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1.
Acta Physiologica Sinica ; (6): 901-908, 2021.
Article in Chinese | WPRIM | ID: wpr-921294

ABSTRACT

The aim of the present study was to investigate the effects of dexmedetomidine (DEX) on acute liver injury induced by lipopolysaccharide (LPS)/D-galactosamine (D-Gal) and the underlying mechanism. Male BALB/c mice were intraperitoneally injected with LPS/D-Gal to induce acute liver injury model, and pretreated with DEX or in combination with the autophagy inhibitor, 3-methyladenine (3-MA) 30 min before injection. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, as well as myeloperoxidase (MPO) activity in liver tissue were determined with the corresponding kits. Serum tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels were determined by ELISA. The protein expression levels of LC3-II and P62 in liver tissue were determined by Western blot. Liver histopathological changes were detected by HE staining. The results showed that, compared with control group, LPS/D-Gal enhanced ALT and AST activity, increased TNF-α and IL-6 levels, as well as MPO activity, up-regulated LC3-II and P62 protein expression levels, and significantly induced pathological damage in liver tissue. DEX reversed the above changes in the LPS/D-Gal group, whereas these protective effects of DEX were blocked by 3-MA. The above results suggest that DEX alleviates LPS/D-Gal-induced acute liver injury, which may be associated with the up-regulation of LC3-II protein expression and the activation of autophagy.


Subject(s)
Alanine Transaminase , Animals , Chemical and Drug Induced Liver Injury/drug therapy , Dexmedetomidine/pharmacology , Galactosamine/toxicity , Interleukin-6/blood , Lipopolysaccharides/toxicity , Liver , Male , Mice , Mice, Inbred BALB C , Microtubule-Associated Proteins/metabolism , Tumor Necrosis Factor-alpha/blood , Up-Regulation
2.
Int. j. morphol ; 38(5): 1444-1454, oct. 2020. tab, graf
Article in English | LILACS | ID: biblio-1134461

ABSTRACT

SUMMARY: Over dose or long-term clinical use of therapeutic doses of acetaminophen (APAP) causes hepatotoxicity. Various strategies attempted to ameliorate APAP-hepatotoxicity have been found to be unsuitable for clinical practice. This study was aimed to illustrate the histopathological changes induced by therapeutic dose of APAP and investigate the hepatoprotective role of oral co-administration of selenium/ Tribulus terrestris (TT) extract concurrently against hepatotoxicity induced by APAP in rats. Fifty-four healthy male albino Wistar rats were randomized into nine groups (G1-G9) of six rats each, and administered with APAP and TT orally for 30 days as follows: Control (2ml normal saline), APAP (470 mg/kg), APAP (470 mg/kg) + selenium (2 mg/kg), APAP (470 mg/kg) + TT (98 mg/kg), APAP (470 mg/kg) + selenium (2mg/kg) + TT (98 mg/kg), APAP (470 mg/kg) + silymarin (200 mg/kg), selenium (2 mg/ kg), TT (98 mg/kg) and silymarin (200 mg/kg) groups. The results demonstrated that exposure of rats to therapeutic dose of APAP for 30 days caused significant histopathological changes parallel to elevated blood chemistry parameters. Co-administration of selenium/TT extract showed significantly reduced histopathological lesions and, restored or decreased levels of the examined blood chemistry parameters. Liver histology in selenium/TT extract showed normal hepatic architecture with mild changes and silymarin treated rats showed no histopathological changes. Histochemically PAS staining, showed that APAP-induced hepatotoxicity was characterized by hepatocytes glycogen depletion. Selenium/TT co-supplementation plays a potential role in preventing APAP-induced glycogen depletion by increasing detoxification and scavenging the reactive metabolites. Selenium/TT extract oral co-administration possesses a significant hepatoprotective property and mitigates APAP-induced hepatotoxicity by enhancing its antioxidant role and improving tissue integrity. Selenium/TT supplementation could represent an effective treatment against APAP-induced hepatotoxicity. Further studies are needed to elucidate the exact mechanism underlying the protective role of TT extract.


RESUMEN: La dosis excesiva o el uso clínico a largo plazo de dosis terapéuticas de acetaminofeno (APAP) causa hepatotoxicidad. Se ha descubierto que varias estrategias que intentaron mejorar la hepatotoxicidad por APAP no son adecuadas para la práctica clínica. Este estudio tuvo como objetivo ilustrar los cambios histopatológicos inducidos por la dosis terapéutica de APAP e investigar el papel hepatoprotector de la administración conjunta de extracto de selenio / Tribulus terrestris (TT) simultá- neamente contra la hepatotoxicidad inducida por APAP en ratas. Cincuenta y cuatro ratas Wistar albino machos sanas se aleatorizaron en nueve grupos (G1 - G9) de seis ratas cada una, y se administraron con APAP y TT por vía oral durante 30 días de la siguiente manera: Control (2 ml de solución salina normal), APAP (470 mg / kg), APAP (470 mg / kg) + selenio (2 mg / kg), APAP (470 mg / kg) + TT (98 mg / kg), APAP (470 mg / kg) + selenio (2 mg / kg) + TT (98 mg / kg), APAP (470 mg / kg) + silimarina (200 mg / kg), selenio (2 mg / kg), TT (98 mg / kg) y silimarina (200 mg / kg). Los resultados demostraron que la exposición de las ratas a la dosis terapéutica de APAP durante 30 días causó cambios histopatológicos significativos paralelos a parámetros elevados de química sanguínea. La administración conjunta de extracto de selenio / TT mostró lesiones histopatológicas significativamente reducidas y niveles restaurados o disminuidos de los parámetros de química sanguínea. La histología hepática en el extracto de selenio / TT mostró una arquitectura hepática normal con cambios leves y las ratas tratadas con silimarina no mostraron cambios histopatológicos. La tinción histoquímica de PAS mostró que la hepatotoxicidad inducida por APAP se caracterizó por la pérdida de glucógeno de los hepatocitos. La suplementación con selenio / TT juega un papel potencial en la prevención de la pérdida de glucógeno inducido por APAP al aumentar la desintoxicación y eliminar los metabolitos reactivos. La administración conjunta de extracto de selenio / TT posee una propiedad hepatoprotectora significativa y mitiga la hepatotoxicidad inducida por APAP al mejorar su papel antioxidante y la integridad del tejido. La suplementación con selenio / TT podría representar un tratamiento efectivo contra la hepatotoxicidad inducida por APAP. Se necesitan más estudios para dilucidar el mecanismo exacto que subyace a la función protectora del extracto TT.


