جستجوی مقالات مرتبط با کلیدواژه « Hepatotoxicity » در نشریات گروه « پزشکی »

Gefitinib (GEF) is a targeted medicine used to treat locally advanced or metastatic non-small cell lung cancer (NSCLC). However, GEF’s hepatotoxicity limits its clinical use. This study aims to investigate the protective effect of naringin (NG) against GEF-induced hepatotoxicity. 

Fifty female ICR mice were randomly divided into 5 groups: Control, GEF (200 mg/kg), NG (50 mg/kg) + GEF (200 mg/kg), NG (100 mg/kg) +GEF (200 mg/kg), NG (200 mg/kg) +GEF (200 mg/kg). After 4 weeks of continuous administration, the mice were euthanized. The blood and liver tissue samples were collected. 

The results indicated that the GEF group showed increased liver index, liver enzyme activities, and decreased glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. Some hepatocytes showed hydropic degeneration and focal necrosis. Cell apoptosis, Cleaved-caspase3, and Poly (ADP-ribose) polymerase 1 (PARP1) increased. Transmission electron microscopy revealed the presence of numerous autophagic lysosomes or autophagosomes around the cell nucleus. Compared to the GEF group, NG can reverse these changes. 

In summary, NG alleviates GEF-induced hepatotoxicity by anti-oxidation, inhibiting cell apoptosis, and autophagy. Therefore, this study suggests the use of NG to mitigate GEF’s toxicity to the liver.

Doxorubicin, a commonly utilized anthracycline antibiotic and chemotherapeutic agent, has been associated with hepatotoxicity as an adverse effect. This study aimed to evaluate protective effects of zingerone, a bioactive compound derived from ginger renowned for its antioxidative attributes, on oxidative stress in doxorubicin-induced rat hepatotoxicity.

In this experimental study, a total of 48 male Wistar rats were allocated into six distinct groups. The first group received a control treatment of normal saline. The second group was administered an intraperitoneal dose of 20 mg/kg of doxorubicin on day 5. The third group received an oral dose of 40 mg/kg of zingerone for 8 days. The fourth, fifth, and sixth groups were administered zingerone at doses of 10, 20, and 40 mg/kg, respectively, for the same 8-day period. On day 5, all groups, except the control group, received an intraperitoneal injection of doxorubicin. Following a 72-hour interval, the animals were anesthetized, and blood samples were collected to assess serum factors. Moreover, portions of the liver tissue were subjected to histopathological analysis and assessment of oxidative stress parameters.

The activity levels of serum enzymes, including aspartate transaminase (AST), alanine transaminase (ALT), and liver malondialdehyde (MDA), increased in the doxorubicin group. Conversely, the levels of other parameters such as glutathione peroxidase (GPX), superoxide dismutase (SOD), and glutathione (GSH) decreased. However, the co-administration of zingerone effectively reversed these levels, restoring them back to normal.

These findings suggest that zingerone, particularly at a high dose, exhibit a hepatoprotective effect in the doxorubicin-induced hepatotoxicity model.

 Nowadays, the use of over-the-counter drugs such as acetaminophen (APAP) may cause severe liver injury, which can occur not only in high doses but also in therapeutic doses due to nutritional deficiency, alcoholism, or using cytochrome p450 inducers.

 In this study, the protective effect of epicatechin (EPC) was evaluated against APAP-induced hepatotoxicity to find an effective and inexpensive therapy.

 The animals were divided into preventive and therapeutic groups. In the preventive study, the animals received EPC (25, 50, and 100 mg/kg/day) for five days, and the last dose was administered 1 hour before APAP (400 mg/kg). In the therapeutic groups, the animals received EPC just before and 2 hours after the APAP injection. All the animals were killed, and blood and liver samples were taken for further analysis. The liver pathology, enzymes, and oxidant, antioxidant, inflammatory, and anti-inflammatory factors were evaluated.

 EPC significantly decreased the serum activity level of the liver biomarkers ALT and AST in the APAP-treated mice. Furthermore, the hepatic levels of thiobarbituric acid-reactive substances were noticeably lowered, and the levels of total thiol and catalase activity increased significantly with EPC. Histopathological results were strongly consistent with those of the biochemical estimations. The most effective dose was observed at EPC 100 mg/kg, and the therapeutic groups showed better results than the preventive groups.

