels were used to assess liver functions. All the evaluated samples exhibited hepatoprotective potential, but VBM exhibited maximum activity and a notable decline in ALP (p < 0.05, significant), even better than the standard drug (silymarin). VBM significantly reduced the elevated ALT, AST, ALP, and total bilirubin. It also triggered a significant elevation in total proteins compared with diseased animals. This was further consolidated by histopathological studies. Verbena bonariensis L. could serve as a potent hepatoprotective agent and may alleviate liver ailments.

Protective Effect of Green Chiretta (Andrographis paniculata) against Methotrexate-induced Cardio and Spleen Toxicity: In-vitro and In-vivo

Background:: Methotrexate (MTX) is a widely used medication for treating various conditions, including skin infections, inflammatory diseases, autoimmune disorders, and malignancies. However, prolonged and extreme use of MTX can lead to detrimental effects on multiple organs. Green Chiretta (GC) is a traditional medicinal plant known for its anti-inflammatory, antioxidant, and immunostimulatory properties. Objective:: The objective of this study is to examine the antioxidant potential of GC through in-vitro analysis and to assess the potential protective effects of aqueous leaf extracts of GC against MTXinduced cardiac and spleen toxicity. Methods:: In-vitro antioxidant activity was assessed by measuring total phenolic content, DPPH, catalase and peroxidase activity. We divided rats into five groups (n=6), and after the study, rats were euthanized and the levels of antioxidants (SOD, CAT &amp; GSH) and lipid peroxidase (MDA), as well as histopathology modification of the heart and spleen tissues were examined. Results:: Our study's findings highlight the superiority of the aqueous GC extract's antioxidant capacity relative to other solvents (ethanol and methanol). Moreover, the aqueous GC extract's administration to rats yielded significant progress in antioxidant levels (Superoxide dismutase, catalase, glutathione), a reduction in lipid peroxidation (MDA), and the restoration of cardiac and spleen histoarchitecture against MTX-induced toxicity. These results collectively emphasize the extract's potential as a valuable therapeutic option against oxidative stress and tissue damage. Conclusion:: The present study revealed that the aqueous GC extract demonstrated its protective efficacy against MTX-induced cardio and spleen toxicity in Wistar albino rats

Protective role of hydroxy citric acid (HCA) against lead induced toxicity in albino wistar rats

The present study was designed to evaluate the role of herbal active constituent hydroxycitric acid obtained from Garcinia cambogia and Hibiscus subdariffa in heavy metal especially lead poisoning. The Lead acetate at 500ppm was used as an inducing agent in the present study. Sodium acetate (500ppm) used as control group is used as a baseline measure. The HCA at 100 mg/kg and 200mg/kg were used in the treatment of lead induced toxicity in rats. At the end of 28 days study period the blood levels of alpha ALAD activity was estimated in all the treatment groups. Lead inhibits the ALAD is more profound and its inhibition has been used clinically to gauge the degree of lead poisoning. Inhibition of ALAD results in the accumulation of aminolaevulinic acid, detectable in the plasma and urine even at blood lead levels of less than 10 µg/dl. It results that HCA showed significant elevated levels of ALAD activity, which was reduced by the lead intoxication. HCA showed significant reduction of liver enzymes (SGOT, SGPT and ALP). The markers like protein, bilirubin and creatinine were also found to be elevated in lead intoxicated rats and was found to be decreased significantly in a concentration dependent manner.

Effects of Semaglutide in Doxorubicin-Induced Cardiac Toxicity in Wistar Albino Rats.

