Acutely applied melatonin prevents CCl4-induced testicular lesions in rats: the involvement of the oxidative capacity and arginine metabolism

Abstract Carbon tetrachloride (CCl4) represents an organic chemical that causes reactive oxygen species derived organ disturbances including male infertility. Melatonin (MLT) is a neurohormone with strong antioxidant capacity, involved in numerous physiological processes. In this study we evaluated the capability of MLT, administered in a single dose of 50 mg/kg, to preserve the testicular tissue function after an acute administration of CCl4 to rats. The disturbance in testicular tissue and the effects of MLT after CCl4 exposure were estimated using biochemical parameters that enabled us to determine the tissue (anti)oxidant status and the intensity of arginine/nitric oxide metabolism. Also, the serum levels of testosterone and the histopathological analysis of tissue gave us a better insight into the occurring changes. A significant diminution in tissue antioxidant defences, arginase activity and serum testosterone levels, followed by the increased production of nitric oxide and extensive lipid and protein oxidative damage, was observed in the CCl4-treated group. The application of MLT after the CCl4 caused changes, clearly visible at both biochemical and histological level, which could be interpreted mainly as a consequence of general antioxidant system stimulation and a radical scavenger. On the other hand, the application of MLT exerted a limited action on the nitric oxide signalling pathway.

[ protective effects of Iranian golpar [Heracleum persicum] essential oil in liver damages induced by CCl4 in Wistar rats]

Background: Nowadays, liver disorders are one of the most serious and threatening problems of the health. Persian Golpar [Heracleum [H.] persicum] as an endemic medicinal plant with antioxidant and anti-inflammatory properties was used [noted] in the study for reducing the live injuries

Objective: This experiment -for the first time- was conducted to consider the effects of the oils obtained from fruits of Persian Golpar on the liver toxicity induced by the injection of tetrachloride carbon [CCl4] in the Wistar rats

Methods: In this study, 100 male Wistar rats were divided into 20 groups [n=5]. Negative control group [NC] received DMSO and olive oil for two weeks and the positive control group [C] received DMSO as i.p injection in 14 days following CCl4 [2 ml/kg b.w] at day 15th. The standard group [BHT], The treatment groups received H. persicum essential oils at both doses 100 and 200 mg/kg b.w as i.p injection following CCl4 [2 ml/kg b.w] at day 15th. Then, the levels of the glutathione [GSH], total antioxidant capacity of plasma [FRAP], proxidasion lipids [MDA] and glutathione stransferase [GST] and also liver enzymes for instance alanin teransferase [ALT] and aspartate teransferase [AST] were estimated at 4, 8, 16 and 24 h after CCL4 injection

Results: The injection of the essential oils [at the both doses] obtained from Persian Golpar could surprisingly modulate the changes of the antioxidant/oxidative parameters as well as liver enzymes induced by CCL4 administration

Conclusion: These results indicated the protective effect of Iranian Golpar essential oils on the liver. These effects are probably due to its antioxidant capacity

Efecto de Noni C sobre el daño hepático inducido por tetracloruro de carbono en ratas / Effect of Noni C on the carbon tetrachloride-induced hepatic damage in rats

Introducción: las enfermedades hepáticas son un serio problema de salud. El estudio de agentes de origen natural que disminuyan el daño hepático inducido por sustancias químicas ha despertado un interés especial. Objetivo: evaluar el efecto del Noni C sobre el daño hepático inducido por tetracloruro de carbono, en modelo experimental desarrollado en ratas Wistar machos. Métodos: se realizó estudio experimental y se usó como control positivo el tetracloruro de carbono a dosis de 0,3 mL/kg de peso, intraperitoneal, durante 3 días; y como control negativo solución salina. Se utilizaron 4 dosis (85, 130, 170 y 215 mg/kg de peso) de Noni C durante 6 días, postratamiento con tetracloruro de carbono. Se determinaron niveles de transaminasa glutámico pirúvica y glutámico oxalacética; también lesión hepática como tumefacción celular, hepatitis reactiva, esteatosis y necrosis. Resultados: se obtuvo reducción significativa de las transaminasas glutámico pirúvica y glutámico oxalacética a las dosis de 85 y 170 mg/kg de Noni C, y ausencia de necrosis y esteatosis en los grupos tratados con las dosis de 170 y 215 mg/kg de peso. Conclusiones: en los grupos tratados con Noni C disminuyó el daño hepático inducido por el tetracloruro de carbono