Subject(s)
Animals , Male , Rats , Selenium/administration & dosage , Plant Extracts/administration & dosage , Tribulus/chemistry , Chemical and Drug Induced Liver Injury/drug therapy , Acetaminophen/toxicity , Administration, Oral , Rats, Wistar , Glycogen , Liver/drug effects
3.
Int. j. morphol ; 38(3): 558-564, June 2020. tab, graf
Article in English | LILACS | ID: biblio-1098287

ABSTRACT

Chronic hepatotoxicity is a debilitating and frequently life-threatening disease resulting in progressive liver failure. The toxic chemical, thioacetamide (TAA) is used to evaluate hepatoprotective agents, and the polyphenolic compound, resveratrol was proposed as a novel treatment for diseases with hyperactivation of the mammalian target of rapamycin (mTOR) cell signaling pathway. This analysis sought to investigate the potential protective effect of resveratrol against liver injury induced by TAA via the inhibition of hepatic mTOR. Model group rats received several injections of TAA (200 mg/kg; twice a week for 8 weeks) before being sacrificed at week 10 and the protective group was pretreated with resveratrol (20 mg/kg) daily for two weeks prior to TAA injections and continued receiving both agents until the end of the experiment. Harvested liver tissues were examined using light microscopy and liver homogenates were assayed for biomarkers of inflammation and assessed the levels of mTOR protein in all animal groups. In addition, blood samples were assayed for biomarkers of liver injury enzyme. TAA substantially damaged the hepatic tissue of the model group such as infiltration of inflammatory cells, vacuolated cytoplasm, dark pyknotic nuclei, and dilated congested blood vessel that were effectively protected by resveratrol. Resveratrol also significantly (p<0.05) inhibited TAA-induced mTOR, high sensitivity c-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in harvested liver homogenates and blood samples. Thus, we conclude that resveratrol effectively protects against TAA-induced hepatotoxicity in rats, possibly due to the inhibition of mTOR and inflammation.


La hepatotoxicidad crónica es una enfermedad debilitante y potencialmente mortal que produce insuficiencia hepática progresiva. La toxicidad del químico de la tioacetamida (TAA) se utiliza para evaluar los agentes hepatoprotectores y el compuesto polifenólico, resveratrol, se propuso como un nuevo tratamiento para enfermedades con hiperactivación de la vía de señalización celular mTOR (mammalian Target of Rapamycin). Aquí buscamos investigar el posible efecto protector del resveratrol contra la lesión hepática inducida por TAA a través de la inhibición de la vía de señalización mTOR en hepatocitos. Las ratas del grupo modelo recibieron varias inyecciones de TAA (200 mg / kg; dos veces por semana durante 8 semanas) antes de ser sacrificadas en la semana 10 y el grupo protector se trató previamente con resveratrol (20 mg / kg) diariamente durante dos semanas antes de las inyecciones de TAA y continuó recibiendo ambos agentes hasta el final del experimento. Se examinaron los tejidos hepáticos recolectados usando microscopía óptica y se analizaron los homogeneizados hepáticos para detectar biomarcadores de inflamación y se evaluaron los niveles de proteína mTOR en todos los grupos de animales. Además, se analizaron muestras de sangre para detectar biomarcadores de la enzima de lesión hepática. TAA dañó sustancialmente el tejido hepático del grupo modelo, con infiltración de células inflamatorias, citoplasma vacuolado, núcleos picnóticos oscuros y vasos sanguíneos congestionados dilatados que estaban efectivamente protegidos por el resveratrol. El resveratrol también inhibió significativamente (p <0.05) mTOR, proteína C-reactiva (hs-CRP), factor de necrosis tumoral alfa (TNF-α), interleucina-6 (IL-6), alanina aminotransferasa (ALT ) y aspartato aminotransferasa (AST) en las muestras de sangre y de hígados recolectados. En conclusión, el resveratrol protege eficazmente contra la hepatotoxicidad inducida por TAA en ratas, posiblemente debido a la inhibición de mTOR y de la inflamación.