 EPC attenuated the liver toxicity in the mice by suppressing oxidative stress and can be considered a preventive and therapeutic agent for inhibiting and resolving the liver damage induced by APAP.

According to availability of natural products, lower cost and less toxic effects compared to synthetic drugs make them an easy and excellent choice in the treatment of diseases. Silymarin “milk thistle” has been used for many years. Silymarin has antioxidant, anti-lipid peroxidation, anti-fibrotic, anti-inflammatory, and immunomodulatory properties. These effects are due to the addition of endogenous antioxidant enzymes, inhibition of neutrophil infiltration, and a reduction in serum malondialdehyde as an end product of myocardial lipid peroxide. The antioxidant and anti-inflammatory properties of silymarin may also have a protective role against carcinogens. Studies have shown that Silymaran can have protective effects against hepatotoxicity, nephrotoxicity and cardiotoxicity caused by chemical agents. A notable feature is the prowess of silymarin in shielding against reperfusion injury and inflammation, sustained by its unwavering support of anti-inflammatory and antioxidant functions .This review provides a comprehensive survey of the potentials of silymarin in cardio-protection, nephroprotection, and hepatoprotection.

Acetaminophen (APAP) is a commonly used antipyretic and pain reliever that its overdose causes acute liver toxicity. Umbelliferone (UMB) has many pharmacological effects. In this study, the hepatoprotective effect of UMB on acute hepatotoxicity induced by APAP was investigated.

Experimental approach: 

Forty-nine male mice were separated into seven groups. The control received vehicle (i.p.), UMB group received UMB (120 mg/kg, i.p.), APAP group was treated with a single dose of APAP (350 mg/kg, i.p.), and pretreated groups received N-acetylcysteine (NAC, 200 mg/kg, i.p.) or different doses of UMB (30, 60, and 120 mg/kg, i.p.), respectively before APAP. Twenty-four hours after APAP injection, mice were sacrificed and blood and liver samples were collected. Then, serum and tissue samples were investigated for biochemical and histological studies.

A single dose of APAP caused elevation in the serum liver enzymes, including alanine aminotransferase, aspartate transaminase, and alkaline phosphatase. The amounts of thiobarbituric acid reactive substances, tumor necrosis factor-alpha, and nitric oxide increased in the mice’s liver tissue. Moreover, the amount of total thiol and the activity of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) significantly diminished in the APAP group. Histological results confirmed the hepatotoxicity induced by APAP. However, UMB (more effective at 60 and 120 mg/kg) lessened APAP-induced hepatic injuries, which is comparable with NAC effects.

Conclusion and implications: 

The findings of this study provided evidence that UMB ameliorates liver injury induced by APAP through its antioxidant and anti-inflammatory effects.

3-monocholoropropan1-2diol (3MCPD) is a chlorohydrin glycerol known as a toxic substance in food processing. This substance can cause toxicity in various organs, such as the kidney, liver, reproductive system, etc. This study investigates the protective effect of resveratrol on hepatotoxicity and oxidative stress caused by 3MCPD in rats.

A total of 30 male adult rats were obtained and kept under standard conditions. Animals were divided into five groups of 6 rats, including the control group (normal saline), 3MCPD group (10 mg/kg), 3MCPD+resveratrol group (25 mg/kg), 3MCPD+resveratrol group (50 mg/kg), and 3MCPD+resveratrol (100 mg/kg) group. Injections were done intraperitoneally for 14 days. Then, 24 h after the last injection, the liver tissue was removed to evaluate oxidative parameters.

3MCDP could increase reactive oxygen species and decrease glutathione levels and mitochondrial activity; however, no significant lipid peroxidation was observed in the group receiving 3MCDP. Also, the simultaneous administration of resveratrol could reduce the level of reactive oxygen species and lipid peroxidation and increase the level of glutathione and mitochondrial activity.

3MCDP can cause toxicity in the liver of rats by inducing oxidative stress. Also, resveratrol, having antioxidant properties, can inhibit this toxicity.

Methotrexate (MTX), a folate antagonist used to treat cancer and inflammatory diseases, isknownto generate reactive oxygen species.

The research investigates the impact of dimethyl fumarate (DMF), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator, on an MTX-induced mouse hepatotoxicity model.

