Biochemical Mechanisms of Oxidative Stress in Animals Exposed to Hexavalent Chromium Compounds in the Case of Isoniazid–rifampicin Hepatitis

Camel's products are regarded historically as having a high-quality source of nutrients and used to treat various ailments. In particular, camel's milk and urine have been applied to treat disorders stemming from persistent liver dysfunction. The objective of this study was to explore the hepatoprotective effects and potential mechanisms of camel's biological fluids (i.e., milk and urine) on D-Gal-induced liver injury in mice. Mice was allocated randomly into four groups of six mice each. Group 1 administered normal saline orally (p.o.) for 14 days. Group 2 were given normal saline for 14 days and D-GalN (800 mg/kg i.p.) 24 hr before the last saline administration and served as disease control. Group 3 and 4 were treated orally with camel's milk and urine (10 mL/kg) for 14 days, respectively, and 24 hr before the last dose D-Gal dose (800 mg/kg i.p.). At the end of the experiment, the blood samples were collected in heparinized tubes for biomarkers' analysis and liver tissues were harvested for histology. A marked increase in liver function tests (i.e., AST, ALT, GGT, ALP, LDH and bilirubin) was observed in the D-Gal-treated mice compared with the control group (p < 0.05). Treatment with camel's milk and urine significantly ameliorated hepatic injury and improved liver histology findings. The protective mechanism of camel's milk and urine also appeared to be dependent on the downregulation of NF-κB and the reinstatement of antioxidant enzyme levels via the activation of the Nrf2/HO-1 pathway. The biological fluids or excreta of camel (i.e., milk and urine) could have a potential application in the management acute hepatic injury and future clinical testing is warranted. RezumatÎncă din cele mai vechi timpuri, fluidele biologice ale cămilei, considerate o sursă de nutrienți de înaltă calitate, au fost folosite pentru a trata diverse afecțiuni. Laptele și urina de cămilă au fost utilizate în special pentru a trata disfuncții hepatice persistente. Scopul acestui studiu a fost de a explora efectele hepatoprotectoare și mecanismele potențiale ale fluidelor biologice de cămilă asupra leziunilor hepatice induse de D-Gal la șoareci. Animalele au fost repartizate aleatoriu în patru grupuri de câte șase șoareci fiecare. Grupului 1 i s-a administrat soluție salină normală pe cale orală (p.o.) timp de 14 zile. Grupului 2, grupul control, i s-a administrat soluție salină timp de 14 zile și D-GalN (800 mg/kg i.p.) cu 24 de ore înainte de ultima administrare. Grupurile 3 și 4 au fost tratate oral cu lapte de cămilă și urină (10 ml/kg) timp de 14 zile, respectiv cu 24 h înainte de ultima doză au primit D-GalN (800 mg/kg i.p.). La sfârșitul experimentului, au fost recoltate probe de sânge în tuburi heparinizate pentru analiza biomarkerilor, iar țesuturile hepatice au fost recoltate pentru histologie. La șoarecii tratați cu D-Gal s-a observat o creștere marcată a testelor funcționale hepatice (AST, ALT, GGT, ALP, LDH și bilirubină) în comparație cu grupul control (p < 0,05). Tratamentul cu lapte și urină de cămilă a ameliorat semn...

Section: Resultssupporting

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Amelioration of Hepatic Injury by Camel’s Biological Fluids Through the Modulation of Nf-Κb and Nrf2/Ho-1 Singling Pathway

ALKHARFY¹

2023

“…The current in vitro study aimed to investigate the potential hepatoprotective effect of AT against EEinduced damage in HepaRG cells, considering the following aspects: (i) DIH represents one of the main causes leading to drug withdrawal from therapeutic use [14]; (ii) many drugs have been already classified as hepatotoxic, among which OCs were associated with more than 100 cases of drug-induced liver damage, being included in the category A of hepatotoxicity according to the LiverTox database [3]; (iii) EE is the main estrogenic component of modern OCs which was previously shown to exert hepatotoxicity in vivo [22]; (iv) an effective solution for ameliorating the hepatotoxicity induced by EE might be the use of antioxidants since oestrogens in excess were previously showed to enhance oxidative stress in hepatic cells through various mechanisms such as the depletion of cellular antioxidants (e.g., glutathione) [34]; and (v) AT is a potent radical scavenger with hepatoprotective activity [25]. The HepaRG cells were selected as an experimental model for this study because they represent a highly available alternative to primary human hepatocytes, retain the major functions of the liver, and are widely used in toxicological evaluations [4,10].…”

Section: Resultsmentioning

confidence: 99%

In Vitro Evaluation of Alpha-Tocopherol as Potential Agent in Combating the Hepatotoxicity Induced by Ethinylestradiol