Subject(s)
Animals , Male , Mice , Thioacetamide/toxicity , Chemical and Drug Induced Liver Injury/drug therapy , TOR Serine-Threonine Kinases/antagonists & inhibitors , Resveratrol/administration & dosage , Aspartate Aminotransferases/analysis , C-Reactive Protein/analysis , Tumor Necrosis Factor-alpha/analysis , Alanine Transaminase/analysis , Disease Models, Animal
4.
Int. j. morphol ; 36(2): 661-669, jun. 2018. graf
Article in English | LILACS | ID: biblio-954169

ABSTRACT

Thioacetamide (TAA) is one of the common fungicidal agents that induce liver injury varying from inflammation, necrosis, and fibrosis to cirrhosis. Many recent studies reported the beneficial effect of probiotics and silymarin on hepatotoxicity regardless the causative agents. Therefore, the present study aimed to evaluate the ameliorative role of probiotics and/or silymarin on TAA induced hepatotoxicity in rats via histological, and immunohistochemical methods. Twenty five male albino rats were used for this experiment and were divided into five groups (n=5 rats/group); group I acts as negative control, group II was orally administrated distilled water for six weeks, then injected with TAA (200 mg/kg b.wt./ 5 ml physiological saline/ I.P.) twice a week for another six weeks, group III was treated with probiotics at a dose of 135 mg/ kg b.wt. orally in drinking water daily for six weeks, then injected with TAA (dosage of group II), twice weekly for another six weeks, group IV was treated with silymarin at a dose of 200 mg/ kg b.wt orally 4 times per week for six weeks, then injected with TAA (dosage of group II), twice weekly for another six weeks and group V was treated with combination of both probiotics and silymarin, at the same dosage in groups III and IV respectively then injected with TAA (dosage of group II), twice weekly for another six weeks. Histologically, TAA induced hepatocytes degeneration, inflammatory cells infiltration, and pseudolobular parenchyma as well as, high apoptosis and low proliferation rates that were proved by immunohistochemical staining for caspase 3 and ki-67 respectively. Probiotics and/or silymarin improved the histological feature of hepatocytes, reduced apoptosis and stimulated proliferation. Based on these results, we concluded that the use of probiotics and silymarin combination ameliorates the hepatotoxic effect of TAA in rats more than the use of probiotics or silymarin alone.


La tioacetamida (TAA) es uno de los agentes fungicidas más comunes que inducen lesiones hepáticas que varían desde inflamación, necrosis y fibrosis hasta cirrosis. Muchos estudios recientes informaron el efecto beneficioso de los probióticos y la silimarina sobre la hepatotoxicidad independientemente de los agentes causantes. Por lo tanto, el presente estudio tuvo como objetivo evaluar el papel paliativo de los probióticos y / o silimarina en la hepatotoxicidad inducida por TAA en ratas a través de métodos histológicos e inmunohistoquímicos. Para este experimento se usaron veinticinco ratas albinas y se dividieron en cinco grupos (n = 5 ratas / grupo); el grupo I se usó como control negativo; en el grupo II se administró por vía oral agua destilada durante seis semanas y luego se inyectó TAA (200 mg / kg b.wt./ 5 ml solución salina fisiológica / IP) dos veces por semana durante otras seis semanas; el grupo III se trató con probióticos, dosis diaria de 135 mg / kg b.wt. por vía oral en agua potable, durante seis semanas y luego fue inyectado con TAA (dosis del grupo II), dos veces por semana durante otras seis semanas; el grupo IV se trató con silimarina, con una dosis de 200 mg / kg b.wt por vía oral 4 veces por semana durante seis semanas, luego se inyectó TAA (dosificación del grupo II), dos veces por semana durante otras seis semanas; y el grupo V, se trató con una combinación de ambos probióticos y silimarina con la misma dosis que en los grupos III y IV, respectivamente, luego fueron inyectados con TAA (dosificación del grupo II), dos veces por semana durante otras seis semanas. Histológicamente, la TAA indujo la degeneración de los hepatocitos, la infiltración de células inflamatorias y el parénquima pseudolobular, así como también una apoptosis alta y tasas de proliferación bajas que se probaron mediante tinción inmunohistoquímica para caspasa 3 y ki-67, respectivamente. Los probióticos y / o la silimarina mejoraron la característica histológica de los hepatocitos, redujeron la apoptosis y estimularon la proliferación. En base a estos resultados, concluimos que el uso de la combinación de probióticos y silimarina mejora el efecto hepatotóxico del TAA en ratas más que el uso de probióticos o silimarina individualmente.


Subject(s)
Animals , Male , Rats , Silymarin/administration & dosage , Thioacetamide/toxicity , Probiotics/administration & dosage , Chemical and Drug Induced Liver Injury/drug therapy , Immunohistochemistry , Chemical and Drug Induced Liver Injury/pathology , Liver/drug effects
5.
Acta cir. bras ; 32(6): 407-417, June 2017. tab, graf
Article in English | LILACS | ID: biblio-886210

ABSTRACT

Abstract Purpose: To investigate the hepatoprotective and antioxidant effeicacies of Silybum marianum's (silymarin, S) on University of Wisconsin (UW) and histidinetryptophan-ketoglutarate (HTK) preservation solutions. Methods: Thirty two Wistar albino adult male rats were used. Group 1: UW group, Group 2: UW + Silymarin group(S), Group 3: HTK group, Group 4: HTK + silymarin group (S), respectively. Silymarin was enforced intraperitoneally before the surgery. Biopsies were enforced in 0, 6 and 12.hours to investigate. Results: Biochemical parameters examined in alanine aminotransferase (ALT), furthermore superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) in rats were also evaluated. Detected histopathological changings were substantially declining in the groups that received silymarin, cellular damage was decreased significantly in HTK + Silymarin group, according to other groups. It has been identified as the most effective group was HTK + silymarin group in evaluation of ALT, electron microscopic results, also decreased MDA and elevated in SOD, and CAT activity. Caspase 3 analysis showed a substantial lower apoptosis ratio in the silymarin groups than in the non-performed groups (p<0.05). Conclusion: Histidinetryptophan-ketoglutarate+silymarin group provides better hepatoprotection than other groups, by decreasing the hepatic pathologic damage, delayed changes that arise under cold ischemic terms.