Forty-two mice were divided into 6 groups: control, MTX, DMF 120, and 3 groups of MTX co-treated with DMF 30, 60, and 120 mg/kg. Dimethyl fumarate was gavaged once daily for 10 days. On the fifth day, the animals received MTX 20 mg/kg intraperitoneally. On the eleventh day, the animals were sacrificed, and serum and liver samples were collected to assess the level of oxidative/anti-oxidative and apoptotic/anti-apoptotic markers.

Dimethyl fumarate prevented the increase of liver function enzymes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) induced by MTX (P < 0.001). It prevented the increase in AST and ALT levels, indicating liver recovery (P < 0.001). Furthermore, DMF restored antioxidant markers superoxide dismutase, catalase, glutathione peroxidase, and total thiol while reducing the level of thiobarbituric acid reactive substances (P < 0.001). Dimethyl fumarate also downregulated hepatic mRNA expression of caspase 3 and upregulated Bcl-2, heme oxygenase 1, and Nrf2 genes in MTX co-treated DMF groups.

Dimethyl fumarate alleviates oxidative stress and apoptosis, which may be achieved by the Nrf2/HO-1 pathway. Therefore, DMF may be clinically effective in preventing or treating MTX-induced hepatotoxicity.

Attention to the daily prescription of large amounts of drugs by doctors; In recent years, much attention has been paid to the effect of plants in the treatment and prevention of drug poisoning. Matricaria chamomilla is one of the oldest medicinal plants known to man and its use dates back to ancient Greece. In this research, the protective effect of green tea extract in hepatotoxicity caused by acetaminophen has been investigated.

So that 48 adult male mice were randomly divided into 6 groups. The control group received only physiological serum. The M. chamomile group received 250 mg/kg and (AgNP)M chamomilla received 0.5 mg/kg for 30 days. The acetaminophen group was prescribed 500 mg/kg of acetaminophen orally, and the experimental groups (acetaminophen + M. chamomile extract) were given chamomile extract with a dose of 250 mg/kg and (silver nanoparticle of M. chamomile plant + acetaminophen) (AgNP) M. chamomilla with a dose of 0.5 received mg/kg for 30 days and a toxic dose of acetaminophen was prescribed on the 29th day.

On the 31st day, blood was drawn to measure alanine transferase (ALT) and aspartate transferase (AST), and after that, the animals' livers were placed in 10% formalin for histopathological examination. The serum levels of ALT and AST enzymes in the silver nanoparticle group were significantly reduced compared to other groups. (P<0.05) so that in histopathological studies, liver necrosis, congestion of red blood cells and the accumulation of inflammatory cells in (AgNP) M. chamomilla were reduced compared to the acetaminophen group.

According to the results of this research (AgNP)M chamomilla is probably involved in liver necrosis caused by acetaminophen. It has a protective role.

Arsenic three oxide (As2O3) is the treatment choice for acute promyelocytic leukemia (APL). Little is known about possible risk factors with predictive value for toxicity caused by As2O3. Biomethylation is considered to be a major pathway of detoxification for inorganic arsenics (iAs). Arsenic Methyltransferase (AS3MT) is one of the key enzymes involved in the transfer of a methyl group from S-adenosyl-L-methionine to trivalent arsenical and plays a critical role in arsenic detoxification. Polymorphisms in hAS3MT lead to a change in the catalytic activity of the enzyme and may increase the risk of arsenic-related toxicity. In this study, we investigated the association of the AS3MT polymorphisms (rs11191439, rs3740390, and rs3740393) genes with hepatotoxicity in APL patients treated with As2O3.

Genotyping was performed in 140 adult patients with APL treated with As2O3 using PCR-RFLP for rs11191439 and tetra-primer ARMS-PCR for rs3740390 and rs3740393. The results of PCR-RFLP and ARMS-PCR were confirmed by direct sequencing of 10 % of DNA samples. The results were analyzed using SNPStats, SPSS, and FinchTV. Hepatotoxicity was graded according to the National Cancer Institute's Common Toxicity Criteria (CTC).

Hepatotoxicity was seen in 52 of the 140 patients (37.1%), with grades I and II hepatotoxicity in 40 (28.6%) and grades III and IV hepatotoxicity in 12 (8.5%) patients.  The association between the three polymorphisms and hepatotoxicity was evaluated using five genetic models and none of the three studied polymorphisms were significantly associated with hepatotoxicity.

