scholarly journals Toxicological Assessment of Venlafaxine: Acute and Subchronic Toxicity Study in Rats

2018 ◽  
Vol 37 (4) ◽  
pp. 327-334 ◽  
Author(s):  
Melad G. Paulis ◽  
Essam M. Hafez ◽  
Nashwa F. El-Tahawy ◽  
Mohmed K. M. Aly
Keyword(s):  
Psychiatric Treatment ◽  
Histopathological Examination ◽  
Clinical Manifestations ◽  
Kidney Injury ◽  
Toxic Effects ◽  
High Dose ◽  
Toxicological Assessment ◽  
Liver And Kidney ◽  
Glutamyl Transferase ◽  
Therapeutic Doses

Antidepressants are the most commonly prescribed drugs for psychiatric treatment, and venlafaxine (VEN) is one of the most popular options. Venlafaxine is a nontricyclic dual-acting serotonin–norepinephrine reuptake inhibitor. Although an increased incidence of acute toxicity and addiction has been reported, controlled studies examining its toxic effects on different organs are still lacking. This study investigated the possible toxic effects of VEN on the liver, kidney, and gastric tissues. Three groups of rats were administered saline, a single LD50 dose (350 mg/kg), or 100 mg/kg VEN daily, followed by increases in the dose of 50 mg/kg every 10 days for 30 days (about 10 times the therapeutic doses). The following parameters of liver and kidney injury were then assayed: alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, prothrombin time, partial thromboplastin time, blood urea nitrogen, and serum creatinine. A histopathological examination was then conducted. Both acute and subchronic administration of VEN produced multiple clinical manifestations in the experimental animals, including seizures, coma, and even death. Moreover, the liver and renal function tests indicated injury in these tissues. Furthermore, the histopathological examination showed signs of organ toxicity after both acute and chronic VEN exposure. This study has shown that VEN has harmful effects on the liver, kidney, and stomach in either a single high dose (LD50) or repeated exposure to 10 times the therapeutic doses. As a result, strategies to increase awareness of these effects among physicians and the public are needed because this drug may be addictive.

scholarly journals Toxicological Investigations of Aristolochia longa Root Extracts

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Nasreddine El Omari ◽  
Omar El Blidi ◽  
Abdelhakim Bouyahya ◽  
Karima Sayah ◽  
Saad Bakrim ◽  
...  
Keyword(s):  
Histopathological Examination ◽  
Global Analysis ◽  
Clinical Signs ◽  
Experimental Period ◽  
High Dose ◽  
Herbaceous Plant ◽  
Oral Toxicity ◽  
Toxicity Potential ◽  
Liver And Kidney

Aristolochia longa L. (Aristolochiaceae) is an herbaceous plant recognized in alternative medicine for its many therapeutic virtues. The aim of this study was to determine the pharmacotoxicological effects of this plant in order to ensure safe clinical use. The oral toxicity of the aqueous extract of A. longa roots was performed in vivo on Wistar rats at doses of 0.8, 1.25, 2, 2.5, and 5 g/kg/day for 21 days. Clinical signs were observed throughout the experimental period, followed by measurement of body weight change, while selected biochemical parameters, as well as relative organ weights and the histology of liver, kidney, and intestinal tissues, were evaluated after 6, 11, and 16 days and then at the end of 21 days of daily administration. At repeated doses for 21 days, the extract contributed to significant weight gain, in both control and treated rats. The global analysis of hepatic and renal biomarkers showed a significant increase between control and different doses of the extract, from the first to the third week of treatment, indicating the likely toxic effect of the extract on liver and kidney function. Organ toxicity was confirmed by histopathological examination, which revealed greater renal and hepatic parenchymal changes in animals treated with a high dose beyond the 16th day. At the end of the treatment, relatively small size of intestinal villi was also observed. It was concluded that ALAE has a low toxicity potential in nonprolonged oral administrations. However, at high chronic oral doses, A. longa appears to have significant toxicity on the organs tested.

scholarly journals Protective Effect of Ethanolic Extract of Grape Pomace against the Adverse Effects of Cypermethrin on Weanling Female Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Abdel-Tawab H. Mossa ◽  
Faten M. Ibrahim ◽  
Samia M. M. Mohafrash ◽  
Doha H. Abou Baker ◽  
Souad El Gengaihi
Keyword(s):  
Body Weight ◽  
Protective Effect ◽  
Ethanolic Extract ◽  
Serum Marker ◽  
Grape Pomace ◽  
Female Rats ◽  
High Dose ◽  
Gamma Glutamyl Transferase ◽  
Liver And Kidney ◽  
Glutamyl Transferase