Doxorubicin (DOX) is used to treat various types of cancers. However, its use is restricted by cardiotoxicity, a leading cause of morbidity and mortality. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) may be associated with cardioprotective properties. This study aims to determine the protective effects of different semaglutide (SEM) doses on DOX-induced cardiotoxicity in a rat model. Thirty-five female Wistar rats were divided into five groups. The first group received distilled water as a negative control (NC); the positive control (PC) group received distilled water plus DOX; the third group (SL) received a low dose of SEM (0.06 mg/kg) plus DOX; the fourth group (SM) received a moderate dose of SEM (0.12 mg/kg) plus DOX; and the fifth group (SH) received a high dose of SEM (0.24 mg/kg) plus DOX. Blood samples were collected on day 8 to assess serum troponin, lactate dehydrogenase (LDH), creatine phosphokinase (CPK), total lipid profile, and vascular cell adhesion molecule 1 (VCAM-1). Cardiac tissue was sent for histopathological analysis. DOX increased the total cholesterol (TC), low-density lipoprotein (LDL), triglyceride (TG), LDH, and CKP levels. Moderate and high doses of semaglutide significantly reduced serum cholesterol levels (*p = 0.0199), (**p = 0.0077), respectively. A significant reduction (***p = 0.0013) in total body weight after treatment with SEM was observed in the SL group and a highly significant reduction (****p < 0.0001) was observed in the SM and SH groups. SEM at all doses reduced CPK levels. The SL group showed a significant reduction in troponin level (*p=0.0344). Serum LDH levels were reduced by all three SEM doses. The histopathological findings support the biochemical results. Semaglutide may possess cardioprotective properties against DOX-induced cardiotoxicity in a rat model by decreasing serum biochemical markers of cardiotoxicity.

Comparative Assessment of Opioid Reversal Nasal Spray Efficacy in Countering Fentanyl-Induced Opioid Toxicity in Wistar Albino Rats

Comparative Assessment of Opioid Reversal Nasal Spray Efficacy in Countering Fentanyl-Induced Opioid Toxicity in Wistar Albino Rats

Acute and Repeated Dose 28-Day Oral Toxicity Studies of Phlorotannin Rich Fraction of &lt;i&gt;Sargassum tenerrimum&lt;/i&gt;, A Marine Brown Algae

Sargassum tenerrimum is a marine brown algae rich in phlorotannins, a class of marine polyphenols with significant biological activities. The present study aimed to prepare a phlorotannin-rich fraction from S. tenerrimum (PST) and evaluate its acute and subacute oral toxicity in Wistar albino rats according to the procedures and methods of the OECD test guidelines for acute and repeated dose 28-day oral toxicity studies. S. tenerrimum powder was extracted with ethanol and further fractionated with ethylacetate, 1-butanol, and water. The ethyl acetate fraction was found to have the highest total phlorotannin concentration and was evaluated for its safety. In the acute oral toxicity study, a single dose of PST at 2000 mg/kg body weight did not result in any treatment-related clinical symptoms of toxicity or mortality. Therefore, the median lethal dose (LD50) of PST was identified as greater than 2000 mg/kg. The subacute oral toxicity investigation at 200, 400, and 800 mg/kg doses administered for 28 days with a 14-day recovery period revealed no treatment-related adverse clinical symptoms or mortality/morbidity. The treated animals exhibited normal weight gain, feed intake and did not result in clinically significant toxicity as measured by clinical blood chemistry and hematological markers. Gross and histological examinations of selected tissues did not reveal any notable adverse alterations associated with the intervention. Under the study's findings, the LD50 for PST was determined to be &gt;2000 mg/kg b.wt. and No Observed Adverse Effect Level (NOAEL) to be 800 mg/kg rat b.wt.

The protective effects of baicalin and chrysin against emamectin benzoate-induced toxicity in Wistar albino rats.

The aim of this study was to investigate the effects of baicalin, chrysin and their combinations against emamectin benzoate-induced toxicity in rats. For this purpose, sixty four rats were divided into evenly8 groups with 6-8-week-old male Wistar albino rats, weighing 180-250g, in each group. While the first group was kept as a control (corn oil), the remaining 7 groups were administered with emamectin benzoate (10mg/kg bw), baicalin (50mg/kg bw) and chrysin (50mg/kg bw) alone or together for 28days. Oxidative stress parameters, serum biochemical parameters and blood/tissue (liver, kidney, brain, testis and heart) and tissue histopathology were investigated. Compared to the control group, the emamectin benzoate-intoxicated rats had significantly higher tissue/plasma concentrations of nitric oxide(NO) and malondialdehyde(MDA), as well as lower tissue glutathione(GSH) concentrations and antioxidant enzyme activity (glutathione peroxidase/GSH-Px, glutathione reductase/GR, glutathione-S-transferase/GST, superoxide dismutase/SOD, catalase/CAT). Biochemical analysis showed that emamectin benzoate administration significantly increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) activities, as well as triglyceride, cholesterol, creatinine, uric acid and urea levels, and decreased serum total protein and albumin levels. The histopathological examination of the liver, kidney, brain, heart and testis tissues of the emamectin benzoate-intoxicated rats demonstrated necrotic changes. Baicalin and/or chrysin reversed the biochemical and histopathological alterations induced by emamectin benzoate on these tested organs. Therefore, baicalin and chrysin (alone or in combination) could offer protection against emamectin benzoate-induced toxicity.