The results of our study showed that AS3MT rs11191439, rs3740390, and rs3740393 polymorphisms are not associated with hepatotoxicity in APL patients. Genetic polymorphisms in enzymes which are involved in arsenic metabolism have been shown to have ethnicity and race-related differences. To more precisely characterize the association between AS3MT gene polymorphism and hepatotoxicity, future large-scale studies in non-Asian populations and other ethnicities are needed.

Recently, advances have emerged in medicine and pharmacotherapeutics, providing novel treatments for tuberculosis (TB). It is noteworthy that long-term drug consumption for TB treatment often leads to hepatotoxicity, which can have serious or even fatal side effects. Thus, many studies have focused on the assessment of the hepatoprotective effects of betaine, a glycine derivative. This study aimed at evaluating the effects of betaine to explore the underlying biochemical mechanisms of hepatotoxicity in rats, using combined isoniazid (INH) and rifampicin (RMP).

We used an animal model to induce hepatotoxicity with combined INH-RMP and to determine the protective effects of betaine at three doses of 125, 250 and 500 mg/kg.

Treatment with INH and RMP led to a significant upregulation of hepatic damage markers, along with marked alteration in the histopathological lesions. The results after the use of betaine were found to be satisfactory at 500 mg/kg comparable to silymarin (200mg/kg). The hepatotoxicity was also found to be associated with generation of reactive oxygen species (ROS) and oxidative stress, indicating the deterioration of the antioxidant defense system in the liver. However, pretreatment with betaine seemed to ameliorate the INH-RMP-induced hepatotoxicity, along with marked down-regulation of oxidative stress and hepatotoxicity markers.

The study findings indicated that treatment with betaine may help alleviate the INH-RMP-induced liver pathology. This was evident by the reduced inflammation and oxidative stress via mitochondrial GSH regeneration, ROS inhibition, and protection of mitochondria complex II. Further studies are warranted to investigate the validity of these outcomes.

Aflatoxin B1 (AFB1), one of the main types of aflatoxins, is the most dangerous and prevalent. Due to its side effect to the liver, AFB1 has been linked to an increased risk of hepatocellular carcinoma. This study's goal was to assess how the nanoparticles of lactoferrin (LF) protects rat liver from the toxicity caused by aflatoxin B1, as an antioxidant and anti-inflammatory compound.

Forty adult male Wistar rats (140-200g each) were divided into four groups of ten each: 1) A group of healthy animals; 2) healthy rats treated with PEE (50 mg/kg/day); 3) rats given Aflatoxin B1 (40 mg/kg/day) orally for six weeks; 4) rats injected with LF-NPs for six weeks after being intoxicated with AFB1.

The results showed that LF was successful in reducing AFB1-induced hepatotoxicity after six weeks of treatment. This was demonstrated by a significant decline in the serum ALAT, ASAT, GGT, ALP, TNF-α, IL-1β, CD4 and AFP levels, and hepatic MDA, NO, and DNA fragmentation.  Also, significant increase in the serum total protein and albumin, hepatic GSH, SOD, and CAT values were investigated. These effects were consistent with the structural restoration of the histological status of the liver.

It is possible to draw the conclusion that LF-NPs have been highly effective in reducing the oxidative stress caused by AFB1 and protecting the liver from its harmful effects. LF-NPs may be thought of as an exciting candidate for safeguarding the liver from the adverse effects of AFB1.

Cadmium (CD) causes widespread and severe toxic effects on various tissues. Studies have shown that apoptosis, inflammation, and endoplasmic reticulum stress play a role in organ damage caused by CD. Phenolic compounds with strong antioxidant effects are found in various fruits and vegetables. One of these compounds is Gallic acid (GA), which is found both free and hydrolyzable in grapes, pomegranate, tea, hops, and oak bark. Result of various studies show that GA has active antioxidant, anti-inflammatory, and anti-apoptotic properties. In our study, we investigated the mechanism of the protective effect of GA on CD-induced hepatotoxicity in rats.  In this study, 50 adult male Sprague Dawley rats weighing approximately 200–250 g were used and the rats were divided into 5 groups: Control, CD, GA50+CD, GA100+CD, and GA100. The rats were treated with GA (50 and 100 mg/kg body weight), and Cd (6.5 mg/kg) was administrated to the rats for 5 consecutive days. The liver enzymes, TB levels in serum samples, oxidative stress, inflammation, ER stresses, apoptosis marker, histopathology, 8-OHDG, and caspase-3 positivity were analyzed.  CD administration significantly increased liver enzyme levels (AST, ALT, ALP, and LDH), MDA, IL-1-β, IFN-γ, TNF-α, IL-10, IL-6, GRP78, CHOP, ATF6, p -IRE1, sXBP, Bax mRNA expression, Caspase 3, and 8-OHdG expression (P<0.05). These values were found to be significantly lower in the Control, GA100+CD, and GA100 groups compared to the CD group (P<0.05). CD administration significantly decreased the expression levels of TB, IL-4, SOD, GSH, CAT, GPX, and Bcl-2 mRNA (P<0.05). These values were found to be significantly higher in the Control, GA100+CD, and GA100 groups compared to the CD group (P<0.05). The results of the present study indicated that GA prevented Cd-induced hepatic oxidative stress, inflammation, ER stress, apoptosis, and tissue damage in rats.

