A nutrient mixture suppresses carbon tetrachloride–induced acute hepatic toxicity in ICR mice

2008 ◽  
Vol 27 (7) ◽  
pp. 559-566 ◽  
Author(s):  
MW Roomi ◽  
T Kalinovsky ◽  
NW Roomi ◽  
V Ivanov ◽  
M Rath ◽  
...  

We examined the effect of a nutrient mixture (NM) that contains lysine, proline, ascorbic acid, and green tea extract in mice treated with carbon tetrachloride (CCl4), a model of liver injury in which free radical, oxidative stress, and cytokine production are closely linked. Seven-week-old male Imprinting Control Region (ICR) mice were divided into four groups (A–D) of five animals each. Groups A and C mice were fed a regular diet for 2 weeks, whereas groups B and D mice were supplemented with 0.5% NM (w/w) during that period. Groups A and B received corn oil i.p., whereas groups C and D received CCl4 (25 μL/kg, in corn oil, i.p.). All animals were killed 24 h after CCl4 administration, serum was collected to assess liver and kidney functions, and livers and kidneys were excised for histology. Mean serum aspartate aminotransferase and alanine aminotransferase were comparable in groups A and B, increased markedly in group C, and significantly lowered in group D compared with group C. CCl4 had no significant effect on renal markers (blood urea nitrogen [BUN], creatinine, and BUN/creatinine ratio). CCl4 administration caused an intense degree of liver necrosis that was less severe in the NM fed group D. These results indicate that NM could be a useful supplement in preventing acute chemical-induced liver toxicity.


2008 ◽  
Vol 27 (3) ◽  
pp. 223-230 ◽  
Author(s):  
MW Roomi ◽  
T Kalinovsky ◽  
V Ivanov ◽  
M Rath ◽  
A Niedzwiecki

Acetaminophen (APAP) overdose is often fatal, leading to fulminant hepatic and renal tubular necrosis in humans and animals. We studied the effect of a nutrient mixture (NM) containing, among other nutrients, lysine, proline, ascorbic acid, N-acetyl cysteine, and green tea extract, which has previously been demonstrated to exhibit a broad spectrum of therapeutic properties on APAP-induced hepatic and renal damage in ICR (Imprinting Control Region) mice. Seven-week-old male ICR mice were divided into four groups (A–D) of five animals each. Groups A and C mice were fed a regular diet for 2 weeks, while groups B and D mice were supplemented with 0.5% NM (w/w) during that period. Groups A and B received saline i.p., while groups C and D received APAP (600 mg/kg) i.p. All animals were killed 24 h after APAP administration, serum was collected to assess the liver and kidney functions, and the livers and kidneys were excised for histology. Mean serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, BUN (Blood Urea Nitrogen), creatinine, and BUN/creatinine ratios were comparable in groups A and B, increased markedly in group C and significantly lower in group D compared with group C. APAP caused significant centrilobular necrosis and glomerular damage in unsupplemented animals, while NM prevented these alterations. The results indicate that NM has potential to protect against APAP-induced liver and kidney damage.



2021 ◽  
Vol 19 ◽  
pp. 205873922110008
Author(s):  
Meng Chen ◽  
Xinyan Song ◽  
Jifang Jiang ◽  
Lei Xing ◽  
Pengfei Wang

To investigate the protective effects of galangin on liver toxicity induced by carbon tetrachloride (CCl4) in mice. Mouse hepatotoxicity model was established by intraperitoneal injection (i.p.) of 10 ml/kg body weight CCl4 that diluted with corn oil to a proportion of 1:500 on Kunming mice. The mice were randomly divided into five groups named control group, model group, and 1, 5, and 10 mg/kg galangin group. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed by ELISA. Liver histopathological examination was observed via optical microscopy. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and glutathion (GSSG) were analyzed to assess oxidative stress. Finally, western blot assay was carried out to analyse the expression levels of total AMP-activated protein kinase (AMPK), phospho-AMPK (p-AMPK), total liver kinase B1 (LKB1), and phospho-LKB1 (p-LKB1). Compared with the control group, in the model group, the levels of AST, ALT, MDA, and GSSG increased significantly ( p < 0.01); the activity of SOD and GSH decreased significantly ( p < 0.01); and the histopathological examination revealed liver necrosis. However, treatment with galangin (5 and 10 mg/kg) significantly reversed these CCl4-induced liver damage indicators. Furthermore, treatment with galangin (10 mg/kg) significantly increased the p-AMPK and p-LKB1 expression levels ( p < 0.01). This study supports the hepatoprotective effect of galangin against hepatotoxicity, perhaps occurring mainly through the LKB1/AMPK-mediated pathway.



1996 ◽  
Vol 15 (5) ◽  
pp. 381-393
Author(s):  
Robyn B. Blain ◽  
Manoj Moholkar ◽  
Kamala Lakshmanan ◽  
Denise Leonard ◽  
Xiaoqiang Zhao ◽  
...  