Introduction: liver diseases are a serious health problem. The study of natural agents that can reduce the chemical substance-induced hepatic damage has aroused a particular interest. Objective: to evaluate the effect of Noni C on the carbon tetrachloride-induced hepatic damage in an experimental model developed in male Wistar rats. Methods: An experimental study was conducted in which the positive control was carbon tetrachloride at a dose of 0.3 mL/kg of weight, intraperitoneally administered for 3 days, and the negative control was saline solution. Four doses of Noni C(85, 130, 170 and 215 mg/kg of weight) were administered for 6 days, after treatment with the carbon tetrachloride. glutamic piruvic and glutamic oxaloacetic transaminase levels were determined, as well as hepatic lesions such as cell tumors, reactive hepatitis, steatosis and necrosis. Results: glutamic piruvic and glutamic oxaloacetic transaminases levels significantly decreased at doses of 85 and 170 mg/kg of Noni C, and no necrosis or steatosis was observed in the groups treated with 170 and 215 mg/kg doses. Conclusions: the carbon tetrachloride-induced hepatic damage diminished in the groups treated with Noni C

Hepatoprotective effect of herbal drug on CCl[4] induced liver damage

Herbs have been a huge source of natural substances used to treat and prevent several illnesses; therefore it is vital to identify the probable toxicity that might take place as a consequence of using herbal combinations. This study was undertaken in rabbits to investigate the hepatoprotective effects of herbal drug in normal and CCI[4] induced hepatic damage. Herbal drug was tested in 3 different doses, each group comprising of seven rabbits of either sex followed by the administration of CCI[4] with herbal drug and saline for 45 days. Liver function tests and histopathological evaluation were carried out at the end of dosing using standards kits. The result shows that normal dose of herbal drug [0.43 ml/kg] possess hepatoprotective effects against CCI[4] induced liver damage in rabbits which may be due to the various active ingredients present in herbal drug combination. Present study also suggests that there was a significant [p<0.05] increase in serum alkaline phosphatase and gamma-GT in animals kept on high dose of herbal drug [10 ml/kg]; however studies on huge number of animals and humans are requisite before reaching to definite conclusion

Terpenoids from Juniperus procera with hepatoprotective activity

The petroleum ether fraction of Juniperus procera showed significant activity as hepatoprotective when investigated against carbon tetrachloride induced liver injury. The hepatoprotective activity was evaluated through the quantification of biochemical parameters and confirmed using histopathology analysis. Phytochemical investigation of the petroleum ether fraction utilizing different chromatographic techniques resulted in the isolation of six known diterpenoids namely: 4-epi-abietol [1], ferruginol [2], hinokiol [3], sugiol [4], Z-communic acid [5] and hinokiol-1-one 3 beta, 12-dihydroxyabieta-8,11,13-triene-1-one] [6], in addition to the sesquiterpene 8 alpha -acetoxyelemol [7]. Both physical and spectral data were used for structure determination and all isolates were evaluated for their hepatoprotective activity. Compounds 1 and 4 were the most effective in reducing the elevated liver enzymes as indication for liver protection

Bone marrow cells ameliorate liver fibrosis and express albumin after transplantation in CCl [4] -induced fibrotic liver