In Vitro and In Vivo Toxicological Evaluation of Avicennia africana P: Beauv. (Avicenniaceae) Leaf Extract in a Rat Model.

Avicennia africana is an important ethnomedicinal plant that has long been used to treat malaria and several other diseases. Despite the plant's antimalarial and other therapeutic properties, there is limited evidence-based data on its potential toxicity. Hence, the purpose of the current study was to assess the safety of A. africana leaf ethanolic extract (AAE). The study was designed to ascertain the cytotoxic effects of the crude extract on red blood cells (RBCs) as well as the acute and subacute toxicity in Wistar albino rats in accordance with Organization for Economic Co-operation and Development (OECD) guidelines "Test No. 423" and CPMW/SWP/1042/99. The pulverized, shade-dried plant leaves were sequentially macerated with 70% ethanol to obtain the crude extract (AAE). The extract's cytotoxic activity (CC50) against the uninfected human red blood cells (RBCs) was determined using the 3-(4,5-Dimethylythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. For the acute toxicity studies, the rats (male and female) were divided randomly into six groups of five rats (n = 5) and dosed orally once with the following dose levels: 100, 300, 1000, 3000, and 5000 mgkg-1, p.o. of the extracted AAE, with the control group receiving only the vehicle. In the repeated dose toxicity studies, the rats (both sexes) were orally administered daily with AAE at 100, 300, and 1000 mgkg-1 for 14 days. Rat body weights were measured, and blood samples were tested for haematological and biochemical markers. Internal organs like the heart, kidney, liver, and spleen were collected, inspected, and weighed, and histological examinations were performed. The median lethal dose (LD50) value is greater than 5000 mgkg-1 body weight, with no significant change in bodyweight or relative organ weight (ROWs) of the extract-treated groups or control group. The extract showed greater cytotoxicity activity (CC50), which was >100 μg/mL, compared to the reference drug (artesunate).The dosage groups of 100 and 300 mgkg-1bwt had neutrophilia and lymphocytopenia (p < 0.05). However, changes in these haematological parameters may not be dose dependent and could be stress related. All the serum biochemical markers studied in rats given AAE did not show any significant change (p > 0.05). Histopathological examination of internal organs of AAE-treated rats did not show any significant abnormalities resulting from the extract treatment compared to the control group. Based on the findings in the present study, the LD50 value of AAE was found to exceed 5000 mgkg-1 in the acute toxicity test, while the no observed adverse effect level (NOAEL) in rats was 1000 mgkg-1 p.o. In the sub-acute toxicity tests. Histopathological analysis revealed no morphological abnormalities in the vital organs.

Phytochemical Composition and Hepatoprotective Potential of Ethanolic Root Extract of Jatropha curcas in Acetaminophen-Induced Toxicity in Albino Wistar Rats

This study evaluated the phytochemical composition and hepatoprotective potential of ethanolic root extract of Jatropha curcas in acetaminophen-induced toxicity in wistar albino rats. The phytochemical screening and composition were determined using gas chromatography. Thirty albino rats weighing between 170 and 200 g were used, were separated into 5 groups. Group one was administered distilled water, 2 was administered 1000 mg/kg AC only, 3, 4 and 5 were administered 1000 mg/kg acetaminophen + 200 mg/kg extract, 1000 mg/kg acetaminophen + 400 mg/kg extract, 1000 mg/kg AC + 100 mg/kg Silymarin. Phytochemical composition of root of the plant showed saponin (55.7079 µg/g) lunamarine (34.3976 µg/g), kaempferol (32.7107 µg/g), rutin (20.7399 µg/g), sapogenin (11.2644 µg/g), phenol (4.1557 µg/g), anthocyanin (1.1946 µg/g), epicatechin (0.8303 µg/g) and catechin (0.1883 µg/g). The plasma ALP, AST, ALT and GGT activities of the negative control were 151.50±14.11 U/L, 48.00±7.19 U/L, 79.50 ± 2.14 U/L and 3.50± 0.45 U/L respectively. The plasma ALP, AST, ALT and GGT activities of group 3 were 78.50± 4.75 U/L, 23.00± 2.35 U/L, 49.00± 3.65 and 2.95 ± 0.17 U/L respectively, were significantly decreased when compared with the controls. The plasma total protein, albumin and total bilirubin levels of the negative control were 57.00± 0.86 g/l, 32.00 ± 0.86 g/l, 20.35 ± 0.83 µmol. The plasma total protein, albumin and total bilirubin levels of group 3 were 61.50± 2.14 g/l, 33.00± 0.86 g/l 11.15 ± 0.98 µmol respectively and were significantly increased when compared the controls. The significant improvement observed on the liver markers is suggestive of the hepatoprotective properties of Jatropha curcas.

