Pazopanib-Induced Hepatotoxicity in an Experimental Rat Model

Chemotherapy ◽  
2018 ◽  
Vol 63 (1) ◽  
pp. 39-45
Author(s):  
Bulent Cetin ◽  
Guldal Esendagli Yılmaz ◽  
Berkan Armagan ◽  
Baris Afsar ◽  
Umut Demirci ◽  
...  

Pazopanib is an effective treatment for advanced renal cell carcinoma and soft tissue sarcoma. Besides classical adverse events of this drug class, hepatotoxicity has been described as a frequent side effect. The aim of the present study was to evaluate the effect of pazopanib on the liver in an experimental rat model. Sixteen Wistar albino rats were divided into 3 groups: experimental toxicity was induced with pazopanib (10 mg/kg) administered for 28 days (group 2) or 56 days (group 3) orally by gavage. Group 1 (control group) received only distilled water. Rats in groups 2 and 3 were sacrificed after the collection of blood and tissue samples on the 28th and 56th days, respectively. We found significant differences in bilirubin, alkaline phosphatase, lactate dehydrogenase, glucose, triglyceride, very-low-density lipoprotein, and iron values (p < 0.050 for all) but none in any other parameter (p > 0.050). All rats in the control group had normal histological features; however, none of the rats in groups 2 and 3 showed normal histology. In group 2, we observed mild sinusoidal dilatation, congestion, enlarged Kupffer cells, accumulation of yellow-brown-black pigment in the Kupffer cells and the accumulation of hemosiderin with Prussian blue reaction in the hepatocytes. In group 3, the findings mentioned above were more prominent, and besides these findings focal acinar transformation and macrovesicular steatosis were also observed. In group 3, mild inflammation within the portal areas was observed consisting of lymphocytes, neutrophils, and eosinophils. This study is the first that reports the biochemical and histopathological evaluation of pazopanib-related hepatic toxicity.

Author(s):  
Aminu Lailaba Abubakar ◽  
Jabir Aliyu Danyaya ◽  
Kabiru Abubakar ◽  
Magaji Umar Faruk ◽  
Yusuf Saidu

Peripartum cardiomyopathy (PPCM) is a rare but devastating cardiac failure of indeterminate etiology occurring in late pregnancy or early puerperium. The prevalence of PPCM in Northern Nigeria could be attributed to the unique customary puerperal practices of prolonged consumption oflarge quantities of Guiera senegalensis and Natron. This study investigated the effect of decoction of G. senegalensis with and without Natron on cardiac markers, lipid profile and histology ofheart in postpartum female albino rats using standard methods.Thirty-five (35)female albino rats of body weights 190-200 g of five month were randomly grouped into seven (7) of five rats each. Group 2, 3 and 4 were orally administered with 100, 200 and 300 mg/kg body weight of G. senegalensis. Group 5, 6 and 7 were orally administered with 100, 200 and 300 mg/kg body weight (1:1) of G. senegalensis and Natron by gavage, whereas group 1 received distilled water. The study revealed significant (p< 0.05) decrease in triglyceride(TG) in group 2 to VII, high density lipoproteincholesterol (HDL-c) in group 2, 5 and 6, very low density lipoprotein- cholesterol (VLDL-c) in group 3 to V, couples with significant (p< 0.05) increase in low density lipoprotein cholesterol (LDL-c) in group 2, 3, 5 and 7, and for (AIX) in group 2, total cholesterol(TC) in group 2, 3 and 7 when compared with control. Significant (p< 0.05) increase in Lactate dehydrogenase (LDH) in group 3 to 7, and Myoglobin (MB) in group 3 was observed. Significant (p< 0.05) decrease in Troponin I (TnI) in group 2 and 4 was seen. There were no significant (p>0.05) changes in Troponin T (Tn T), aspartate amino transferase (AST) and Creatine Kinase(CK-NAC) of the treatment group when compared to control group. Histopathological examination of section of the heart revealed ventricular dilatation, hypertrophied with enlarged nuclei, stretched, and irregular and mural thrombi in group 2 to 4 and 7. Inflammation in group 5 and 7, Pigment deposited in group 4 to 7 and Mild fibrosis in group 3 were observed. The study demonstrates that consumption of G. senegalensis and Natron for 28 days’induces dyslipidemia and causes changes in the heart of postpartum rats and thus may contribute to the pathogenesis of PPCM.