A series of experiments was conducted to assess the effects of prior dosing and/or multiple modest blood withdrawal on subsequent carbon tetrachloride (CCl4)-induced hepatotoxicity. Adult male Wistar rats were randomly assigned to the following treatments: oil-CCl4, oil-bleed-CCl4, CCl4-CCl4, and CCl4-bleed-CCl4, with bleed groups having 1 ml of blood removed at baseline (time 0), 24, 48, 72, and 120 h. At these times the levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined. The serum enzyme levels of the CCl4 (0.9 ml/kg, vol/vol in corn oil, per os) treated rats (treated at time 0) had returned to untreated levels prior to the administration of the second dose (120 h). Serum enzyme (AST/ALT) levels were measured again 24 and 48 h after the second CCl4 (0.9 ml/kg, 1:1 vol/vol in corn oil, per os) treatment. The results indicated that the prior dose of CCl4 (0.9 ml/kg, 1:1 vol/vol in corn oil, per os) enhanced the hepatotoxicity of a subsequent identical dose of CCl4 three- to six-fold when the two doses were separated by 2–14 days, although the prior dose was protective when administered 24 h before the second dose. Prior multiple blood drawing also enhanced the hepatotoxicity of a subsequent dose of CCl4 (0.9 ml/kg, 1:1 vol/vol in corn oil, per os) three-fold. The effect of blood drawing has been demonstrated to cross sex and strain when tested on male and female Sprague-Dawley and Wistar rats. The combination of the two procedures (with the two CCl4 doses separated by 5 days) enhanced the hepatotoxicity of a subsequent identical dose of CCl4 (0.9 ml/kg, 1:1 vol/vol in corn oil, per os) 10-fold. Subsequent sham bleed experiments indicated that the increase in serum enzyme levels previously associated with blood withdrawal is substantially associated with the handling (i.e. stress) involved in blood withdrawal rather than the removal of modest amounts of blood per se.



Author(s):  
Anupama Dhavaleshwar ◽  
Bharti Chogtu ◽  
Deepak Nayak ◽  
Praveen Kumar S. E.

Background: The clinical studies have shown contrary results regarding hepatoprotective effect of statins. However, antifibrotic properties of statins in in vitro and in vivo experimental models have been demonstrated. The purpose of this study was to assess and compare the effect of statins on serum liver enzymes and their antifibrotic effects.Methods: Forty two rats were divided into 7 groups (I to VII) (n=6). Liver toxicity was induced by injecting carbon tetrachloride (1 ml/kg). Control groups received corn oil (0.1 ml/100 gm) and carboxy methyl cellulose (0.50%) respectively. Group III to VII received carbon tetrachloride (CCl4) for 6 weeks and then groups IV, V, VI and VII received simvastatin (10 mg/kg), atorvastatin (15 mg/kg), rosuvastatin (2 mg/kg) and silymarin (50 mg/kg) for another 8 weeks respectively. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels were estimated in all the groups at baseline, 6 weeks and 14 weeks. At 14 weeks, histopathology of liver was done in all groups.Results: At 14 weeks, all the test groups (IV, V and VI) showed a significant decrease in serum ALT, AST and ALP levels as compared to control (p<0.05) and group III (p<0.05). On intergroup comparison, liver enzymes in rats in group VI (rosuvastatin) and group V (atorvastatin) were decreased more in comparison to group IV (simvastatin) but the difference was not statistically significant except for AST levels where the difference was significant between the statins. There was decrease in hepatic fibrosis by statins with rosuvastatin being superior followed by atorvastatin and simvastatin.Conclusions: In the present study statins decreased the serum AST, ALT and ALP levels and histopathological changes were reversed by statins in CCl4 induced hepatotoxic models.



2021 ◽  
Vol 20 (10) ◽  
pp. 2089-2097
Author(s):  
Ukamaka U. Eze ◽  
Ifeanyi G. Eke ◽  
Aruh O. Anaga ◽  
Elias Abah ◽  
Ikechukwu J. Udeani ◽  
...  

Purpose: The recent ceftriaxone-induced anaemia and mortalities at the dose of 50 mg/kg in Veterinary Teaching Hospital, University of Nigeria prompted this study which sought to assess the clinicotoxicological effects of ceftriaxone (CFZ) after intramuscular administration of graded doses in Basenji dogs.Methods: The effects of CFZ on the haematological indices, physiological parameters, liver and kidney functions were assessed in 4 group of dogs (n = 4) designated A – D. They were given CFZ intramuscularly for 21 days at doses of 12, 25 and 50 mg/kg for groups A, B, C, respectively, while thecontrol (group D) received the diluent (lignocaine 0.2 mL)Results: The mean pulse and heart rate of dogs in group C were significantly (p < 0.05) higher than those of group A, B and D. Significant (p < 0.05) decrease in red blood cell count (RBC), haemoglobin concentration (Hb) and packed cell volume (PCV) was observed in group C on days 7 and 14, while on day 21, these parameters were significantly (p < 0.05) higher in group D than in the treated groups. On day 14 of CFZ administration, the alanine transaminase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities of dogs in group C was significantly (p < 0.05) elevated than the control group.Conclusion: These findings suggest that CFZ, at the doses of 12.5 - 25 mg/kg, appears safe in dogs as most of the adverse effects observed are reversed following the withdrawal of the drug on day 28. However, CFZ at 50 mg/kg causes anaemia, tachycardia and bilateral paralysis of the hind limbs which did not revert to normal after one week; hence, it is not recommended for use in dogs at this dose.