Hepatoprotective potential of the n-butanol extract of Moricandia arvensis from Algeria against doxorubicin induced toxicity in Wistar albino rats

Hepatoprotective potential of the n-butanol extract of Moricandia arvensis from Algeria against doxorubicin induced toxicity in Wistar albino rats

Impact of Resveratrol in Attenuating Cisplatin Induced Testicular Toxicity in Male adult Rats

Background and Objective: Resveratrol is a poly-hydroxyphenol plant toxin that alleviates oxidative stress by increasing endogenous antioxidant levels and prevents tissue damage. The study aimed to investigate the anti-oxidative role of Resveratrol by histochemical, ultrastructural, and biochemical methods in Cisplatin-induced testicular toxicity in Wistar Albino rats.&#x0D; Material and Methods: Quasi-experimental study was conducted at the Department of Pharmacology, Anatomy and Postgraduate Laboratory of ISRA University Hyderabad from October 2020 to March 2021. Twenty-four male, normal adult Wistar albino rats were recruited and distributed equally into; Group-A (Control), Group-B (Experimental group or Cisplatin group), Group-C (Experimental group or Cisplatin + Resveratrol combination group). Pre and post-experimental body weight, analysis of oxidative markers, semen parameters, and histomorphology were carried out in all three groups. SPSS version 24.0 was used for the analysis of Data.&#x0D; Results: A statistically significant decline in the body weight and testicular weight in group B and C respectively (p&lt;0.05). While reduction in sperm count, motility and viability was observed in Group-B compared with Group-C (p&lt;0.05). Oxidative markers were also significantly depleted in Group-B in comparison to Group-C (p&lt;0.05). Evident changes were observed in the testicular histology of Group-B compared with Group-C (p&lt;0.05). Irregular, regressive, and atrophic seminiferous tubules were seen in Group-B. Most seminiferous tubules having normal morphology were observed in Group-C while the number of atrophic and degenerative seminiferous tubules also decreased significantly. &#x0D; Conclusion: Resveratrol is a potent protective agent with promising results in attenuating cisplatin-induced oxidative stress and eventually testicular toxicity.

Protective Effects of Aloe vera Gel Ethanolic Extract Against Streptozotocin-induced Hepato-pancreatic Toxicity in Female Albino Rats

Aims: Organ toxicity results from the accumulation of toxic substances in the organs which ultimately culminates in failure of the organ. Allopathic medications are not very effective in organ protection. Hence, it is imperative that a natural and safer organoprotective agent should be found.&#x0D; Study Design: To assess the organoprotective effect of Aloe vera gel against STZ for renal, hepato and pancreatic toxicity in albino Wistar rats.&#x0D; Place and Duration of Study: Whole work had been completed at the Microbiology and Molecular biology labs of IMBB, The University of Lahore during 2019- 2020.&#x0D; Methodology: Organoprotective ability of different doses of ethanolic extracts of Aloe vera (A. vera) gel was evaluated against intraperitoneal induction of 55mg/kg Streptozotocin (STZ)-induced pancreatic, renal and hepatic toxicity in female albino Wistar rats by keeping metformin (100mg/kg) as a positive protective control.&#x0D; Results: Results revealed that 200 mg/kg ethanolic extracts of A. vera gel showed significant organoprotection as ALT (57.5±7.45I U/L), AST (39.8±3.45I U/L), ALP (438±103I U/L), urea (74.1±8.71mg/dl), creatinine (0.688±0.146 mg/dl), amylase (1247±75 U/L) and lipase (16.6±2.02 U/L) were significantly less than organotoxic control [ALT (103±7.23I U/L), AST (237±12.7I U/L), ALP (2092±195 U/L), Urea (153±18.6mg/dl), Creatinine (1.54±0.262 mg/dl), amylase (675±83 U/L) and lipase (12.2±1.04 U/L)], and these results were near or equal to organoprotective control [ALT (71.6±8.98I U/L), AST (121±28.1 U/L), ALP (916±103 U/L), urea (115±11.4mg/dl), creatinine (1.14±0.226 mg/dl), amylase (667±80 U/L) and lipase (16.6±2.02 U/L)]. The histopathological analysis also highlighted more organoprotection at this concentration as compared to other doses of extract.&#x0D; Conclusion: A. vera gel extract is an able organoprotective agent. This extract can be studied further for its active ingredients as a source of hepatoprotective and nephroprotective agents.

