Histopathological Changes in Liver Tissue after repeated administrations of an Intermediate Dose of Coenzyme Q10 to Wistar Rats

Author(s):  
Ali G. Abdullah ◽  
Ban I. Sedeeq ◽  
Marwan S. Azzubaidi

Coenzyme Q10 (Co-Q10) or ubiquinone plays an important role in the cellular metabolism. The safety profile of ubiquinone as a dietary supplement has been assessed in few sub-chronic toxicity studies. The aim of this study was to evaluate the possible hepatotoxic effect of long-term oral administration of an intermediate oral dose of Co-Q10 in experimental animals. Fifteen Wistar rats were treated with 300mg/kg daily oral doses of Co-Q10 using forced oral feeding for six weeks. Additional 5 healthy rats represented the control group for comparison. All rats were euthanized at the end of the 6th week. Then H and E stained histological sections of rats’ livers revealed vacuolation of hepatocytes, an increase in the diffusion of macrophages and the formation of microgranuloma most probably indicating a drug-induced injury. In conclusion, this study adds evidence supporting the potential hepatotoxic actions resulting from repeated administration of intermediate oral dose of Co-Q10 especially on the long-term.

2010 ◽  
Vol 29 (4) ◽  
pp. 297-302 ◽  
Author(s):  
E. Madrigal-Bujaidar ◽  
Y. Cárdenas García ◽  
I. Álvarez-González

Imipramine (IMI) and desipramine (DES) are two drugs widely used for the treatment of depression as well as for other diseases. In the present study, we determined their capacity to induce chromosomal aberrations in mouse bone marrow cells. Three doses of each compound were tested and their results were compared with the frequency of chromosomal aberrations obtained in a control group as well as with a group treated with cyclophosphamide. Our results showed a significant increase in chromosome damage with the doses tested for each compound: 7, 20, and 60 mg/kg in the case of IMI, and 2, 20, and 60 mg/kg as regards DES. This last drug induced stronger chromosomal damage than IMI. Our results agree with previous studies regarding the induction of micronuclei and sister chromatid exchanges by the drugs in mouse and suggest caution with respect to their use in long-term treatments.


2012 ◽  
Vol 36 (1) ◽  
pp. 145-156
Author(s):  
Falah Muosa Kadhim Al-Rikabi

The effects of oseltamivir administration, an anti influenza viruses A and B, on somefunctional parameters of rat liver were investigated, to evaluate the possible hepatotoxiceffect. Eighteen (18) wister male albino rats with body weight ranged 150-190 gm weredivided into three groups, the first group(T1) was treated orally with 1mg/kg.BW astherapeutic dose of Oseltamivir for 7consuctive days. The second group (T2) wastreated with the same dose for six weeks, while the control group dosed distill water.The results revealed, there was a significant increase in the onset of barbiturate sleepingtime and a significant p ≤ 0.05 decrease of the duration of barbiturate sleeping time ofthe T2 rats . The liver enzymes activity revealed a significant decrease in ALT in T1rats and significant increased p<0.05 in the T2 rats, while the AST activity showed onlysignificant increased p<0.05 in the T2 treated rats. The activity of ALP was p<0.05significantly increased in the rats of treated groups. The blood sugar was significantlydecreased p<0.05 only in the T2rats. Cholesterol level was significantly p<0.05increased in T2 treated rats, while the serum of both treated groups showed asignificantly increase p<0.05 in the triacylglycerol concentration.The HDL level was significantly decreased p<0.05 only in theT1 rats. The treated T2rats showed a significant decrease p<0.05 in the LDL, while the VLDL level revealed asignificant increase p<0.05.The total serum protein level was significantly increasedp<0.05 in the rats of T2. Liver histopathological lesions of the T1rats revealed largeamount of suppurative exudates, severe dilation and congestion of central veins andsinusoids with activation of kupffer cells. The liver of T2 rat showed multiple areas offocal necrosis, fibrous thickening of Glisson capsule with vacuolar degeneration ofhepatic parenchyma. In:conclusion, Oseltamivir has hepatotoxic effect in rats treatedwith therapeutic dose 1mg/ kg.BW. orally in different periods.