The adverse effect of cypermethrin on the liver and kidney of weanling female rats and the protective effect of ethanolic extract of grape pomace were investigated in the present study. Weanling female rats were given cypermethrin oral at a dose of 25 mg kg−1body weight for 28 consecutive days. An additional two Cyp-trated groups received extract at a dose of 100 and 200 mg kg−1body weight, respectively, throughout the experimental duration. Three groups more served as extract and control groups. Administration of Cyp resulted in a significant increase in serum marker enzymes, for example, aminotransferases (AST and ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT), and increases the level of urea nitrogen and creatinine. In contrast, Cyp caused significant decrease in levels of total protein and albumin and caused histopathological alterations in liver and kidneys of female rats. Coadministration of the extract to Cyp-treated female rats restored most of these biochemical parameters to within normal levels especially at high dose of extract. However, extract administration to Cyp-treated rats resulted in overall improvement in liver and kidney damage. This study demonstrated the adverse biohistological effects of Cyp on the liver and kidney of weanling female rats. The grape pomace extract administration prevented the toxic effect of Cyp on the above serum parameters. The present study concludes that grape pomace extract has significant antioxidant and hepatorenal protective activity.

scholarly journals Synergistic renoprotective effects of sesame oil and erythropoietin on ischemic kidney injury after renal transplantation

AMB Express ◽  
2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Liyu Ye ◽  
Fang Xiao ◽  
Jijun Xie ◽  
Lingling Feng ◽  
Zhangjun Tang ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Kidney Transplantation ◽  
Reduced Glutathione ◽  
Histopathological Examination ◽  
Fetal Liver ◽  
Combined Treatment ◽  
Kidney Injury ◽  
Positive Control ◽  
Sesame Oil ◽  
Liver And Kidney

AbstractIn this study, we evaluated the combined therapeutic efficacy of erythropoietin (a hematopoietic hormone produced by the fetal liver and kidney in response to inflammation and apoptosis) and sesame oil (from Sesamum indicum L.) on ischemic kidney injury following kidney transplantation in a rat model. Rats were assigned to the following groups: sham, control, 1000 U/kg erythropoietin, 1 mL/kg sesame oil, 1000 U/kg erythropoietin + 1 mL/kg sesame oil, and positive control. We measured the levels of blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), lipid peroxidation, reactive oxygen species (ROS), reduced glutathione (GSH), antioxidant enzymes, and proinflammatory markers and performed renal histopathological evaluation. The combined erythropoietin and sesame oil treatment significantly reduced BUN, ALT, creatinine, lipid peroxidation, ROS, and proinflammatory markers and GSH and antioxidant enzyme levels. Histopathological examination showed that the combined erythropoietin and sesame oil treatment significantly reduced necrosis. Therefore, combined treatment of sesame oil and erythropoietin may represent an effective therapeutic approach against ischemic kidney injury after kidney transplantation.

scholarly journals Nephrotoxicity Assessment of Dr Iguedo Goko Cleanser® in Exposed Wistar Rats

2020 ◽  
pp. 30-40
Author(s):  
Godswill J. Udom ◽  
Jude E. Okokon ◽  
John A. Udobang ◽  
Daniel N. Obot ◽  
Ikanna E. Asuquo
Keyword(s):  
Acute Toxicity ◽  
Wistar Rats ◽  
Histopathological Examination ◽  
Male Rats ◽  
Herbal Remedies ◽  
High Dose ◽  
Cortical Tissue ◽  
Toxicological Assessment ◽  
Tissue Cells ◽  
Convoluted Tubules