Zarawand Mudharaj (Aristolochia rotunda Linn.), an important medicinal plant used in Unani system of medicine: A review

Background: Zarawand Mudharaj (Aristolochia rotunda L.) belongs to family Aristolochiaceae. According to Unani scholars, it is a female plant of Aristolochia fontanesii Boiss. &amp; Reut. (Syn. A. longa L.), usually found growing in Mediterranean regions, Central Asia and South Europe.&#x0D; Purpose of the review: The main aim of this review is to highlight various aspects of Zarawand Mudharaj such as temperament, botanical description, pharmacological properties, therapeutic uses etc, as mentioned in Unani literature that will ultimately guide researchers to design various studies for further exploration of this important medicinal plant.&#x0D; Materials and methods: The present review has been carried out through extensive literature survey of various classical Unani and botanical texts, and published papers available on different search engines. The botanical names and their synonyms were validated through ‘The Plant List’ (www.theplantlist.org).&#x0D; Results: In Unani medicine, the rhizome of Zarawand Mudharaj is used for the treatment of several ailments viz. stomach and liver diseases, jaundice, cough, septic wounds, splenomegaly, gout etc. Apart from its use as single drug, it has also been added in many compound preparations viz. Anqarooya-i-Kabir, Habb-i-Rewand, Majun Falasifa, Majun Dabeedul Ward etc. A study on physicochemical standardization of rhizome of Aristolochia rotunda L. has reported the presence of moisture content, total ash, acid insoluble ash, water soluble ash, sulphated ash, alcohol and water-soluble extractive values within normal limits. The same study has also revealed that the hydro-alcoholic extract of rhizome of Aristolochia rotunda L. possesses significant hepatoprotective activity against CCl4 induced liver toxicity in albino Wistar rats. Several toxicity reports have pointed out that aristolochic acid containing herbal drugs including Aristolochia rotunda L. cause renal impairment and other serious adverse reactions. &#x0D; Conclusion: It is concluded that Aristolochia rotunda L. is widely used in Unani system of medicine. However, extensive studies on pharmacognosy, pharmacology, toxicology, phytochemistry and quality control of different parts of this potential medicinal plant have not been carried out so far. Therefore, such studies on modern scientific parameters may be conducted for further exploration so that the benefits may reach the masses.&#x0D; Keywords: Zarawand Mudharaj; Aristolochia rotunda L.; Unani medicine; Hepatoprotective; Aristolochic acid; Toxicity

Evaluation of the Antidote Activity of Nimbu swarasa (Citrus limon Linn.) on Jayapala Seed (Croton tiglium Linn.) Induced Toxicity in Wistar Albino Rats

Abstract: Background: Seeds of Jayapala (Croton tiglium Linn.) is a toxic compound which is commonly used in several Ayurvedic formulations following proper detoxification methods as mentioned in the Ayurvedic classics. Adarsha nigantu, one of the treatises of Ayurveda explains Nimbu swarasa (Lemon juice) as an antidote for Jayapala. The present study was aimed to determine the antidote activity of Nimbu swarasa (Citrus limon linn.) on Jayapala (Croton tiglium Linn.) seed induced toxicity on Wistar albino rats. Materials and Methods: A sub acute toxicity study was conducted on Wistar rats following the repeated dose 28 day oral toxicity study in rodents, 407 OECD guidelines which included administration of Jayapala seeds alone in one group and Jayapal seeds along with Nimbu swarasa in different doses in the other groups. Different haematological and biochemical parameters along with histopathology of important organs were carried out to access the antidote effect of Nimbu swarasa. Observation and Results: The repeated administration of Jayapala seed powder caused significant elevation in the serum liver enzymes like SGOT and SGPT (*P<0.5) and marked rise in the serum creatinine level. The co-administration of antidote Nimbu swarasa significantly attenuated Jayapala seed induced increase in the liver enzymes and reduced serum creatinine level. Histopathological examination of colon and jejunum revealed moderate epithelial cell erosions in Jayapala seeds administered group, whereas Nimbu swarasa caused mild to moderate protection in a dose dependant manner. Sections of spleen showed remarkable increase in the proportion of white pulp in toxicant group, whereas the Nimbu swarasa at higher dose level showed marked decrease in the white pulp proportion. The hepatic sections of toxicant group displayed mild cell infiltration and fatty changes in the hepatocyte with mild diffused necrosis whereas the sections of co-administration of antidotes showed normal cytoarchitecture. Conclusion: All the above findings are suggestive of Nimbu swarasa being an effective antidote against Jayapala induced toxicity. Key words: Antidote, Jayapala seeds, Nimbu swarasa, Haematological parameters, Histopathological examination, Toxicity.