Subject(s)
Animals , Male , Rats , Silymarin/therapeutic use , Organ Preservation Solutions , Protective Agents/therapeutic use , Chemical and Drug Induced Liver Injury/drug therapy , Antioxidants/therapeutic use , Potassium Chloride , Procaine , Raffinose , Immunohistochemistry , Adenosine , Allopurinol , Rats, Wistar , Disease Models, Animal , Glucose , Glutathione , Insulin , Mannitol
6.
Acta cir. bras ; 30(11): 778-784, Nov. 2015. tab, graf
Article in English | LILACS | ID: lil-767597

ABSTRACT

PURPOSE: To investigate the possible protective effect of rutin on methotrexate induced hepatotoxicity in rats. METHODS: Twenty-two rats were divided into three experimental groups; Control-saline, Mtx, Mtx+Rutin. Hepatic tissue was taken for histological assessment and biochemical assays. Oxidative stress parameters malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were investigated. Liver markers aspartate aminotransferase (AST), alanine aminotransferase (ALT) were analyzed in serum. RESULTS: Mtx+Rutin group showed lower histological injury compared to Mtx group, MDA and ALT levels were increased, while SOD and GSH-Px were decreased in Mtx group compared with Control-saline group. MDA and ALT levels were increased, while SOD and GSH-Px were decreased in Mtx group, compared with Mtx +Rutin group. Serum AST levels were similar among the groups. CONCLUSION: Rutin may be a potential adjuvant drug to reduce the hepatic side effects observed during Mtx therapy for various clinical conditions.


Subject(s)
Animals , Female , Chemical and Drug Induced Liver Injury/drug therapy , Immunosuppressive Agents/toxicity , Methotrexate/toxicity , Rutin/therapeutic use , Alanine Transaminase/blood , Antioxidants/pharmacology , Antioxidants/therapeutic use , Aspartate Aminotransferases/blood , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury/prevention & control , Glutathione Peroxidase/analysis , Liver/drug effects , Liver/pathology , Malondialdehyde/analysis , Oxidative Stress/drug effects , Rats, Wistar , Reproducibility of Results , Rutin/pharmacology , Superoxide Dismutase/analysis
7.
Biol. Res ; 48: 1-9, 2015. ilus, graf, tab
Article in English | LILACS | ID: biblio-950783

ABSTRACT

BACKGROUND: To evaluate the hepatoprotective potential and invitro cytotoxicity studies of whole plant methanol extract of Rumex vesicarius L. Methanol extract at a dose of 100 mg/kg bw and 200 mg/kg bw were assessed for its hepatoprotective potential against CCl4-induced hepatotoxicity by monitoring activity levels of SGOT (Serum glutamic oxaloacetic transaminase), SGPT (Serum glutamic pyruvic transaminase), ALP (Alkaline phosphatase), TP (Total protein), TB (Total bilirubin) and SOD (Superoxide dismutase), CAT (Catalase), MDA (Malondialdehyde). The cytotoxicity of the same extract on HepG2 cell lines were also assessed using MTT assay method at the concentration of 62.5, 125, 250, 500 µg/ml. RESULTS: Pretreatment of animals with whole plant methanol extracts of Rumex vesicarius L. significantly reduced the liver damage and the symptoms of liver injury by restoration of architecture of liver. The biochemical parameters in serum also improved in treated groups compared to the control and standard (silymarin) groups. Histopathological investigation further corroborated these biochemical observations. The cytotoxicity results indicated that the plant extract which were inhibitory to the proliferation of HepG2 cell line with IC50 value of 563.33 ± 0.8 Mg/ml were not cytotoxic and appears to be safe. CONCLUSIONS: Rumex vesicarius L. whole plant methanol extract exhibit hepatoprotective activity. However the cytotoxicity in HepG2 is inexplicable and warrants further study.


Subject(s)
Humans , Animals , Male , Rats , Plant Extracts/pharmacology , Cytotoxins/pharmacology , Rumex/chemistry , Cell Proliferation/drug effects , Chemical and Drug Induced Liver Injury/drug therapy , Phytotherapy/methods , Aspartate Aminotransferases/metabolism , Silymarin/pharmacology , Superoxide Dismutase/metabolism , Tetrazolium Salts , Bilirubin/metabolism , Carbon Tetrachloride , Catalase/metabolism , Anticarcinogenic Agents/pharmacology , Rats, Wistar , Alanine Transaminase/metabolism , Methanol , Drinking/drug effects , Eating/drug effects , Alkaline Phosphatase/metabolism , Hep G2 Cells , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Formazans , Liver/drug effects , Liver/metabolism , Malondialdehyde/metabolism , Antioxidants/metabolism , Antioxidants/pharmacology
8.
Biol. Res ; 48: 1-10, 2015. graf, tab
Article in English | LILACS | ID: biblio-950794