ILIESCU

2023

Drug-induced hepatotoxicity (DIH) represents the main cause of drug withdrawal from therapy. Despite their numerous benefits, oral contraceptives (OCs) present several adverse effects, including a high risk of liver complications. Thus, the main objective of this in vitro study was to assess the potential of alpha-tocopherol (AT) in reducing the cytotoxicity of ethinylestradiol (EE), the primary ingredient of modern OCs, against the HepaRG cell line. The results showed that AT exerted no cytotoxicity in HepaRG cells at the tested concentrations, while EE reduced cell viability and confluence, altered cellular morphology, and induced apoptotic-like nuclear features at 100 µM. These cytotoxic effects were reversed by the co-treatment of EE 100 µM with AT 1 µM -the viability, morphology, and nuclear parameters of the treated cells were similar to those of control cells. However, at 100 µM, AT significantly augmented the hepatotoxicity of EE 100 µM, leading to the highest reduction in cell viability, loss of confluence, fragmentation of cell nuclei, increase of the apoptotic index, and reduction of nuclear area and circumference. Further studies should investigate the hepatoprotective effect of AT at low concentrations against EE-induced liver damage, also considering the potential toxicity resulting from their co-administration in high doses. RezumatHepatotoxicitatea reprezintă principala cauză a retragerii medicamentelor din terapie. Deși au numeroase beneficii, contraceptivele orale (CO) prezintă o serie de reacții adverse, printre care se numără și riscul crescut de apariție a complicațiilor la nivel hepatic. Obiectivul principal al acestui studiu in vitro a fost evaluarea eficienței alfa-tocoferolului (AT) în combaterea citotoxicității indusă de etinilestradiol (EE), componenta majoră a CO moderne, asupra liniei celulare HepaRG. Rezultatele au arătat că AT nu a prezentat citotoxicitate asupra celulelor HepaRG la concentrațiile testate, însă EE la concentrația de 100 µM a redus viabilitatea celulară și confluența, a afectat morfologia celulară și a determinat alterări la nivel nuclear similare procesului de apoptoză. Aceste efecte citotoxice au fost reduse prin asocierea EE 100 µM cu AT 1 µMvaloarea viabilității, morfologia celulară și aspectul nuclear al celulelor tratate au fost similare cu cele ale celulelor Control. Cu toate acestea, la concentrația de 100 µM, AT a crescut hepatotoxicitatea indusă de EE 100 µM, ducând la cea mai mare scădere a viabilității celulare, reducere a confluenței și fragmentare a nucleilor celulari. Efectul hepatoprotector al AT la concentrații mici împotriva hepatotoxicității indusă de EE necesită studii suplimentare, considerând potențialul toxic al co-administrării acestor compuși la doze mari.

“…Many drugs may interfere with demineralization mechanisms, including glucocorticoids and hepatitis antiviral therapy. It is possible that even antituberculosis therapy that may cause toxic hepatitis may interfere with bone mass loss, as the period of treatment is long, especially in nonresponsive patients [1,11]. Some limitations were noted in this study.…”

Section: Table IV Correlations Between the Age Of Hbv Patients And Th...mentioning

confidence: 89%

“…The regression models were adjusted according to the F-test of the ANOVA. Significant results at 0.05 and 0.01 level are marked with * and ** respectively Bone metabolism alterations are a frequent complication of liver diseases regardless of their aetiology [11,18]. Osteoporosis and osteopenia are the most cited ones, while osteomalacia is a very rare complication, mostly associated with longstanding illnesses [10].…”

Section: Correlations Analysis Between Bmd Measurements and Anthropom...mentioning

confidence: 97%

Reduced Bone Mineral Density in Young, Non-Cirrhotic Patients With Chronic Viral Hepatitis

ȚUCULEANU¹

2022

Bone anomalies are well-known complications of advanced hepatic diseases, but a relationship with non-cirrhotic hepatopathies remains to be confirmed. In this study, we investigated young adults with viral hepatitis B or C to determine whether their condition may impact bone loss and which factors influence this phenomenon. Subjects were divided in 3 groups. Descriptive statistics were based on anthropometric, bone density and disease-related parameters (viral load, disease length, fibrosis grade and treatment history). We compared bone demineralization between each group and aimed to determine associations between anthropometric or disease-related parameters and bone density measurements. Multiple linear regression analysis was performed to identify predictors for bone demineralisation. Reduced bone mineral density prevalence was of 11%, most of them males in hepatitis B group and, respectively 11%, most of them females in hepatitis C group, 5 times greater than the control group. Hepatitis C females had lower Z-scores than control females at the hip. In hepatitis B patients, age, male gender, fibrosis grade, disease length and antiviral therapies were found to play an important role in bone demineralization. In hepatitis C patients, most of the anthropometric characteristics (body mass index and female gender) had quantifiable impact on bone loss. These patients could be considered for early screening and treatment. RezumatDemineralizarea osoasă este o complicație cunoscută a afecțiunilor hepatice avansate, dar prezența acesteia în stadiile precirotice nu a fost confirmată încă. În acest studiu, am investigat pacienți tineri cu hepatită virală B sau C pentru a determina dacă patologia lor influențează mineralizarea osoasă și ce factori contribuie la acest proces. Pacienții selectați au fost incluși în 3 grupuri de studiu. S-au realizat statistici descriptive bazate pe parametrii antropometrici, osteodensitometrici și legați de boală (încărcătura virală, durata bolii, gradul fibrozei și istoricul de tratament). S-a comparat mineralizarea osoasă între cele 3 grupuri și, prin analiza corelațiilor, am investigat asocierile dintre parametrii antropometrici și legați de boală și mineralizarea osoasă. O analiză de regresie liniară multiplă a determinat factorii de predicție ai demineralizării. Prevalența demineralizării a fost de 11%, majoritatea bărbați, în grupul cu hepatită B și de 11%, majoritatea femei, în grupul cu hepatită C, de 5 ori mai mare față de grupul control. Femeile cu hepatită C au avut scoruri Z mai mici decât femeile control la nivelul șoldului. În cazul hepatitei B, vârsta, sexul masculin, gradul fibrozei, durata bolii și tratamentul antiviral au avut un impact negativ asupra mineralizării. În cazul hepatitei C, parametrii antropometrici (indicele de masă corporală și sexul feminin) influențează demineralizarea. Acești pacienți trebuie avuți în vedere pentru screening și tratament precoce.