We investigated the effect of bone marrow-derived stem cell [BMSC] transplantation on carbon tetrachloride [CCl [4]]-induced liver fibrosis. BMSCs of green fluorescent protein [GFP] mice were transplanted into 4-week CCl [4] -treated C57BL/6 mice directly to the liver, and the mice were treated for 4 more weeks with CCl [4] [total, 8 weeks]. After sacrificing the animals, quantitative data of percentage fibrosis area and the number of cells expressing albumin was obtained. One-way analysis of variance was applied to calculate the significance of the data. GFP expressing cells clearly indicated migrated BMSCs with strong expression of albumin after 28 days post-transplantation shown by anti-albumin antibody. Double fluorescent immunohistochemistry showed reduced expression of alpha SMA on GFP-positive cells. Four weeks after BMSC transplantation, mice had significantly reduced liver fibrosis as compared with that of mice treated with CCl [4] assessed by Sirius red staining. Mice with BMSC transplantation with continuous CCl [4] injection had reduced liver fibrosis and a significantly improved expression of albumin compared with mice treated with CCl [4] alone. These findings strengthen the concept of cellular therapy in liver fibrosis

Hepatoprotective activity of capparis spinosa root bark against CC1[4] induced hepatic damage in mice

Many hepatoprotective herbal preparations have been recommended in alternative systems of medicine for the treatment of hepatic disorders. No systematic study has been done on protective efficacy of Capparis spinosa [Capparidaceae] to treat hepaticjdiseases. Protective action of C. spinosa ethanolic root bark extract was evaluated by this study in an animal model of hepatotoxicity induced by carbon tetrachloride. Healthy male mice [30-35 g body weight, 6-8 weeks old] were divided into 7 groups. Group 1 was normal control group; Group 2, the hepatotoxic group was given CCL[4]; Group 3 was administered olive oil [vehicle]; Groups 4-6 received different doses of ethanolic root bark extract [100. 200 and 400 mg/kg] with CCL[4]; Group 7 was administered overdose of extract [800 mg/kg]. The parameters studied were alanine transaminase, aspartate transaminase activities and duration of sleep. The hepatoprotective activity was also supported by histopathological studies of liver tissue. Results of the biochemical studies of blood samples of CCL[4] treated animals showed significant increase in the levels of serum enzyme activities reflecting the liver injury caused by CCL[4]. Whereas blood samples from the animals treated with ethanolic root bark extracts showed significant decrease in the levels of serum markers indicating the protection of hepatic cells. The results revealed that ethanolic root bark extract of C. spinosa could afford significant dose-dependent protection against CCL[4] induced hepatocellular injury

[ hepatoprotective effects of Dorema auchri on carbon tetrachloride induced liver damage in rats]

The liver diseases are of the most important human kind problems. The discovery of effective medicines on the diseases is the interest of specialists. A wild species of umbelliferus plants, Dorema auchri, is used as vegetable in spring season in southern regions of Iran and is thought that it has medicinal characteristics. In this study, we evaluated the hepatoprotective effects of the crude extract of D. auchri in rats treated with carbon tetrachloride [CCl4]. In an experimental study, thirty rats were divided into five equal groups. The first group served as a control and the other groups treated with CCl4 to create hepatotoxicity. Three groups of hepatotoxic rats [treaded with CCl4] were fed with 200, 400 and 500 mg/day of crude extract of D. auchri. After 45 days, the level of liver damage was measured using aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP], and concentration of total protein, albumin and bilirubin in serum. The data were analyzed using statistical ANOVA test. Intraperitoneal injection of CCl[4] increased AST, ALT and ALP activity to 117.85, 468.6, and 134.97 and decreased the concentration of total protein, albumin and bilirubin of serum to 16.8, 20.3, and 880 percent, respectively compared to that of the control group [p<0.001]. Consumption of crude extract of D. auchri caused these factors return to the normal level. Aqueous extract of D. auchri showed hepatoprotective activities against carbon tetrachloride induced liver damage in rats

Acompanhamento de um modelo de indução de cirrose em ratos mediante vídeolaparoscopia / Accompanying of a cirrhosis induction model in rat through the videolaparoscopy