ABSTRACT

BACKGROUND: Carbon tetrachloride (CCl4) induces hepatotoxicity in animal models, including the increased blood flow and cytokine accumulation that are characteristic of tissue inflammation. The present study investigates the hepato-protective effect of rutin on CCl4-induced hepatotoxicity in rats. RESULTS: Forty male Wistar rats were divided into four groups. Group I (control group) received 1 mL/kg of dimethyl sulfoxide intragastrically and 3 mL/kg olive oil intraperitoneally twice a week for 4 weeks. Group II received 70 mg/ kg rutin intragastrically. Groups III and IV received CCl4 (3 mL/kg, 30 % in olive oil) intraperitoneally twice a week for 4 weeks. Group IV received 70 mg/kg rutin intragastrically after 48 h of CCl4 treatment. Liver enzyme levels were determined in all studied groups. Expression of the following genes were monitored with real-time PCR: interleukin-6 (IL-6), dual-specificity protein kinase 5 (MEK5), Fas-associated death domain protein (FADD), epidermal growth factor (EGF), signal transducer and activator of transcription 3 (STAT3), Janus kinase (JAK), B-cell lymphoma 2 (Bcl2) and B-cell lymphoma-extra-large (Bcl-XL). The CCl4 groups showed significant increases in biochemical markers of hepatotoxicity and up-regulation of expression levels of IL-6, Bcl-XL, MEK5, FADD, EGF, STAT3 and JAK compared with the control group. However, CCl4 administration resulted in significant down-regulation of Bcl2 expression compared with the control group. Interestingly, rutin supplementation completely reversed the biochemical markers of hepatotoxicity and the gene expression alterations induced by CCl4. CONCLUSION: CCl4 administration causes alteration in expression of IL-6/STAT3 pathway genes, resulting in hepatotoxicity. Rutin protects against CCl4-induced hepatotoxicity by reversing these expression changes.


Subject(s)
Animals , Male , Rats , Rutin/pharmacology , Signal Transduction/drug effects , Interleukin-6/metabolism , STAT3 Transcription Factor/metabolism , Chemical and Drug Induced Liver Injury/drug therapy , Aspartate Aminotransferases/blood , Carbon Tetrachloride , Biomarkers , Gene Expression/drug effects , Rats, Wistar , Proto-Oncogene Proteins c-bcl-2/metabolism , Protective Agents/pharmacology , MAP Kinase Kinase 5/metabolism , Alanine Transaminase/blood , Epidermal Growth Factor/metabolism , bcl-X Protein/metabolism , Janus Kinases/metabolism , Fas-Associated Death Domain Protein/metabolism , Real-Time Polymerase Chain Reaction , Liver/drug effects
9.
Acta cir. bras ; 29(12): 776-780, 12/2014. tab
Article in English | LILACS | ID: lil-731026

ABSTRACT

PURPOSE: To investigate the copaiba oil on the hepatic damage induced by acetaminophen, comparing against corn oil. METHODS: Fifty four rats were distributed into nine study groups (N=6): control group, that didn't receive the acetaminophen; Acetaminophen Group, that only received the acetaminophen; Prophylactic Copaiba Group 1, that received copaiba oil two hours before the acetaminophen; Prophylactic Copaiba Group 7, that received copaiba oil seven days, once by day, before the acetaminophen; Therapy Copaiba Group, that received the copaiba oil two hours after the acetaminophen, the corn's groups were similar than copaiba oil groups; and N-Acetyl-Cysteine Group, that received the N-Acetyl-Cysteine two hours after the acetaminophen. Euthanasia was performed after 24 hours. The serum levels transaminases, bilirubin and canalicular enzymes were analyzed. RESULTS: The prophylactic copaiba group 7, therapy copaiba group and N-Acetyl-Cysteine Group showed amounts of AST and ALT similar to the control group; and the prophylactic copaiba group 1 and corn's groups showed similar levels to the acetaminophen group. There was no significant difference between the groups regarding the amount of alkaline phosphatase and ɤ GT (p>0.05). The therapy copaiba group showed the highest levels of total bilirubin and was statistically different from the other groups (p<0.01). CONCLUSIONS: Copaiba oil administered prophylactically for seven days and therapeutically 2 hours after the acetaminophen acute intoxication offered a potential hepato protection against paracetamol-induced hepatic damage, normalizing the biochemical parameters similarly to N-Acetyl-Cysteine, and the treatment with corn oil shows no effect on the liver damage. .


Subject(s)
Animals , Male , Acetaminophen/toxicity , Chemical and Drug Induced Liver Injury/drug therapy , Fabaceae/chemistry , Plant Oils/therapeutic use , Acetylcysteine/therapeutic use , Alanine Transaminase/blood , Alkaline Phosphatase/blood , Aspartate Aminotransferases/blood , Bilirubin/blood , Corn Oil/therapeutic use , Disease Models, Animal , Chemical and Drug Induced Liver Injury/metabolism , Plant Oils/administration & dosage , Random Allocation , Rats, Wistar , Treatment Outcome , gamma-Glutamyltransferase/blood
10.
Article in Spanish | LILACS | ID: lil-795825

ABSTRACT

A preclinical pharmacological study was conducted to evaluate the hepatoprotective effect of Mentha piperita L. against paracetamol induced toxicity. Adult male NMRI mice who were administered orally soft plant extracts in doses of 200mg/kg and 400mg/kg, three consecutive days prior to the induction of hepatotoxicity were used. Clinical signs of toxicity, hepatic biochemical parameters and morphological analysis of the liver was evaluated. The biochemical parameters analyzed showed significant differences, but none of the two groups showed a similar untreated control group behavior. No macroscopic changes in the liver were confirmed. Microscopically, the study groups with Mentha piperita L. showed mild to moderate damage with significant differences from the untreated control group. The evaluation of hepatoprotective potential on the M. piperita L. extract at doses studied did not behave as hepatoprotective agent...