Author(s):  
M. O. Enemali ◽  
J. Akolo ◽  
G. S. Haruna ◽  
J. E. Bulus ◽  
P. J. Kassah ◽  
...  

Leaves of I. batatas have been implicated in both the hematopoietic process and in the management of hyperlipidemia in man. The current study evaluated the hematopoietic potentials and the lipid profile stabilizing potential of ethanol leaf extract of I. batatas in albino rats. The study was carried out at the Department of Biochemistry and Molecular Biology of the Nasarawa State University, Keffi, between March 2019 and October 2019. The determination of the phytochemical composition of the leaves was carried out. Sixteen albino rats weighing between 100-150g were randomly distributed into 4 groups of 4 rats each. Animals in group 1 served as the control while animals in groups 2, 3, and 4 served as the test groups and were administered 200, 300 and 400g/kg body weight respectively of ethanol leaf extract of I batata for fourteen days following standard procedures. The extract contained terpenoids in high amount, flavonoids and alkaloids in moderate amounts, while glycosides, phenolic, and steroids were present in low amounts. WBC counts increased significantly across the test groups compared to the control. PLT decreased significantly (P = 0.05) in all the test groups when compared to the control group. MCV increased significantly (P = 0.05) in all the test groups when compared to the control group. MCH increased significantly (P = 0.05) in group 2 but decreased significantly in groups 3 and 4 when compared to the control group. The lipid profile parameters; triglycerides (TAG), total cholesterol (TC), low density lipoprotein (LDL-C) showed no significant changes but HDL-C decreased significantly in group 4 compared to the control. The outcome of this study revealed that the ethanol leaves extract of I. batatas may possess a hematopoietic effect but may not be effective in the management of hyperlipidemia.


2020 ◽  
Vol 73 (4) ◽  
pp. 746-750
Author(s):  
Oksana S. Khukhlina ◽  
Oksana D. Liakhovych ◽  
Ludmila V. Kaniovska ◽  
Olena V. Kaushanska ◽  
Alona A. Antoniv ◽  
...  

The aim: To estimate the diagnostic and predictive value of anthropometric indices indicating obesity and glycemic parameters in the progression of NASH due to comorbidity with OA and OB. Materials and methods: 90 patients were examined and distributed into three groups: group 1 included patients suffering from OA, grade II-III according to Kellgren and Lawrense classification, with normal body mass, group 2 -patients with NASH and obesity without OA, group 3 -patients with OA, NASH and obesity. The control group consisted of 30 healthy individuals of the corresponding age. Results: There was a correlation between lipid and carbohydrate metabolism. This fact was confirmed by the evidence that under the influence of IR there was an increase in the level of lipoproteins enriched in triglycerides, the concentration of cholesterol of low density lipoprotein and reduction in level cholesterol of high density lipoprotein, which led to the progression of the clinical course of NASH. It was established that anthropometric indices of patients with comorbid flow of NASH, OA and OB were significantly (p <0.05) higher than in experimental groups. A positive correlation was found between some anthropometric indices and the following glycemic parameters: fasting blood glucose, HOMA-IR suggested that insulin resistance contributed to the growth of glycated compounds leading not only to the progression of NASH and affect the dysfunction of chondrocytes, but also influencing destruction of subchondral bone in osteoarthritis. Conclusions: The outcomes of the study result in the necessity of studying the metabolic status in patients with a comorbid progression of NASH, OB and OA for timely correction of the revealed disorders, which will reduce the run of NAFLD.