Aims: This study was designed to evaluate the toxicity concern of Dr Iguedo Goko Cleanser® on kidney function parameters and histoarchitecture of the kidneys of exposed Wistar rats. Study Design: A 60-day subchronic toxicological assessment using animal model. Place and Duration of Study: Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Uyo, Nigeria, between March 2019 and July 2019. Methodology: Acute toxicity study was conducted using the modified Lorke’s method. Thirty Wistar rats of both genders were randomly allotted to six groups (5/group) and orally-treated daily thus: Groups 1 and 4-Controls (distilled water, 10 mL/kg), Groups 2-3; 5-6 received the Polyherbal mixture (476.24; 158.75) mg/kg, respectively. On 62nd day, animals were euthanized under diethyl ether anaesthesia and sacrificed. Blood samples were collected by cardiac puncture for biochemical analysis. Eviscerated kidneys were weighed and fixed in 10% formalin for histopathological examination. Results: Polyherbal mixture presented acute toxicity with an estimated LD50 of 1587.45 mg/kg (mouse, i.p). Results presented significant (P=.05) decreased blood urea nitrogen at all doses tested; elevated Na+ for high dose male (124.58±1.82) and female (122.77±0.00) rats compared to their respective controls (110.49±3.17/97.33±1.78) as well as increased creatinine levels for low dose male rats (145.83±7.45) compared to control (36.46±1.24). Histopathology of the kidneys revealed degrees of pathologies such as hyperplasic glomerular cells, occluding Bowman’s space, hyperaemia within the cortical tissue, widened proximal and distal convoluted tubules, hyperplasia of cortical tissue cells as well as hyperplasia of tubular and connective tissue cells. Conclusion: Despite the popular claim that herbal remedies are completely natural, safe and devoid of toxicities whatsoever, the present day study suggest otherwise. Therefore, utmost caution and/or avoidance of the polyherbal mixture whenever possible, is strongly advised especially as its nephrotoxic potentials are not negligible.

scholarly journals Ameliorating Effect of Moringa against Liver and Kidney Injury Induced by Monosodium Glutamate

2019 ◽  
pp. 1-10
Author(s):  
Rehab M. El-Gharabawy ◽  
Amira S. Ahmed ◽  
Thara I. Al-Adhadh
Keyword(s):  
Liver Injury ◽  
Histopathological Examination ◽  
Monosodium Glutamate ◽  
Kidney Injury ◽  
Normal Structure ◽  
Male Rats ◽  
Control Group ◽  
Renal Tubules ◽  
Total Proteins ◽  
Liver And Kidney

Background: Monosodium glutamate (MSG) produces adverse and damaging effects in different organs like liver and kidneys. Moringa has ameliorating effect on kidney and liver injury induced by monosodium glutamate. Objective: To study the ameliorating effect of moringa against rats liver and kidney injury induced by monosodium glutamate. Design: Prospective study. Setting: College of Pharmacy, Qassim University. Materials and Methods: This study was performed on 20 male rats and equally divided into 4 groups. The first group was control group, second group was moringa group, third group was MSG group and forth group was MSG plus moringa group. We determined liver function, albumin, total protein, kidney function, electrolytes and histopathological examination of tissue. Main Outcome Results: Moringa has ameliorating effect on kidney and liver injury induced by monosodium glutamate. Sample Size:  A total of 20 malerats. Results: There was a significant increase in the levels of serum aspartate transaminase (AST) and alanine transaminase (ALT), alkaline phosphatase (ALP), urea and creatinine. Significant decrease in the levels of albumin, total proteins and sodium levels in rats treated with monosodium glutamate. Kidney sections revealed normal structure of glomeruli and renal tubules as control group, liver revealed good improvements and mild cellular infiltrations were observed in rats treated with MSG and moringa group. Conclusion: Moringa causes ameliorating effect on kidney and liver injury induced by monosodium glutamate in rats. Limitation of the Study: Few studies about the protective effect of Moringa against toxic effect of MSG.  So we need to focus on its beneficial effect against toxicity induced by MSG.

Rare Ginsenoside 20(R)-Rg3 Inhibits D-Galactose-Induced Liver and Kidney Injury by Regulating Oxidative Stress-Induced Apoptosis

2020 ◽  
Vol 48 (05) ◽  
pp. 1141-1157 ◽  
Author(s):  
Wei Li ◽  
Jian-Qiang Wang ◽  
Yan-Dan Zhou ◽  
Jin-Gang Hou ◽  
Ying Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Kidney Injury ◽  
Treated Group ◽  
High Dose ◽  
Lipid Peroxidation Product ◽  
Stress Injury ◽  
Beneficial Effects ◽  
Liver And Kidney ◽  
Induced Apoptosis