Se realizó un estudio farmacológico preclínico para evaluar el efecto hepatoprotector de Mentha piperita L. frente a la toxicidad inducida por el paracetamol. Se emplearon ratones adultos machos NMRI a los que se administró por vía oral extractos blandos de la planta a dosis de 200 mg/kg y 400 mg/kg, tres días consecutivos previos a la inducción de la hepatotoxicidad. Se evaluaron los signos clínicos de toxicidad, parámetros bioquímicos hepáticos y el análisis morfológico del hígado. Los parámetros bioquímicos analizados mostraron diferencias altamente significativas, pero ninguno de los dos grupos presentaron un comportamiento similar al grupo control no tratado. No se confirmaron alteraciones macroscópicas del hígado. A nivel Microscópico, los grupos en estudio con Mentha piperita L. presentaron daños de leves a moderados con diferencias significativas respecto al grupo control no tratado. Se puede afirmar que según la evaluación del potencial hepatoprotector del extracto de M. piperita L. a las dosis estudiadas no se comportó como agente hepatoprotector...


Subject(s)
Male , Animals , Mice , Acetaminophen/toxicity , Chemical and Drug Induced Liver Injury/drug therapy , Plant Extracts/administration & dosage , Liver/pathology , Mentha piperita/chemistry , Administration, Oral , Analgesics, Non-Narcotic/toxicity , Chemical and Drug Induced Liver Injury/pathology
11.
Indian J Biochem Biophys ; 2014 Oct; 51(5): 372-377
Article in English | IMSEAR | ID: sea-154266

ABSTRACT

The phytochemicals present in the grapes are responsible for nutraceutical and health benfits due to their antioxidant properties. These phytochemicals, however, vary greatly among different cultivars. In this study, we evaluated the antioxidant potential and protective role of four different Indian grape (Vitis vinifera) cultivars extracts, namely Flame seedless (Black grapes), Kishmish chorni (Black with reddish brown), Red globe (Red) and Thompson seedless mutant (Sonaka, Green) against the Fenton-like reagent (200 mmole H2O2, 2 mmole ascorbate, 25 mmole FeSO4)-induced liver damage. Non-enzymatic antioxidants, such as glutathione (GSH) levels and activities of antioxidant enzymes, such as glutathione S-transferase (GST) and superoxide dismutase (SOD), as well as total antioxidant capacity (TAC) were highest in the grape seed, followed by skin and pulp. Among edible parts of different cultivars, skin of Flame seedless (Black) cultivar showed highest antioxidant potential, while the Thompson seedless the least potential. These antioxidants were found to be significantly (P<0.01) correlated with the levels of total phenol, flavonoids and ascorbic acid. Fenton-like reagent treatment significantly (P<0.001) decreased GSH content by 39.1% and activities of catalase (CAT) by 43.2% and glutathione reductase (GR) by 60%, while increasing thiobarbituric acid reactive substances (TBARS) and nitric oxide levels by 2.13-fold and 0.64-fold, respectively and GST activity by 0.81-fold. Pre-treatment with grape seed extracts showed the best hepatoprotective action against Fenton-like reagent-induced damage, followed by the extracts of skin and pulp of any cultivar. Thus, our study showed the significant amounts of antioxidants were in grape seed, followed by its skin and pulp, which varied among the cultivars and was associated with the protective action of grape extracts against Fenton-like reagent-induced liver damage ex-vivo.


Subject(s)
Animals , Antioxidants/administration & dosage , Dose-Response Relationship, Drug , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/metabolism , Fruit/chemistry , Goats , Hydrogen Peroxide , Iron , Phytotherapy/methods , Plant Extracts/administration & dosage , Plant Structures/chemistry , Reactive Oxygen Species/metabolism , Treatment Outcome , Vitis/chemistry
12.
Indian J Exp Biol ; 2014 Mar; 52(3): 207-214
Article in English | IMSEAR | ID: sea-150350

ABSTRACT

The alcoholic extract of stem of E. pursaetha (PSE, 30, 100, 300 mg/kg body weight, po for 7 days) showed hepatoprotective activity against CCl4 (2 mL/kg body weight, ip)-induced hepatotoxicity. The extract exhibited a significant dose-dependent hepatoprotective effect comparable to standard drug silymarin, by preventing increase in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, and total bilirubin, lactate dehydrogenase; by lowering hepatic levels of malonaldehyde, nitrate-nitrite, myeloperoxidase activity; enhancing activities of antioxidant enzymes, superoxide dismutase, catalase and increasing reduced glutathione levels in liver, which suggests the antioxidant property of PSE. Histopathological studies also supported the above biochemical parameters. The results suggested that alcoholic extract of E. pursaetha possesses significant hepatoprotective activity in CCl4-induced acute hepatotoxicity in rats and this is likely to be mediated through its antioxidant activities.


Subject(s)
Animals , Antioxidants/metabolism , Carbon Tetrachloride/toxicity , Catalase/metabolism , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/pathology , Fabaceae/chemistry , Glutathione/metabolism , Lipid Peroxidation/drug effects , Liver/drug effects , Liver/pathology , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Rats , Superoxide Dismutase/metabolism
13.
Article in English | WPRIM | ID: wpr-106803

ABSTRACT

Methimazole and propylthiouracil have been used in the management of hyperthyroidism for more than half a century. However, hepatotoxicity is one of the most deleterious side effects associated with these medications. The mechanism(s) of hepatic injury induced by antithyroid agents is not fully recognized yet. Furthermore, there are no specific tools for predicting the occurrence of hepatotoxicity induced by these drugs. The purpose of this article is to give an overview on possible susceptibility factors in liver injury induced by antithyroid agents. Age, gender, metabolism characteristics, alcohol consumption, underlying diseases, immunologic mechanisms, and drug interactions are involved in enhancing antithyroid drugs-induced hepatic damage. An outline on the clinically used treatments for antithyroid drugs-induced hepatotoxicity and the potential therapeutic strategies found to be effective against this complication are also discussed.