2021 ◽  
pp. 75-76
Author(s):  
Bharat Bhushan ◽  
Debarshi Jana

Background: Dyslipidemia is very much common in chronic kidney disease patients and is responsible for cardiovascular disease (CKD) which is most common cause of mortality in them. So, it is necessary to study the lipid prole in CKD patients to prevent morbidity and mortality. Methods: Subjects each of 50 in number are grouped into healthy controls (group-1), CKD patients without hemodialysis (group-2), CKD patients with hemodialysis (group-3). After fasting of 12 hours, lipid prole is assessed in all cases. Results: In this study, there is increase in Total cholesterol (TC), Low Density lipoprotein (LDL), very Low-Density lipoprotein (VLDL) and Triglycerides (TG) and decrease in High Density Lipoprotein (HDL) in all CKD patients compared to healthy controls (p-value for each parameter <0.001). There is increase in TC, TG and VLDL in diabetic CKD patients compare to non-diabetic CKD patients and p-value for each parameter is <0.05. It was found that TG and VLDL increase and HDL decrease in group-3 compare to group-2 is statistically signicant (p-value for each <0.05) and no signicant variation in TC and LDL in these groups. Conclusions: Present study demonstrated that there is dyslipidemia in CKD patients irrespective of mode of management, but the derangement is much more common and signicant in CKD with hemodialysis group and they are at risk of cardiovascular disease. It is better to start lipid lowering drugs which decreases disease progression and dyslipidemia.


2021 ◽  
Author(s):  
Wael Abdou Hassan ◽  
Shaimaa Shehata ◽  
Ahmad ElBana

Abstract Background: Pregabalin (PGB) used as analgesic in treatment of neurogenic pains of chronic diseases, is considered as one of the most abused anti-epileptic drugs worldwide and it has been proved that it induces addictive behaviors. The present histopathological study aimed to identify the effect of PGB administration on cerebral cortex and cerebellar cortex, in both acute and chronic toxicity. Seventy-two male and non-pregnant female adult albino rats’ 6- to 8-week-old divided into 3 main groups of 24 rats each were studied. Group 1 represented the control group and group 2 represented the acute toxicity group, in which rats were given a single dose of PGB (5000 mg/kg) orally by gavage and after 24 hours, rats were sacrificed and examined. Group 3 represented the chronic toxicity group; were given PGB 500 mg/kg orally by gavage for 12 weeks, after which rats were sacrificed and examined. Result: Cerebral cortex tissue of acute toxicity group displayed astrocytosis and dystrophic changes, while in chronic group showed degeneration, necrosis and cellular infiltrates. The cerebellum of chronic groups showed degeneration and shrunken of Purkinje cells. Conclusion: Acute and chronic intoxication with pregabalin adversely altered the structure of cerebral cortex and cerebellum.


2021 ◽  
Vol 34 (1) ◽  
pp. 139-146
Author(s):  
Elham K. Nasser ◽  
Kithar R. Majeed ◽  
Hayder I. Ali

Fortified milk containing Lactobacillus plantarum, L. casei, and L. acidophilus isolates and their mixture were used in dosing the male albino rats at an age of 9-12 weeks at an average of 23 g with induced hypothyroidism at a concentration of 0.6 g.kg-1 of carbimazole. Total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) were estimated. The results showed a significant increase in the level of triglycerides (TG), cholesterol and triglycerides. Low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL), with a significant decrease in the level of high-density lipoprotein (HDL) in infected male mice, compared to the control sample, and upon dosing with liquid milk fortified, it returned to its normal level without significant differences from the control group.


2021 ◽  
Vol 9 (2) ◽  
pp. 450-464
Author(s):  
Renu Tripathi ◽  
Swati Agarwal ◽  
Syed Ibrahim Rizvi ◽  
Neetu * Mishra

Mercury is a harmful toxic pollutant, which has hepato-nephrotoxic, hematotoxic, genotoxic and neurotoxic, effects. The aim of the study was to evaluate the protective efficacy of wheatgrass on mercuric chloride (HgCl2) induced oxidative stress and associated complications in rat model. Albino rats were divided into four groups (three rats per group). Group I normal control group. Group II oxidative stressed group received mercuric chloride (0.5 mg/kg/day). Group III only received wheatgrass extract (100 mg/kg/day), whereas Group IV received wheatgrass (100 mg/kg/day) after one hour, followed by mercuric chloride (0.5 mg/kg/day) for 30 days. The results of the study showed that wheatgrass supplementation significantly decreased the HgCl2 induced elevated oxidative stress parameters Plasma Malondialdehyde (MDA) content, Plasma membrane redox system (PMRS), Advanced oxidation protein products (AOPP), simultaneously elevated lipid profile (Total Cholesterol, Triglycerides, Low-density lipoprotein (LDL), liver enzymes as, Plasma Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), and Alanine aminotransferase (ALT), Serum Urea, and Creatinine levels in rats. In addition, wheatgrass treatment improved the antioxidant status in terms of intracellular Reduced Glutathione (GSH), Ferric reducing antioxidant power (FRAP) and 2, 2- diphenyl -1- picrylhydrazyl (DPPH). Therefore it can be concluded that wheatgrass has great potential to diminish the stress-mediated complications and improve the antioxidant status.