The protective role of Diosmin, Hesperidine combination against heavy metals toxicity in Wistar albino rats: Biochemical, Immunohistochemical and Molecular Studies

The benchmark of this study is to evaluate the antioxidant protective efficiency of Diosmin-Hesperidin combination, a natural citrus flavone of hesperidin derivative on heavy metals intoxication and Oxidative stress-induced damage in Wistar albino rats. Oral doses of diosmin-hesperidin in rats (200 and 100 mg/kg body weight, respectively) for a month (every other day) prior to heavy metals intoxication. Evaluation of the protective and antioxidant effects of the combination of diosmin and hesperidin, various Rt-PCR estimations, biochemical estimations, histopathological alterations as well as comet assay and caspase-3 activity for assessment of apoptosis were performed. Results indicated that heavy metals intoxication-induced decline in the levels of liver tissue P53 gene expression and increase of liver tissues of the apoptotic caspase-3 gene, also induced decline in the levels of liver tissue antioxidant parameters (SOD, GPx, and GSH), increased lipid peroxidation (MDA), DNA damage and apoptosis, these parameters were improved by pre-administration of diosmin+hesperidine. Diosmin+hesperidine dose (200 and100 mg/kg body wt. respectively) restored the p53 and caspase-3 genes near-normal values, antioxidant status to near normal and reduced lipid peroxidation, DNA, and tissue damage. These results were confirmed by histopathological examinations, which showed that pre-administration of diosmin+hesperidine protected the liver of albino rats against heavy metals intoxication-induced damage. Hence, it has been illustrated that diosmin+hesperidine might be an effective antioxidant and protector against heavy metals intoxication-induced damage in rats. Moreover, the diosmin+hesperidine alone pretreated group did not show any biochemical alterations, fold change of P53 or caspase-3 genes or DNA damage indicating the protective nature of the drug.

Composition of the Essential Oil Thymus schimperi and Evaluation of Its Acute and Subacute Toxicity in Wistar Albino Rats: In Silico Toxicity Studies.