Subject(s)
Animals , Antithyroid Agents/adverse effects , Disease Models, Animal , Chemical and Drug Induced Liver Injury/drug therapy , Graves Disease/drug therapy , Humans , Hyperthyroidism/drug therapy , Protective Agents/therapeutic use , Reactive Oxygen Species/metabolism , Risk Factors
14.
Indian J Exp Biol ; 2013 Dec; 51(12): 1109-1119
Article in English | IMSEAR | ID: sea-150299

ABSTRACT

Plausible interactions between food contaminants and natural constituents in vivo and protective effect of polyphenols present in I. aquatica against carbofuran toxicity in Charles Foster rats were evaluated. Determinations based on antioxidant enzyme activities showed significant alterations in glutathione, glutathione peroxidase, superoxide dismutase and catalase in tissues (liver and brain) and plasma of pesticide treated group while polyphenolic extracts from I. aquatica (IAE) attenuated their activities when given alongwith carbofuran. IAE decreased enhanced lipid peroxidation levels in plasma and erythrocyte membrane and cholesterol levels in brain and plasma. IAE also minimized histopathological degenerative changes produced by carbofuran. While single cell gel electrophoresis showed that secondary metabolites in leafy vegetables produced a combinatorial effect with pesticide at cellular level, DNA fragmentation level in bone marrow cells showed a decline in the IAE treated rats. Food safety adversely affected by various chemical contaminants can be retained by plant polyphenols and secondary plant constituents that can be found together in bolus. Therefore, the present study gives an insight into the protective role of naturally found polyphenols against pesticide toxicity.


Subject(s)
Animals , Antioxidants/administration & dosage , Antioxidants/chemistry , Carbofuran/toxicity , Catalase/blood , Chemical and Drug Induced Liver Injury/blood , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/enzymology , Glutathione Peroxidase/blood , Ipomoea/chemistry , Lipid Peroxidation/drug effects , Liver/drug effects , Liver/enzymology , Male , Oxidative Stress/drug effects , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Polyphenols/administration & dosage , Polyphenols/chemistry , Rats , Superoxide Dismutase/blood
15.
Acta cir. bras ; 28(7): 526-530, July 2013. tab
Article in English | LILACS | ID: lil-679085

ABSTRACT

PURPOSE: To investigate the effects of copaiba oil on the hepatic damage induced by paracetamol. METHODS: Thirty six rats were distributed into six study groups (N=6): control group, that didn't receive the acetaminophen; Acetaminophen Group, that only received the acetaminophen; Prophylactic Copaiba Group 1, that received copaiba oil two hours before the acetaminophen; Prophylactic Copaiba Group 7, that received copaiba oil seven days, once by day, before the acetaminophen; Therapy Copaiba Group, that received the copaiba oil two hours afther the acetaminophen; and N-Acetyl-Cysteine Group, , that received the N-Acetyl-Cysteine two hours afther the acetaminophen. Euthanasia was performed after 24 hours. The serum levels of AST, ALT, alkaline phosphatase, GT, total bilirubin, direct bilirubin and indirect bilirubin and histological analisis were analized. RESULTS: The prophylactic copaiba group 7, therapy copaiba group and N-Acetyl-Cysteine Group showed amounts of AST and ALT similar to the control group; and the prophylactic copaiba group 1 showed similar levels to the acetaminophen group. There was no significant difference between the groups regarding the amount of alkaline phosphatase and GT (p>0.05). The therapy copaiba group showed the highest levels of bilirubin and was statistically different from the other groups (p<0.01) and this increased the costs of direct bilirubin. Regarding histopathology, the oil of copaiba administered prophylactic or therapeutic form for 7 days could decrease the amount of necrosis and inflammatory infiltrate. CONCLUSION: Copaiba oil administered prophylactically for seven days, and therapeutic could reduce liver damage caused by paracetamol similarly N-Acetyl-Cysteine, however, when treated with copaiba therapeutically showed increases in bilirubin, costs increasing fraction indirect.


Subject(s)
Animals , Male , Rats , Acetaminophen/adverse effects , Analgesics, Non-Narcotic/adverse effects , Chemical and Drug Induced Liver Injury/drug therapy , Fabaceae/chemistry , Plant Oils/therapeutic use , Bilirubin/blood , Chemical and Drug Induced Liver Injury/pathology , Random Allocation , Rats, Wistar , Reproducibility of Results , Time Factors , Treatment Outcome
16.
Article in English | IMSEAR | ID: sea-157400

ABSTRACT

Objective: To study the protective effect of ethyl acetate extract of Acacia catechu in carbon tetrachloride induced hepatotoxicity in albino rats. Methods: The liver damage in albino rat was induced by a subcutaneous injection of 50%v/ v carbon tetrachloride in olive oil at the dose of 2ml/kg twice a week for 14days. The hepatoprotective activity was monitored biochemically by estimating serum transaminases, serum alkaline phosphatase, serum bilirubin and serum protein after intraperitoneal injection of ethyl acetate extract of Katha(250mg/kg). Silymarin(5mg/kg.I.P) was given as a reference drug. The histopathological changes of liver samples were compared with that of control. Results: Ethyl acetate extract of Acacia catechu inhibited carbon tetrachloride induced liver toxicity in albino rats at 250mg/kg body weight as assessed by the biochemical and histological examination. Conclusion: Ethyl acetate extract of “Katha” exhibited significant hepatoprotective activity.