2018 ◽  
Vol 65 (2) ◽  
pp. 1-3
Author(s):  
M. Dragún ◽  
G. Dóka ◽  
M. Máťuš ◽  
P. Křenek ◽  
J. Klimas

Abstract Aim: The aim is to identify the possible changes in the expression of genes, that regulate calcium homeostasis in cardiomyocytes in diabetes mellitus. Methods: Male Wistar rats were randomized into two experimental protocols: short-term 5-days streptozotocin-induced diabetes protocol with 20 weeks old animals at the end of the protocol (total N = 20) and long-term 4-weeks protocol with 18 weeks of age at the end of the protocol (total N = 38). 50 mg/kg of streptozotocin (STZ) was administered in both protocols by a single intraperitoneal injection in 0,1M citrate buffer (pH = 4.5). Control group (CON) received only vehiculum. Gene expressions in samples of left heart ventricle were measured by RT-qPCR method. Results: The expression of SERCA2a in short-term protocol was decreased. In long-term protocol, decreased SERCA2a, TRPC4 and TRPC6 mRNA levels were observed (*p < 0.05). SERCA2a and TRPC4 mRNA levels exhibited statistical monotonic correlation in STZ-treated group in long-term protocol. Conclusions: In diabetes mellitus, the calcium homeostasis in cardiomyocytes is altered and there could be a relation between alteration of internal sarcoplasmatic stores and store-operated calcium entry.


2018 ◽  
Vol 46 (1) ◽  
pp. 8
Author(s):  
Minoo Azani ◽  
Asghar Moshtaghie ◽  
Ali Asghar Rastegari

Background: One of the valuable tests for diagnosis of cardiovascular and liver diseases is measuring of AST activity. One of the main enzymes of transaminases group is aspartate aminotransferase. Previous Studies have shown that some alteration may occur in mitochondria function as the result of different disease or taking different medication; these changes in mitochondrial and cytosolic AST isozymes can be the sign of disorders. According to the role of steroid hormone in induction of its effects on protein synthesis genes, this study is conducted to shed some light on mechanisms and the interference of steroid hormones and antibiotics.Materials, Methods & Results: In this study, male Wistar rats were injected intramuscularly with Testosterone, progesterone and estradiol; while tetracycline and streptomycin injections were intraperitoneal. Testosterone, progesterone and estradiol injections were carried out in a short-term (15 days) and long-term (45 days) periods. Steroid hormones were dissolved in sesame in a way that by each injection, 0.2 mL sesame oil (containing specific amount of hormone) was injected to the rat. Control group was kept in the same condition except that their sesame oil injection contained no hormone. Tetracycline and Streptomycin injection was carried out for 5 days at 7 am and pm, at 50 mg/kg dosage intraperitoneally. In short- and long-term periods, rats were divided into four groups of 6-member. The concentrations were the same in the periods and 0.2 mL sesame oil was injected intramuscularly. 1 mg testosterone, 12 mg progesterone and 0.2 mg estradiol were intramuscularly injected to rats in group 2, 3 and 4, respectively [10]. Rats were divided into 9 six-member groups as follows: Group 1: intraperitoneal injection of 0.2 mL physiological serum; group 2: injection of 1 mg testosterone; group 3: injection of 1 mg testosterone + 50 mg/kg streptomycin; group 4: injection of 1 mg testosterone + 50 mg/kg tetracycline; group 5: injection of 0.2 mg estradiol; group 6: injection of 0.2 mg estradiol + 50 mg/kg streptomycin; group 7: injection of 0.2 mg estradiol + 50 mg/kg tetracycline; group 8: injection 50 mg/kg streptomycin; and group 9: injection of 50 mg/kg tetracycline. Serum concentration of AST enzyme was measured at the end of each period and the data were compared by SPSS software. all three steroid hormones had no significant impact on AST activity in short term. However, a significant effect was observed in long term in mean AST activities of the 4 groups. The group injected by testosterone exhibited 9% increases in comparison with the control group. Antibiotic-administrated groups showed lower activities as compared with hormone-injected groups. Steroid hormones and testosterone can enhance AST activity, in short-term and long-term, respectively by induction of protein enzyme. The second test confirmed this theory as the antibiotics decreased the AST activity enhancement by testosterone.Discussion: Based on the present study, steroid hormones can enhance the aspartate aminotransferase activity; and antibiotics can decrease the level of this liver enzyme by inhibition of polypeptide synthesis on related genes. This reaction could be due to interference of hormones and antibiotics effect which hinders the hormone effect along with the drug to activate the protein synthesis process.


Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1487
Author(s):  
Eva Greibe ◽  
Ole Nymark ◽  
Sergey Fedosov ◽  
Christian Heegaard ◽  
Ebba Nexo

Foods contain natural vitamin B12 forms, such as hydroxo–B12 (HO–B12), whereas vitamin pills contain the synthetic cyano–B12 (CN–B12). Recent studies in rats showed different tissue distributions of CN–B12 and HO–B12 24 h after oral administration. Here, we investigate whether these differences are sustained or leveled out with time in both B12-deplete and -replete rats, thereby assessing if the two forms are equally good at maintaining a normal B12 status. Male Wistar rats were fed diets with low (n = 16) or high (n = 12) B12 content for 17 days. At day 10, the rats received a single oral dose of [57Co]-labeled CN–B12 or HO–B12 (n = 6 and n = 8, respectively, in each diet group). The rats were sacrificed on day 17 and endogenous B12 and [57Co]–B12 were measured in liver, kidney, and plasma. We found that the low-B12 diet introduced a B12-deplete state as judged from medians of endogenous B12 compared to rats on a (high-B12 diet): Plasma (565 (1410) pmol/L), liver (28.2 (33.2) pmol/g), and kidneys (123 (1300) pmol/g). One week after oral administration, the labeled B12 was distributed as follows: HO–B12 > CN–B12 (liver) and CN–B12 > HO–B12 (kidneys, plasma). The tissue/plasma ratios showed different equilibriums for labeled CN–B12 and HO–B12 in the B12-deplete and -replete groups. The equilibrium of endogenous B12 resembled [57Co]CN–B12 in replete rats but differed from both [57Co]CN–B12 and [57Co]HO–B12 in deplete rats. The data suggest long-term differences in tissue utilization of the two B12 forms and warrant further studies concerning the possible benefits of consuming HO–B12 instead of CN–B12 in oral B12 replacement.


Author(s):  
ZUBERU JIBRIL ◽  
SANI SANUSI

Objective: The study investigated changes in haemostatic parameters such as; bleeding time, blood clotting time and differential platelet counts of wistar rats following repeated administration of aqueous extract of allum cepa L. Methods: Rats were divided into four groups of four animals each (n=4). Group I served as normal control, Group II, group IIIand group IV were administered 25 mg/kg bw, 50 mg/kg bw and 100 mg/kg bw of the extract intra-peritoneally for two weeks, respectively. After 14 d experimental period, blood samples were collected for the determination of bleeding time, clotting time and differential platelet count. Results: The findings of this study revealed a significantly increased (p<0.05) clotting time at a dose of 25 mg/kg but showed no significant change in bleeding time and differential platelet count of all the groups. Conclusion: Aqueous extract of brown onion showed anti haemostatic effect in albino rats by increasing clotting time at a lower dose.


2003 ◽  
Vol 46 (4) ◽  
pp. 171-174 ◽  
Author(s):  
Michaela Adamcová ◽  
Martin Štěrba ◽  
Ivona Klimtová ◽  
Tomáš Šimůnek ◽  
Radomír Hrdina ◽  
...  

Both cardiac troponin T (cTnT) and cardiac troponin I (cTnI) are considered to be reliable biomarkers with sufficient sensitivity and specificity for cardiac injury in the majority of laboratory animals. The aim of our study was to compare the diagnostic performance of cTnT and cTnI in three groups of rabbits: 1) control (saline 1 ml/kg i.v.); 2) Salicylaldehyd Isonicotinoyl Hydrazone – SIH (50 mg/kg, once weekly, i.p.; partially dissolved in 10 % Cremophor solution); 3) 10 % Cremophor solution in water (2 ml/kg i.v.). The drugs were given once a week, 10 administrations. The concentration of cTnT was measured using Elecsys Troponin T STAT Immunoassay (Roche). The concentration of cTnI was measured using AxSYM Troponin I (Abbott). The linear regression model was applied to see if there is a dependence between cTnT and cTnI. The coefficient of determination was not acceptable in all groups. The highest value of R2was found in the control group (R2= 0.424). We may conclude that in rabbits meaningful dependence between cTnT and cTnI was not found. According to our long-term experiences cTnT seems to be more suitable cardiomarker in rabbits in comparison with cTnI where the data are characterized by the large scatter.