Oxidative stress is considered as a major factor in aging and exacerbates aging process through a variety of molecular mechanisms. D-galactose, a normal reducing sugar with high dose can cause the accumulation of reactive oxygen species (ROS) or stimulate free radical production indirectly by the formation of advanced glycation end products in tissues, finally resulting in oxidative stress. 20(R)-ginsenoside Rg3 (20(R)-Rg3), a major and representative component isolated from red ginseng (Panax ginseng C.A Meyer), has been shown to observably have an anti-oxidative effect. We thereby investigated the beneficial effects of 20(R)-Rg3 on D-galactose-induced oxidative stress injury and its underlying mechanisms. Our results showed that continuous injection of D-galactose with 800[Formula: see text]mg/kg/day for 8 weeks increased the levels of alanine aminotransferase (ALT) and blood urea nitrogen (BUN). However, such increases were attenuated by the treatment of 20(R)-Rg3 for 4 weeks. Meanwhile, 20(R)-Rg3 markedly inhibited D-galactose-caused oxidative stress in liver and kidney. The anti-oxidants, including catalase (CAT) and superoxide dismutase (SOD), were elevated in the mice from 20(R)-Rg3-treated group compared with that from D-galactose group. In contrast, a significant decrease in levels of cytochrome P450 E1 (CYP2E1) and the lipid peroxidation product malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) were observed in the 20(R)-Rg3-treated group. These effects were associated with a significant increase of AGEs. More importantly, 20(R)-Rg3 effectively attenuated D-galactose induced apoptosis in liver and kidney via restoring the upstream PI3K/AKT signaling pathway. Taken together, our study suggests that 20(R)-Rg3 may be a novel and promising anti-oxidative therapeutic agent to prevent aging-related injuries in liver and kidney.

Effect of Ocimum basilicum leaves extract on acetaminophen-induced nephrotoxicity in BALB/c mice

2018 ◽  
Vol 16 (2) ◽  
Author(s):  
Hajar F. Karaali ◽  
Ragaee R. Fahmi ◽  
Jamilah M. Borjac
Keyword(s):  
Renal Toxicity ◽  
Histopathological Examination ◽  
Kidney Injury ◽  
Serum Markers ◽  
Ocimum Basilicum ◽  
Induction Treatment ◽  
Histopathological Analysis ◽  
Additional Increase ◽  
Liver Functions ◽  
Liver And Kidney

Abstract Background Acetaminophen (APAP) is one of the most widely used drugs to treat pain. Its overdose is lethal causing liver and kidney failure. Nephrotoxicity and hepatotoxicity are mostly due to the overproduction of reactive oxygen species. Ocimum basilicum, known as basil, is a commonly used medicinal plant due to its versatile role as antibacterial, antifungal, and anti-oxidative. We aim in this study to investigate the preventive and protective effect of basil leaves aqueous extract against APAP-induced hepatorenal toxicity in BALB/c mice. Methods Acute kidney injury (AKI) was induced in mice using APAP. Mice were treated with basils extract pre and post AKI induction. Kidney and liver functions were assessed by measuring creatinine, urea, alanine transaminase, and aspartate transaminase levels in serum. Superoxide dismutase, catalase (CAT), and malondialdehyde levels of renal and hepatic tissues were assayed using Elisa. Kidney injury molecule (KIM-1) was quantified in kidney homogenate. Histopathological analysis of kidney and liver were examined. Results Significant increase in all serum parameters, in hepatic and renal MDA, and in renal KIM-1 levels was observed post AKI induction. Treatment with basils post AKI induction minimized APAP damage by reducing serum markers and MDA in both organs and by increasing SOD and CAT. However, pretreatment with basils extract caused additional increase in serum ALT and AST and MDA in liver, with a significant increase in renal antioxidant enzymes. These results were confirmed by histopathological examination. Conclusion Basil extract may act as a natural antioxidant to treat APAP-induced acute hepato-renal toxicity when used as a post-treatment.

Histopathological changes in the Kidney and Liver of Albino Rats treated with Extract of Acalypha Wilkesiana

2019 ◽  
Vol 2 (1) ◽  
pp. 19-41
Author(s):  
C.E. Okorochi ◽  
G.O. Oze ◽  
A.C. Okorochi ◽  
A.U. Obi ◽  
R.N. Oze ◽  
...  
Keyword(s):  
Body Weight ◽  
Histopathological Examination ◽  
Significant Loss ◽  
The Body ◽  
Albino Rats ◽  
High Dose ◽  
Histopathological Changes ◽  
Key Words Nephrotoxicity ◽  
Liver And Kidney ◽  
Acalypha Wilkesiana