Os autores apresentam um modelo de vídeolaparoscopia experimental para avaliar a hepatotoxicidade induzida pelo tetracloreto de carbono (CCl4) em ratos. Nódulos sobre a superfície hepática e aumento significativo das provas de função hepatobiliar (alanina aminotransferase, aspartato aminotransferase, fosfatase alcalina e g -glutamiltranspeptidase) foram observados nos ratos tratados com CCl4. Além disso, cirrose hepática foi diagnosticada por estudo histopatológico em todos os ratos submetidos à administração de CC1(4). Desta maneira, a vídeolaparoscopia experimental em ratos parece ser um método diagnóstico excelente que merece mais investigação para explorar as conseqüências fisiológicas da cirurgia laparoscópica.

Atenuación del efecto hepatotóxico del tetracloruro de carbono en ratas tratadas con Polypodium polypodiodes / Mitigation of carbon tetrachloride hepatotoxic effect in polypodium polypodiodes - treated rats

Se comprobó experimentalmente en ratas la utilidad del Polypodium polypodiodes en la atenuación del efecto hepatotóxico provocado por el tetracloruro de carbono, que origina un incremento del nivel de los peróxidos lipídicos y las transaminasas sanguíneas. Se logró una disminución de la transaminasa glutamicopirúvica por debajo de los niveles normales con la administración del extracto de la planta a una dosis de 300 mg/kg de peso corporal. Los peróxidos lipídicos y la transaminasa glutamicooxalacética reducen su actividad, pero no notablemente, lo cual evidencia que el daño hepático persiste a pesar de la recuperación parcial. Los resultados fueron confirmados por un estudio anatomopatológico. Se determinó la toxicidad aguda por vía oral del extracto de la planta y se observó que la DL50 se encuentra por encima de 1 g/kg, por lo que puede considerarse esta preparación como relativamente inocua en los animales de experimentación

Kupffer cell activation with BCG, Corynebacterium parvum or zymosan protects against acute liver injury induced by carbon tetrachloride in rats

Kupffer cells have been implicated in the pathogenesis of liver injury, but there is controversy about the effects of activation of these cells on the hepatotoxicity of chemicals and endotoxin. It has been shown that injection of Corynebacterium parvum in rats induces macrophage activation that protects against toxic effects of carbon tetrachloride and acetaminophen, five days after injection, and this protection is due to inhibition of microsomal oxidizing enzimes and increased production of glutathion. To verify if the protective effect occurs soon after Kupffer cell activation, with different activators, male albino rats were treated with intravenous injection of BCG (0.5 ml with 7.5 10(8) bacilli), Corynebacterium parvum (30 mg/kg) or zymosan (7.5.10(6) yeast cells). Fourty-eight hours after the injection of one of the macrophage activators, the animals and rats treated with intravenous injection of saline (controls) received carbon tetrachloride by subcutaneous route (1 ml/kg of CCl(4), 3:1 in soybean oil). Fourty-eight hours after the animals were killed after ether anesthesia and fragments of the liver were fixed, paraffin embedded and the sections stained with hematoxylin and eosin. A Weibel grid with 168 points was used to estimate the percent volume of necrosis and severe hydropic degeneration. The results showed that the volume density of necrosis and severe hydropic degeneration were significatively lesser in rats treated with the three Kupffer cells activators. The protection was greater with BCG and Corynebacterium parvum than with zymosan. These results confirm that activation of Kupffer cell with three different activators can induce protection against liver cell injury produced by carbon tetrachloride in rats soon as 48 h after injection of activators.

