Hepatotoxicity In Rats Research Articles (Page 1)

Radioprotective effects of quercetin and curcumin on hepatotoxicity and nephrotoxicity in male albino rats

Current study was an attempt to unravel the molecular mechanisms underlying the protective role of Coenzyme Q10 (CoQ10) in isoniazid (INH) and rifampicin (RIF)-induced hepatotoxicity. The animals were treated with INH and RIF (50 mg/kg b.w.) for 28 days. The protective role of concomitant administration of CoQ10 (10 mg/kg b.w.) was evaluated and compared with that of silymarin (25 mg/kg b.w.). Blood and liver tissue of the study animals were used for the evaluation of antioxidant, immunological and mitochondrial parameters and the estimation of total ROS. The expression of inducible nitric oxide synthase (iNOS), nuclear factor kappa-B (NFκB) and peroxisome proliferator-activated receptor gamma (PPAR-γ) were analysed by real time reverse transcriptase polymerase chain reaction (RT-PCR). INH and RIF caused depletion of plasma antioxidant enzymes, nonenzymatic antioxidants and mitochondrial parameters and also resulted in increased lipid peroxidation and ROS as compared to the normal control rats. The serum levels of tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were found to be increased in the INH and RIF treated rats. INH and RIF treated rats showed increased expression of iNOS and NFκB and reduced expression of PPAR-γ. Coenzyme Q10 was able to restore normal expression of iNOS and NFκB while significantly increasing the expression of PPAR-γ. It was found that concomitant administration of CoQ10 was able to restore near normal antioxidant status in INH and RIF treated rats.

Ameliorative effect of folic acid and vitamin B12 against Ivermectin-induced hepatotoxicity, renal toxicity, oxidative stress and immunohistochemical changes in male albino rats

Paracetamol overdose is a primary cause of drug-induced hepatotoxicity, mediated through oxidative stress pathways. This study determined the protective efficacy of Allium cepa methanolic extract against paracetamol-induced liver damage. Methanol extract yield of Allium cepa and phytochemical screening was carried out using standard methods. Thirty six (36) adult male albino rats comprising of six (6) normal and thirty(30) hepatotoxic rats were used for this study. Toxicity was induced using paracetamol (500 mg/kg) orally. Treatment with the extract and observation was done for 21 days. Experimental rats were divided into six groups: normal control, paracetamol control (500 mg/kg), and four treatment groups receiving paracetamol plus Allium cepa extract (50, 100, 150, and 200 ml/kg). Liver functions were determined through liver biomarkers (ALT, AST, ALP, bilirubin, proteins, albumin and globulin), oxidative stress parameters (MDA, GSH, CAT, SOD), and histopathological examination. The percentage yield of the methanol extract of Allium cepa was found to be 36%w/w. Phytochemicals screening recorded appreciable amount of saponin, alkaloid, flavonoids cardiac glycosides etc. Paracetamol administration caused significant elevation of ALT (53.00 ± 2.45 IU/L) and AST (33.20 ± 2.59 IU/L) compared to normal controls. Co-treatment with Allium cepa extract demonstrated dose-dependent protection, with the 200 ml/kg dose normalizing ALT (26.60 ± 1.52 IU/L) and AST (22.00 ± 2.12 IU/L). The extract significantly reduced oxidative stress by lowering MDA and elevating GSH, CAT, and SOD activities. Histopathological analysis confirmed preserved liver tissue architecture in extract treated groups. The results indicate that A. cepa extract may have provided significant protection against paracetamol-induced hepatotoxicity through antioxidant mechanisms and functional preservation, supporting its potential therapeutic application.

ABSTRACTPaclitaxel (PTL) is widely used in chemotherapy; however, its efficacy is compromised by the risk of liver toxicity. This is the first study to investigate the protective effect of betaine (BTN) against PTL‐induced liver injury. Rats were randomly divided into five experimental groups (n = 7 per group): control (saline), BTN (100 mg/kg/day), PTL (2 mg/kg/day), PTL + BTN (2 and 50 mg/kg/day), and PTL + BTN (2 and 100 mg/kg/day). After the rats received 2 mg/kg body weight PTL intraperitoneally for the first five consecutive days, BTN was administered orally for 10 days. Our results indicate that BTN restores liver antioxidant levels (SOD, FRAP, and GSH), improves liver function by lowering AST and ALT levels, and attenuates PTL‐induced lipid peroxidation. In the livers of PTL‐treated rats, BTN significantly decreased the levels of NF‐κB and TNF‐α proteins and the ratio of caspase‐3/pro‐caspase‐3, whereas it increased the levels of Nrf2, LC3‐II/LC3‐I, and Bcl‐2. In summary, the results of this study suggest that BTN may ameliorate PTL‐induced liver injury by regulating oxidative stress, inflammation, apoptosis, and autophagy.