Subject(s)
Acacia/classification , Acacia/therapeutic use , Acetates , Adult , Animals , Carbon Tetrachloride/toxicity , Chemical and Drug Induced Liver Injury/chemically induced , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/prevention & control , Liver/toxicity , Plant Extracts/therapeutic use , Rats , Silymarin/therapeutic use
17.
Iranian Journal of Veterinary Research. 2012; 13 (1): 16-22
in English | IMEMR | ID: emr-131294

ABSTRACT

The aim of the present study was to determine the protective action of silymarin on acute toxicity due to tetracycline severe overdose in cats. Thirty healthy cats were randomly allotted into five equal groups. Cats in group A were given tetracycline [single dose 120 mg/kg, p.o.]; group B consisted of cats that received silymarin [single dose 30 mg/kg, p.o.] concurrent with tetracycline administration; groups C, D and E were treated as group B, but silymarin was administered 4, 12 and 24 h after tetracycline administration, respectively. The serum concentrations of alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], lactate dehydrogenase [LDH], BUN, serum creatinine and total and direct bilirubin were measured before tetracycline administration and 4, 12, 24 and 72 h later. A single oral administration of tetracycline increased, significantly, serum concentrations of ALT, AST, ALP, LDH in all cats of group A, after 24 h [P<0.001]. In groups B and C, levels of serum enzyme activities remained within normal values. In group D, there were changes in levels of serum enzyme activities, but the difference was not significant [P>0.05]. In group E, levels of serum enzyme activities were significantly higher than normal values [P<0.05]. The difference was significant between groups A and E with groups B and C for the serum enzymes [P<0.05]. In conclusion, silymarin can protect liver tissue against hepatotoxicity in cats with tetracycline severe overdose, particularly in the first 4 h after exposure


Subject(s)
Animals , Tetracycline/toxicity , Drug Overdose/therapy , Cats , Random Allocation , Alanine Transaminase , Aspartate Aminotransferases , Alkaline Phosphatase , Chemical and Drug Induced Liver Injury/therapy , Chemical and Drug Induced Liver Injury/drug therapy , L-Lactate Dehydrogenase
18.
Thrita Student Journal of Medical Sciences. 2012; 1 (1): 24-26
in English | IMEMR | ID: emr-127499

ABSTRACT

Cyclosporine A [CsA] is an important immunosuppressive agent; however, its clinical use is limited by several side effects such as hepatotoxicity. Vitamin C [ascorbic acid] is a very important and powerful antioxidant and protects membranes against oxidation. The aim of this study was to study protective role of vitamin C against CSA-induced hepatotoxicity. Thirty male Wister strain rats weighting 230-260g were randomly divided into 3 groups [n = 10]: group A was the control group and received placebo [Normal Saline], group B was the CSA-treated group and received 15mg/kg/day CsA for 21 days, group C was the CsA + vitamin C group and was received 200mg/kg/day vitamin C orally 3 hours before receiving 15mg/kg/day CsA. On 22[th] day rats serum obtained for measuring biochemical factors including bilirubin, alanine aminotransferase [ALT], aspartate aminotransferase [AST], triglyceride, alkaline phosphatase [ALP] and lactate dehydrogenase [LDH], total protein, and albumin. Bilirubin, ALT, AST, triglyceride, ALP, and LDH levels were lower in CsA + ascorbic acid group than that of CsA group [P < 0.05] while plasma total protein and albumin were significantly higher in CsA + ascorbic acid group than that of CsA group [P < 0.05]. In conclusion, we have shown that vitamin C administration provides protection against CSA-induced injury in rat liver function and may have hepatoprotective role in the patients experiencing CSA treatment


Subject(s)
Male , Animals, Laboratory , Cyclosporine/toxicity , Chemical and Drug Induced Liver Injury/drug therapy , Rats, Wistar
20.
Biol. Res ; 43(1): 113-125, 2010. ilus, graf
Article in English | LILACS | ID: lil-548035

ABSTRACT

Diethylnitrosamine (DEN), found in many commonly consumed foods, is widely reported to induce cancer in animals and humans. The aim of the present study was to investigate the hepatoprotective and antioxidant activities of the leaf extract of the medicinal plant Cassia fistula Linn. against diethylnitrosamine induced liver injury in ethanol pretreated rats. Albino Wistar rats, pretreated with ethanol for 15 days, were administered a single dose of DEN. Thirty days after DEN administration, hepatotocellular damage was observed histologically, along with elevated levels of serum AST, ALT, ALP, LDH, γ-GT and bilirubin and a simultaneous fall in the levels of the marker enzymes in the liver tissue. Liver oxidative stress was confirmed by elevated levels of lipid peroxidation (LPO) and a decrease in enzymic and non-enzymic antioxidants activities. Oral administration of the ethanolic leaf extract (ELE) of Cassia fistula for 30 days to ethanol + DEN treated rats significantly improved the above alterations in the markers of hepatotoxicity and oxidative stress, resulting in the reversal of most of the parameters studied and were comparable to the standard hepatoprotective drug silymarin.


Subject(s)
Animals , Male , Rats , Cassia/chemistry , Diethylnitrosamine/toxicity , Chemical and Drug Induced Liver Injury/drug therapy , Plant Extracts/therapeutic use , Antioxidants , Chemical and Drug Induced Liver Injury/enzymology , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/pathology , Ethanol/toxicity , Lipid Peroxidation/drug effects , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Rats, Wistar
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