2020 ◽  
Vol 4 ◽  
pp. 239784732093150
Author(s):  
Godwin Okwudiri Ihegboro ◽  
Adamu Jibrin Alhassan ◽  
Chimaobi James Ononamadu ◽  
Mohamed Sani Sule

The pharmacological effects of medicinal plants are due to the presence of certain chemical compounds present in them. Previous studies have shown that crude extracts of Tapinanthus bangwensis ( T. bangwensis) possess hepatocurative potential. However, the present study aims on evaluating the antioxidant activity as well as identifying the chemical compounds in ethylacetate fraction of T. bangwensis that ameliorate carbon tetrachloride-induced hepatotoxicity in Wistar rats. Six subfractions of ethylacetate fraction were obtained by column chromatography. The antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazine (DPPH), biochemical assay determined by spectrophotometry, and compound elucidation by liquid chromatography–mass spectroscopy (LC-MS) analysis. The DPPH result shows that subfraction F0 exhibited the strongest antioxidant activity followed by F4 while F1 exhibited the lowest. Oral administration of 100 mg/kg body weight of the subfractions of ethylacetate fraction of T. bangwensis increases superoxide dismutase and catalase activities and also glutathione level and decreases malondialdehyde level compared to the positive control group. Subsequently, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, and conjugated bilirubin were reduced while albumin and total protein levels increased compared to the positive control group. However, there were no significant differences between the positive control group and the group induced and treated with the subfractions at p < 0.05. The histopathology study shows normal hepatocyte distribution with no fat deposit in the induced and treated groups while fatty liver was observed in the positive group. The anti-hepatotoxic effect was higher in F4 than in other subfraction treated groups. Hence, the LC-MS analysis of F4 reveals the presence of 8-hydroxyluteolin-8-glucoside, Avicularin, Fisetin-7-glucoside, Isoscutellarein-7-xyloside, and Isovitexin, respectively, and has been reported to exhibit antioxidant and hepatocurative activities. It can be concluded that the hepatocurative effect could be due to the chemical compounds identified above.


2019 ◽  
Vol 9 (3) ◽  
pp. 26-32
Author(s):  
Swatilekha Maiti ◽  
Saswati Parua ◽  
Dilip Kumar Nandi ◽  
Keshab Chandra Mondal ◽  
Saptadip Samanta

Tuberculosis is one of the serious airborne infectious diseases. Rifampicin is commonly used as anti-tuberculosis drug which creates drug-induced hepatotoxicity. Physiologically, liver maintains metabolic homeostasis and also regulates the detoxification process. The study of rifampicin mediated hepatotoxicity had been performed on male albino rat after its oral administration with a dose of 50 mg/kg body weight/day for 14 days. Several biochemical markers like serum glutamate pyruvate tranaminase (AST), serum glutamate oxaloacetate transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), serum total protein, serum bilirubin, serum cholesterol were considered to evaluate the toxicity. Significant elevation of level of AST (115.89%), ALT (134.40%), ALP (46.15%), serum cholesterol (91%) and bilirubin content (119.44%) had been observed in treated group compared with control group. High level of MDA content as lipid peroxidation marker was also been noticed in drug induced group. Histopathological studies had shown the disintegrated hepatolobular structure with dilated central vein. All these findings indicated that the selected dose of rifampicin is hepatotoxic; proper monitoring and care are essential during the treatment of tuberculosis. Keywords: rifampicin; hepatoxicity; anti-tuberculosis


2018 ◽  
Vol 3 (1) ◽  
pp. 37-42
Author(s):  
Dr Aigbe Gregory Ohihoin

Background: Patients with HIV AIDS are beginning to live longer and healthier lives due to the use of ARV therapy. The effect of long term usage of these agents on the reproductive potential of human females has not been well studied. The study of the estrus cycle in rats will give information on the possible effect of ARV's on the reproductive potential of humans.Aims: To elucidate the effects of the first-line ARV's, Efavirenz, Tenofovir and Lamivudine administered in a combined fashion, on the oestrous cycle of adult female Wistar rats.Material and Methods: Twenty-five female Wistar rats with a mean weight of 158.76g were used. A total of five groups of rats were involved in the study. Five rats were apportioned to each study group. All three ARV's were administered orally in a combined fashion to a particular group of Female Wistar rats and also administered individually to other groups while the control group received water. The estrous cycles of various groups of rats were monitored via microscopic analysis of their vaginal smearsResults: The control group had a consistently regular cycle, while the cycles of the rats in the combination therapy group and the rats that received efavirenz alone, became elongated relative to the control group. There was a 48-hour enlongated proestrous phase some of the rats.Conclusions: First-line ARV's - Tenofovir, Efavirenz, and Lamivudine- disrupt the estrous cycle of adult rats. Further investigation of the long term usage of these drugs on the menstrual cycle of human females is therefore necessary


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