Background In Ethiopian traditional medicine, the aerial part of Thymus schimperi is widely used to treat diseases such as gonorrhea, cough, liver disease, kidney disease, hypertension, stomach pain, and fungal skin infections. However, there is insufficient investigation on the toxic effect of the essential oil of T. schimperi. The aim of this study was, therefore, to evaluate the acute, subacute, and in silico toxicity of Thymus schimperi essential oil in the Wistar albino rats. Method Essential oil of the aerial part of T. schimperi extracted by hydrodistillation was analyzed by GC-MS. The oil was subjected to toxicity studies. In the acute toxicity study, rats were randomly divided into seven groups (n = 5). The control group received only distilled water with 2% of tween 80, whereas the experimental groups received single doses of 300, 600, 900, 1200, 1500, and 2 000 mg/kg of the oil. In the subacute toxicity study, rats were randomly divided into four groups (n = 10). The control group received distilled water with 2% of tween 80, whereas the experimental groups received 65 mg/kg, 130 mg/kg, and 260 mg/kg of the oil orally for 28 days. At the end of the experiment, blood samples were collected for hematology and clinical chemistry evaluation. Gross pathology and histopathology of the liver and the kidneys were also evaluated. For the in silico toxicity study, PubChem CID numbers of GC-MS identified bioactive compounds in the essential oil of T. schimperi obtained from PubChem. Chemdraw (8.0) was used to construct two-dimensional structures of the compounds. The Swiss ADMET web tool was used to convert the two-dimensional structures into a simplified molecular-input line input system (SMILES). In addition, the toxicity parameters were predicted via vNN and ADMET servers. Results In this study, the LD50 of the essential oil of T. schimperi was found to be 1284.2 mg/kg. According to the World Health Organization, the oil is classified as moderately hazardous in its oral administration. In the subacute toxicity study, rats showed no significant changes in behavioral indices, gross pathology, body weight, biochemical, and most hematological parameters. However, hematological profiles showed a significant decrement in WBC counts and a significant increment of MCV in high dose (260 mg/kg) groups as compared to the control group. Furthermore, no significant differences were observed between the control and essential oil-treated groups, observed in the gross histopathology of the liver and the kidneys. In the in silico toxicity study, all compounds derived from the essential oil showed no cardiac toxicity (h-ERG Blocker), AMES (Ames Mutagenicity), and cytotoxicity via ADMET and vNN-ADMET toxicity predictors. However, by using these servers, about 8.6% of the compounds showed hepatotoxicity, only 3.45% caused drug-induced liver injury, and only 1.75% were potentially toxic to the mitochondrial membrane. Conclusion From the results of this study, oral administration of the essential oil T. schimperi up to a dose of 130 mg/kg is not harmful. However, in the high-dose (260 mg/kg) group, the WBC count was significantly decreased and the MCV was significantly increased. In the in silico toxicity study, most of the components of the oil were found to be nontoxic, although a few of the compounds showed hepatotoxicity and mitochondrial membrane potential toxicity. It is, therefore, essential to conduct chronic toxicity of the essential oil as well as its components, which showed toxicity in the in silico study before using preparations containing the essential oil of T. schimperi.

Blood glucose lowering effect of Solanum melongena (garden egg), Solanum lycopersicum (tomatoes), Daucus carota subsp. Sativus (carrot) extracts on lead induced toxicity in albino wistar rats

Lead is one of the heavy metal humans are often expose to either through food, cosmetics or environment. This study is aimed at investigating the positive effect of Solanum melongena (garden egg), Solanum lycopersicum (tomatoes) and Daucus carrots subsp.sativus (carrot) on blood glucose concentration, body weight, and feeding habits of albino rats on lead toxicity. In this study 35 albino rats weighing 80-120g were grouped into five. Group 1 served as normal control, group 2 negative control. The remaining three groups served as treatment groups 1, 2 and 3. All groups except group 1 (normal control) were administered 50mg/kg of lead acetate. Treatment groups were administered 200mg/kg of Solanum melongena (garden egg), Solanum lycopersicum (tomatoes) and Daucus carrots subsp.sativus (carrot). Group 3 was administered Solanum malongen and Daucus carrots subsp.sativus while group 4 was given Daucus carrots subsp.sativus and solanum lycopersicon. Group 5 was administered Solanum malongen, Daucus carrots subsp.sativus and Solanum lycopersicon. Changes in blood glucose concentration, body weight, feed and water consumption recorded at intervals. The result showed a significant decrease (P&lt;0.05 and P&lt;0.01) in blood glucose concentration in treatment groups compared to negative control. There was also significant increase (P&gt;0.05, P&gt;0.01 and P&gt;0.001) in body weight and feed consumed in treatment groups compared to negative control. Combined therapy of any two of Solanum malongen, Daucus carrots subsp.sativus and Solanum lycopersicon juice can help in the management of hyperglycemia and reverse internal abnormality or injury resulting in weight loss in lead induced toxicity.

Blood glucose lowering effect of Solanum melongena (garden egg), Solanum lycopersicum (tomatoes), Daucus carota subsp. Sativus (carrot) extracts on lead induced toxicity in albino wistar rats

Blood glucose lowering effect of Solanum melongena (garden egg), Solanum lycopersicum (tomatoes), Daucus carota subsp. Sativus (carrot) extracts on lead induced toxicity in albino wistar rats

Protective effect of Solanum melongena (garden egg), Solanum lycopersicum (tomatoes), Daucus carota subsp. sativus (carrot) extracts on some electrolytes and renal biomarkers of lead induced toxicity in albino wistar rats

Protective effect of Solanum melongena (garden egg), Solanum lycopersicum (tomatoes), Daucus carota subsp. sativus (carrot) extracts on some electrolytes and renal biomarkers of lead induced toxicity in albino wistar rats