Anti-tuberculosis drug-induced hepatotoxicity can result from genetic polymorphism of the isoniazid (INH) metabolizing enzyme. This study aimed to determine the effect of genetic polymorphism of N-acetyltransferase 2 (NAT2) and cytochrome P450 2E1 (CYP2E1) genes on serum isoniazid level and drug-induced hepatotoxicity.  A cross-sectional study was conducted on 120 patients (with and without hepatotoxicity) with pulmonary tuberculosis from June 2019 to April 2022 in Tehran (Iran). High-performance liquid chromatography was used to measure the serum concentration of INH and acetylisoniazid (AcINH). NAT2 and CYP2E1 genotypes were determined using polymerase chain reaction and restriction fragment length polymorphism methods. Data were analyzed using SPSS software (version 22.0) with independent two-sample t test, Chi square test, or Fisher’s exact test. P<0.05 was considered statistically significant. A total of 40 patients showed hepatotoxicity. The risk of anti-tuberculosis drug-induced hepatotoxicity was significantly higher in patients who are slow acetylator (SA) phenotype than in rapid or intermediate acetylator (P<0.001). NAT2*4/*4 genotypes were not found in patients with hepatotoxicity. The frequency of NAT2*5 and NAT2*6 haplotypes and serum INH concentration was significantly higher in patients with hepatotoxicity than in those without (P=0.003, P<0.001, and P<0.001, respectively). NAT2*4 haplotype was correlated with protection against hepatotoxicity. A combination of SA and CYP2E1 C1/C1 genotype was significantly associated with hepatotoxicity (P<0.001).  Hepatotoxicity in Iranian patients with tuberculosis was confirmed due to the presence of NAT2 SA polymorphism. Determining NAT2 and CYP2E1 genotypes and/or INH concentration can be a valuable tool to identify patients susceptible to hepatotoxicity.

Hirudotherapy is very common in traditional Iranian medicine for treating various diseases, including hyperglycemia. However, there is no scientific research to evaluate its effect on diabetes mellitus and the possible side effects.

This study aimed to evaluate the biochemical and histopathological changes in healthy and diabetic male rats treated with leeches.

This experimental study was performed on 28 male Albino Wistar rats randomly divided into control, diabetic, and two treatment groups (control and diabetic rats treated with Hirudo medicinalis). Hirudotherapy was done in 3 to 5 minutes every 5 days for 28 consecutive days. At the end of the study, blood glucose, biochemical activity of the liver, kidney, and serum lipid enzymes were evaluated by enzymatic methods. Pathological changes in liver, kidney, and pancreas tissues were studied in the experimental groups.

The levels of blood glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatinine (Cr), urea, and phosphorus significantly increased in diabetic rats treated with leeches compared to the control group (P <0.05). In addition, liver tissue changes, such as hyperemia, degeneration, inflammatory cell infiltration, andfibrous tissue formation in the portal area, were observed in diabetic rats treated with leeches. Furthermore, renal tissue changes, including renal tubular degeneration and infiltration of inflammatory cells between renal tubules, were also observed in these rats.

Leech therapy is not beneficial for alloxan-induced diabetic rats and furthermaycause hepatotoxicity and acute renal failure.

Context:

 Fungal infections are very common, and several medications are used to treat them. Azoles are prescribed widely to treat fungal infections. In addition to therapeutic effects, any drug can be accompanied by side effects in patients. One of the most important complications in this regard is liver injury. Therefore, hepatotoxicity induced by azole antifungal drugs were reviewed in this study.