Aim: The hepatotoxic and nephrotoxic effects of Acalypha wilkesiana extract on rat liver and kidney were studied on 40 male Wister albino rats weighing 180 – 200g. Methodology: The animals were divided into 5 groups of eight rats each. They were administered 0mg/kg, 480mg/kg, 960mg/kg, 1440mg/kg and 1920mg/kg body weight of Acalypha wilkesiana extract orally. After seven days, four animals from each group were sacrificed under ether anaesthesia. At the end of another seven days, the rest of the animals were sacrificed. The liver and kidney were harvested for hispathological examination using H & E staining procedures. The body weight of the animals, the weight of the liver and kidney were also taken. Results: The results showed a significant loss in body weight (p<0.05) of the animals treated with 1440mg.kg and 1920mg/kg of the extract for 14 days (2.41 + 0.03 and 2.8 + 0.02) compare with the control (3.7 + 0.02). There were no apparent differences in the relative weights of the liver and kidney in the treated and control groups. The histopathological examination result showed that rats in the low dose (480mg/kg body weight) group showed normal histo-architecture with the control in 7 and 14 days of exposure to the extract, while those in the high dose (960mg/kg, 1440mg/kg and 1920mg/kg) groups showed histopathological changes after 14 days, which ranged from moderate to severe tubular necrosis, glomerular inflammation, to interstitial nephritis. The result suggests a likely alteration in hepatic and renal function and possible hepato and nephrotoxicity respectively. These were dose and duration dependent. Conclusion: The outcome suggests that the plant extract maybe injurious to man on prolonged usage and higher doses. The need for the health education of the users may be necessary. Key Words: Nephrotoxicity, Hepatotoxicity, Acalypha wilkesiana extract, rats.

scholarly journals New Insights in the Pathogenesis of Cisplatin-Induced Nephrotoxicity

2019 ◽  
Vol 0 (0) ◽  
Author(s):  
Bojana Djokovic ◽  
Marina Gazdic Jankovic ◽  
C. Randall Harrell ◽  
Crissy Fellabaum ◽  
Nebojsa Arsenijevic ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Clinical Manifestations ◽  
Kidney Injury ◽  
High Dose ◽  
Salt Wasting ◽  
New Therapeutic Approaches ◽  
Forced Diuresis ◽  
Proximal Tubular Epithelial Cells ◽  
Urinary Concentrating Ability

Abstract Cisplatin (cis-diamminedichloroplatinum II) is a widely used chemotherapeutic agent. However, efficacy and clinical utility of this drug is significantly limited by severe side effects such as nephrotoxicity which develops due to renal accumulation and bio-transformation in proximal tubular epithelial cells. Cisplatin-induced nephrotoxicity can be manifested as acute kidney injury (AKI), or as different types of tubulopathies, salt wasting, loss of urinary concentrating ability, and magnesium wasting. The attenuation of cisplatin-caused AKI is currently accomplished by hydration, magnesium supplementation or mannitol-induced forced diuresis. However, mannitol treatment causes over-diuresis and consequent dehydration, indicating an urgent need for the clinical use of newly designed, safe and efficacious renoprotective drug, as an additive therapy for high dose cisplatin-treated patients. Accordingly, we emphasized current knowledge regarding molecular mechanisms responsible for cisplatin-caused nephrotoxicity and we described in detail the main clinical manifestations of cisplatin-induced renal dysfunction in order to pave the way for the design of new therapeutic approaches that can minimize detrimental effects of cisplatin in the kidneys. Having in mind that most of cisplatin-induced cytotoxic effects against renal cells are, at the same time, involved in anti-tumor activity of cisplatin, new nephroprotective therapeutic strategies have to prevent renal injury and inflammation without affecting cisplatin-induced toxicity against malignant cells.

Acetaminophen: Neonatal hepatotoxicity due to late pregnancy exposure

1987 ◽  
Vol 45 ◽  
pp. 718-719
Author(s):  
G.A. Miranda ◽  
M.A. Arroyo ◽  
C.A. Lucio ◽  
M. Mongeotti ◽  
S.S. Poolsawat
Keyword(s):  
Low Dose ◽  
Fetal Liver ◽  
Late Pregnancy ◽  
Toxic Chemicals ◽  
Control Group ◽  
High Dose ◽  
Over The Counter ◽  
Liver And Kidney ◽  
Neonatal Liver ◽  
Childbearing Women

Exposure to drugs and toxic chemicals, during late pregnancy, is a common occurrence in childbearing women. Some studies have reported that more than 90% of pregnant women use at least 1 prescription; of this, 60% used more than one. Another study indicated that 80% of the consumed drugs were not prescribed, and of this figure, 95% were “over-the-counter” drugs. Acetaminophen, the safest of all over-the-counter drugs, has been reported to induce fetal liver necrosis in man and animals and to have abortifacient and embryocidal action in mice. This study examines the degree to which acetaminophen affects the neonatal liver and kidney, when a fatty diet is simultaneously fed to the mother during late pregnancy.Timed Swiss Webster female mice were gavaged during late pregnancy (days 16-19) with fat suspended acetaminophen at a high dose, HD = 84.50 mg/kg, and a low dose, LD = 42.25 mg/kg; a control group received fat alone.

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