2012 ◽  
Vol 57 (No. 6) ◽  
pp. 287-292 ◽  
Author(s):  
AS Durmus ◽  
M. Yaman ◽  
HN Can

These experiments were conducted in order to compare the effects of extractum cepae, heparin, allantoin gel (CTBX) and silver sulfadiazine (SSD) cream on burn wound healing in rats. Thirty six adult, female Wistar albino rats were divided into three equal groups. A burn was made on the back of all rats. The burned areas in the first, second and third groups were covered with cold cream (control), SSD skin cream and CTBX twice a day, respectively. Seven and 14 days later, the rats were sacrificed and burned skin tissue samples were collected from the rats for histopathological examinations. Histopatological evaluations on the 7<sup>th</sup> and 14<sup>th</sup> days showed burn healing to be better in the CTBX and SSD groups with respect to the control group. The best burn wound healing was observed in the CTBX group (P &lt; 0.001). Wound healing was significantly different between the groups at days 7 and 14 (P &lt; 0.001). In conclusion, application of CTBX has significant positive effects on the healing of burn wounds in a rat model. &nbsp;


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Andrew K. Davey ◽  
Jessica Hayward ◽  
Jean K. Marshall ◽  
Anthony E. Woods

Aim. The aim of this investigation was to examine the alterations in the peritoneum after cold dry CO2, heated dry CO2, and humidified heated CO2at pressures equivalent to intraperitoneal pressures used in human laparoscopy.Methods. Eighteen rats were divided into 4 treatment groups—group 1: untreated control; group 2: insufflation with cold dry CO2; group 3: insufflation with heated, dry CO2; group 4: insufflation with heated and humidified CO2. The abdomen was insufflated to 5 mm/Hg (flow rate 50 mL/min) for 2 h. Twelve hours later, tissue samples were collected for analysis by light microscopy (LM) and scanning electron microscopy (SEM).Results. Group 1: no abnormalities were detected. Group 2: specimens revealed an inflammatory response with loss of mesothelium and mesothelial cell nuclei showing lytic change. Cells were rounded with some areas of cell flattening and separation. Group 3: some animals showed little or no alteration, while others had a mild inflammatory response. Mesothelial cells were rounded and showed crenation on the exposed surface. Group 4: specimens showed little change from the control group.Conclusions. The LM results indicate that insufflations with heated, humidified CO2are the least likely to induce mesothelial damage.


2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Yasar Yildirim ◽  
Esma Gulsum Cellad ◽  
Ali Veysel Kara ◽  
Zülfükar Yilmaz ◽  
Ali Kemal Kadiroglu ◽  
...  

Our aim was to evaluate effect of etanercept on oxidative stress parameters in rats with experimental peritonitis and investigate the availability of etanercept usage in the treatment of peritonitis in the future. Twenty-eight rats were divided into four groups as control (group 1), peritonitis (group 2), peritonitis + cefazolin sodium (group 3), and peritonitis + cefazolin sodium + etanercept (group 4). Peritoneal tissue and blood samples were taken from all of the rats for histopathological and biochemical examination. The oxidative stress parameters were examined in blood and tissue samples. It was observed that rats with peritonitis benefit from cefazolin sodium treatment. Evaluating the effectiveness of etanercept was our main objective for this study. In this perspective, we compared group 3 and group 4 and found statistically significant decreases in oxidative parameters and statistically significant increases in antioxidants in serum and tissue samples in group 4. It is observed that there was a significant contribution of etanercept on biochemical and also histopathological results. As a result, the TNF-αinhibitor, etanercept, in addition to antibiotics given in the early treatment of peritonitis results in more significant improvement of histopathological and oxidative parameters as compared to antibiotics alone.


Sign in / Sign up

Export Citation Format

Share Document