Evidence Acquisition:

 English scientific papers were evaluated to review the effects of hepatotoxicity by azole antifungal agents, and the related studies' results were summarized using a table. The systematic search was implemented on electronic databases, including PubMed, Google Scholar, and Science Direct. Original articles and review articles that were published before April 1, 2022, were included in the study. Those articles without available full text or non-English articles were excluded. Also, articles that reported pediatric data were excluded.

Most studies have reported the effects of hepatotoxicity by azole antifungal agents, and their mechanisms have been described.

Clinical evaluations regarding the hepatotoxicity of antifungal agents provided in the literature were reviewed. Therefore, it is recommended to prescribe these drugs with caution in high-risk patients suffering from liver diseases, and patients should be monitored for hepatotoxicity. However, more research is needed to evaluate the hepatotoxicity of azole antifungal agents and select appropriate drugs according to cost-effectiveness and the side effects' profiles, relying on lower incidence of this liver complication.

 Cisplatin has potent antitumor properties. It has several toxic side effects, such as hepatotoxicity. It is thought that hepatotoxicity induced by cisplatin is caused by oxidative stress.

 It has shown that calcium dobesilate (CD) has potent antioxidant properties. The present study aimed to assess CD protective effects on cisplatin-induced hepatotoxicity in mice.

 In this study, 28 mice were selected randomly and were divided into four groups, including control, cisplatin (20 mg/kg, i.p., only on the first day of the experiment), Cisplatin+CD 50 (50 mg/kg CD, orally), and Cisplatin+CD 100 (cisplatin with 100 mg/kg CD, orally). A 4-day oral gavage of CD was applied to the treated groups. The mice were sacrificed on the 5th day, and serum glutamic pyruvic transaminase (SGPT), serum glutamic-oxaloacetic transaminase (SGOT), alkaline phosphatase (ALP), malondialdehyde (MDA) and reactive oxygen species (ROS) levels, superoxide dismutase (SOD), and glutathione peroxidase (GPx) enzyme activity levels in liver tissue were evaluated. Histopathological evaluation was assessed using hematoxylin and eosin-stained liver tissue sections.

 The results indicated that there was a significant increase in GSPT, SGOT, ALP, and MDA and also a significant reduction in the liver activity of SOD and GPx in cisplatin-treated animals. Treatment with CD (100 mg/kg) remarkably attenuated the GSPT, SGOT, ALP, MDA, and ROS levels. Moreover, CD (100 mg/kg) elevated the SOD and GPx activity in the liver tissue of cisplatin-treated mice.

 The findings showed that CD has a protective effect against cisplatin-induced hepatotoxicity, at least by improving the antioxidant parameters.

Hepatotoxicity is one of the most important side effects of anticonvulsant drugs. This study compared the hepatotoxicity of sodium valproate, carbamazepine, phenytoin, lamotrigine, and vigabatrin in male rats.

Based on the results, 56 rats were randomly divided into seven groups of eight and treated intraperitoneally for four weeks. Groups 1 and 2 received 500 mg/kg of carbamazepine and sodium valproate, and groups 3, 4, and 5 were injected with 200 mg/kg of phenytoin, 200 mg/kg lamotrigine, and 500 mg/kg vigabatrin, respectively. As control groups, the sixth and seventh received distilled water and sesame oil. Biochemical parameters such as alanine aminotransferase (ALT), aspartate transaminase (AST), and γ-glutamyl transferase (GGT) in the serum samples, as well as malondialdehyde (MDA) and glutathione (GSH) contents in liver homogenates, were measured at the end of the experiment.

MDA levels in carbamazepine and phenytoin groups were significantly higher than that in sodium valproate, lamotrigine, vigabatrin, and control groups (P<0.05). GSH levels in carbamazepine and phenytoin groups were meaningfully higher compared to the groups that received sodium valproate (P<0.05), vigabatrin, and control groups (P<0.001). Based on the results, the GGT level in the carbamazepine group was remarkably higher in comparison with the other groups (P<0.01). ALT and AST represented considerably higher levels in the phenytoin group compared to the vigabatrin, sodium valproate, and control groups (P<0.01).

Overall, carbamazepine-induced hepatotoxicity caused the most significant changes in GSH, GGT, and AST. The induction of hepatotoxicity with sodium valproate had the least effect on enzymes and was significantly different compared to carbamazepine and phenytoin groups. Because of no hepatic metabolism, the level of biomarkers did not demonstrate a considerable difference between vigabatrin and the control groups.