Author(s):  
Nurgozhin T. ◽  
Sergazy S. H. ◽  
Adilgozhina G. ◽  
Gulyayev A. ◽  
Shulgau Z. ◽  
...  

Objective:This study investigates the hepatoprotective effect and the antioxidant role of polyphenol concentrate in the experimental model of carbon tetrachloride (CCl4) induced toxicity. Methods: Antioxidant activity of Cabernet Sauvignon grape polyphenol were evaluated by radical scavenging of 1,1-diphenyl-2-picryl hydrazyl radical (DPPH), 2,2’-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS.+). In addition, the effects of polyphenol concentrate on the survival of Wistar rats in the toxicity model, was also investigated. The polyphenol concentrate was administered for 5 five days prior to injection of carbon tetrachloride in a sub-lethal dose of 300 mg/kg of animal body weight in order to perform histological examinations of the liver and kidney, and detect the levels of AST, ALT and bilirubin. Results: Administration of polyphenol concentrate increased animal survival in the experimental model. Moreover, the intragastric administration of polyphenol concentrate prior to the initiation of the experimental model of toxicity, which was caused by a sub-lethal CCl4 dose, reduced morphological injuries in the liver and kidney, decreased the AST and ALT levels of the blood serum. Discussion and conclusion: Our data demonstrate that polyphenol concentrate possesses an antioxidant potential both in vitro and in vivo by reducing antioxidant stress that was caused by CCl4 administration into rats.



2020 ◽  
Author(s):  
Firdous Beigh ◽  
Nidda Syeed ◽  
Walaa Saeed ◽  
Ziab Alahmadey ◽  
Ibrahim Seedi

BACKGROUND Coronavirus disease (COVID-19) is a budding infectious disease that has affected various countries globally. OBJECTIVE The aim of this study was to analyze the effect of COVID-19 disease on liver and kidney functions and to determine their association with the severity and mortality of disease METHODS A total of 100 confirmed COVID-19 adult patients from Madinah city of Saudi Arabia hospitalized between April 28, and June 30, 2020 were included,and categorized into asymptomatic,mild to moderate and severely ill patients.We analyzed the clinical status of liver and renal functioning in all of the three groups. RESULTS The majority of patients (51%) were diagnosed with mild to moderate disease, 27% of patients were severely ill and 22% of patients were asymptomatic.The liver and renal functional analysis showed that the severity of the COVID-19 patients were significantly associated with the kidney and renal impairments exhibiting higher levels of ALT, AST, Creatinine, Urea levels (P < 0.05). Furthermore, in this study, a novel association is found between high Na and Cl levels with the severely ill COVID-19 patients. CONCLUSIONS We concluded from the present study that a significant percentage of COVID-19 patients continued to have a normal liver and renal function during the course of their disease. Nevertheless, severely ill COVID-19 patients were more prone to have abnormal liver and renal functions. During the course of treatment, the patients had a gradual normalization of their liver and kidney parameters and subsequently achieved a complete normal liver and renal functions upon discharge with no mortality.



1997 ◽  
Vol 3 (S2) ◽  
pp. 51-52
Author(s):  
B.J. Cornell ◽  
A. Singh ◽  
I. Chu

Polyhalogenated aromatic compounds such as polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins (PCDDs) continue to be environmental contaminants because of their bioaccumulation in the food chain and high resistance to biodegradation. The current study was undertaken to determine if a mixture of PCB congeners (WHO-IPCS) were interactive with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in producing morphological changes in the rat liver. Both compounds are known to produce a broad range of biochemical and morphological alterations including enzyme induction.Groups (N=5) of female Sprague-Dawley rats were administered TCDD (0, 2.5, 25, 250, 1000 ng/kg bw/day) or PCB (0, 2, 20 μg/kg bw/day) alone, or in combination with each concentration of both compounds. Incorrect concentrations were published in a previous abstract. The test substance was mixed with corn oil and given by gavage at 2 ml/kg daily for 28 days. At the end of the experiment, the rats were killed and liver samples were prepared for transmission electron microscopy.



1976 ◽  
Vol 67 (1) ◽  
pp. 103-105 ◽  
Author(s):  
M. Hino ◽  
H. Fuyamada ◽  
T. Nagatsu ◽  
S. Kurokawa ◽  
S. Okuyama


Sign in / Sign up

Export Citation Format

Share Document