O estresse oxidativo na cirrose hepática induzida por tetracloreto de carbono em ratos / Oxidative stress in hepatic cirrhosis induced by carbon tetrachloride

É objetivo dos autores avaliar se ocorre maior produçäo de radicais livres no tecido hepático cirrótico. Foram usados ratos Wistar divididos em três grupos: grupo I (controle), o qual recebeu óleo mineral; grupo II (cirrose), no qual foi induzida cirrose com tetracloreto de carbono (Ccl4)l e grupo III (Ccl4), o qual recebeu dose única de tetracloreto de carbono. A produçäo de radicais livres no tecido hepático cirrótico foi avaliada pela lipoperoxidaçäo através dos métodos de substâncias reativas ao ácido tiobarbitúrico (TBARS) e quimiluminescência iniciada por hidroperóxido de tert-butil (CL). O tecido hepático foi submetido a avaliaçäo histológica para evidenciar a presença de cirrose. Demonstrou-se maior lipoperoxidaçao no grupo II quando comparado com os grupos I e III, com diferença estatística significativa (p £ 0,05). Todos os animais tratados com Ccl4 apresentaram alteraçöes compatíveis com cirrose hepática. Observando os resultados deste estudo, podemos concluir que ocorre maior atividade metabólica de radicais livres no tecido hepático cirrótico, criando novas perspectivas no desenvolvimento de substâncias que visem diminuir o efeito deletério deste tipo de afecçäo sobre o fígado.

Rapeseed diet and hepatocyte hypertrophy: an experimental morphometric study

En un estudio previo se sugirió que la dieta suplementada con semilla de nabo evita el desarrollo de cirrosis experimental en la rata. En el presente trabajo se demostró por morfometría que la semilla de nabo produce hipertrofia de los hepatocitos. Este crecimiento, a juzgar por los hallazgos con microscopía electrónica, dependió fundamentalmente de la superficie citoplásmica, y en menor grado, del núcleo del hepatocito. La combinación de semilla de nabo con tetracloruro de carbono (CC14) produjo igualmente hipertrofia; sin embargo, aquélla no modificó el cuadro histológico de cirrosis inducida por CC14. El hecho de que la hipertrofia provocada por la semilla de nabo sea básicamente a expensas de organelos membranosos sustenta la idea de que algún ingrediente de ésta modifica la actividad de síntesis o degradación proteínica del hepatocito.

Lesiones hepáticas por drogas: presentación de 26 casos / Hepatic lesions induced by drugs: report of 26 cases

Se revisaron 2671 biopsias hepáticas entre los años 1972 y 1985 en el Hospital A. Posadas. Hubo 26 pacientes con daño hepático producido por drogas, habiéndose incluido aquellos enfermos con los siguientes criterios: contacto con un fármaco capaz de producir efecto hepatotóxico; cuadro clínico, biológico e histológico compatible con la droga examinada; remisión completa del cuadro al interrumpir la droga; ausencia de otros tóxicos hepáticos. Catorce pacientes mostraron colestasis intrahepática inducida por estrógenos; 5 tuvieron lesiones hepatitis-like debido a: alfametildopa (3), ketoconazol (1) e indometacina (1). Dos presentaron cambios inflamatorios y cambios grasos por tetracloruro de carbono mientras que la fenibutazona produjo una granulomatosis hepática y una hepatitis colestática. Los últimos tres casos fueron lesiones colestáticas después de la administración de clorpromazina allopurinol y penicilina respectivamente. La evolución en 24 pacientes fue excelente después que se retiró la droga. Dos pacientes murieron por complicaciones quirúrgicas ya que fueron operados con el diagnóstico erróneo de colestasis extrahepática

The effect of verapamil on toxic liver cell death induced by carbon tetrachloride

Os autores estudaram os efeitos do verapamil sobre a necrose hepática induzida pelo tetracloreto de carbono no camundongo. O tratamento de camundongos com verapamil, antes e após o C Cl4, protege o hepatócito da necrose: a necrose centrolobular foi menor nos camundongos tratados com verapamil. Um discreto efeito protetor foi observado quando os animais receberam uma só dose de verapamil, três horas antes ou três horas depois do C Cl4. É possível que o efeito protetor seja maior quando os níveis plasmáticos da droga säo mantidos por período maiores após a injeçäo de C Cl4