Nigella sativa is a promising natural remedy for liver problems because of its cytoprotective, hypolipidemic, and antioxidant properties. Here, we looked at the possible defense of Nigella sativa seed (NSS) against hepatotoxicity in rats caused by lipopolysaccharide and D-galactosamine. For 30 days, 36 adult Wistar albino rats were evenly and randomly split into six groups in order to achieve this goal. Lipopolysaccharide (30μg/kg b.wt., i.p.) and D-galactosamine (300mg/kg b.wt., i.p.) were given as supplements to the second group, whereas the control group received no therapy. Nigella sativa alcoholic extract (500 mg/kg b. wt orally) was added as a supplement to the third group. The fourth group was given DGalN/LPS along with 500 mg/kg.B.wt. of Nigella sativa alcoholic extract. Group VI was given Thymoquinone (30 mg/kg b.wt. orally) in combination with D-GalN/LPS, whereas Group V was given Thymoquinone (40 mg/kg b.wt. orally) as a regular medication. NSS succeeded in boosting serum reduced glutathione level along with hemoglobin level. It reduced lipid peroxides in the serum along with serum bilirubin and ESR. NSS was successful in raising both the hemoglobin and serum reduced glutathione levels. Serum bilirubin, ESR, and lipid peroxides were all decreased. NSS's anti-apoptotic and antioxidant properties effectively guarded against the hepatotoxicity of DGalN/LPS. These results are extremely important since they highlight the use of NSS in our food sector and as a traditional medicine treatment to combat liver problems

Chlorpyrifos (CPF) is a widely used pesticide known for its hepatotoxic effects. Melissa officinalis L. is a medicinal herb, recognized in Persian medicine for its diverse biological activities and protective effects against poisons. This study aimed to study the protective effects of M. officinalis against CPF-induced hepatotoxicity in male rats. Experimental groups included control, sham, CPF (10mg/kg), M. officinalis (500mg/kg), and combinations of CPF with M. officinalis (100, 250, and 500mg/kg). M. officinalis dried powder was administered orally for four weeks, with CPF introduced in the third week. Following treatment, biochemical parameters include serum levels of AST, ALT, ALP, LDH, oxidative stress in liver tissue, acetylcholinesterase (AChE) activity and paraoxonase-1 (PON) activity in the serum, and PON1 gene expression in the liver, along with histological alterations in liver tissue were assessed. Results indicated that CPF-treated groups had significantly increased AST, ALT, and LDH levels in serum and induced oxidative stress in liver tissue, while M. officinalis ameliorate these changes in a dose-dependent manner. Histological analysis showed M. officinalis at 250mg/kg dose prevented CHF-induced inflammation and degeneration in the liver, but the 500mg/kg dose resulted in cytoplasmic vesicle lesions and inflammatory cell infiltration. AChE activity was significantly inhibited by CPF, and M. officinalis did not mitigate this inhibition. PON activity and gene expression were also unaffected by M. officinalis treatment. In conclusion, M. officinalis effectively mitigated CPF-induced liver damage and oxidative stress at low to medium doses, while higher doses caused tissue damage.

Pre- and post- treatment effect of water-soluble phenolics from date palm (Phoenix dactylifera L.) fruits in cisplatin-induced hepatotoxicity in rats

Evaluation of the protective effect of liquorice, curcumin, and marjoram on oxidative stress in CCL4 hepatotoxicity in rats

Dose-dependent hepatotoxicity in Norway rat: Investigating the effects of methadone and morphine on liver gene expression and function.

Mussaenda erythrophylla, a botanical treasure, has revealed numerous pharmacological potentials warranting scientific investigation. The hydroalcoholic extract of its leaves demonstrated dose-dependent analgesic, anti-inflammatory, and antipyretic activities. Notably, the leaf extract exhibited robust antioxidant activity, comparable to vitamin C, as evidenced by DPPH and NO assays. Methanolic extracts of the plant showed promising in vitro anthelmintic activity against earthworms. Additionally, root extracts in chloroform and ethanol significantly increased urine volume. Methanolic and ethyl acetate extracts of the plant protected against CCl4-induced hepatotoxicity in rats, as indicated by decreased serum enzyme levels. The plant extracts also demonstrated anti-arthritic properties through proteinase inhibition and denaturation assays. Ethanolic leaf extract showed potent anti-plasmodial activity against P. falciparum, with minimal toxicity. Furthermore, the leaf extract effectively inhibited carbon steel corrosion in a 1M HCl solution. Phytochemical analysis of floral extracts revealed the presence of steroids and triterpenoids. Keywords: Herbal remedy, Analgesic, antioxidant, Anti-arthritic, Anti-plasmodial, Corrosion inhibition

Oroxylum indicum is an important Ayurvedic plant from the "Dasamoola" group, traditionally used as a detoxifying agent. This study evaluates the protective effects of the root bark methanol extract of O. indicum (ORX) against acetaminophen-induced hepatotoxicity and cisplatin-induced nephrotoxicity in rats. The doses of ORX used in the study were selected based on the previous toxicity analysis (200 mg/kg and 400 mg/kg doses). Acetaminophen administration increased serum liver function markers (AST, ALT, ALP, bilirubin), while ORX and silymarin treatments significantly reduced these levels (p<0.01). ORX administration also reversed the acetaminophen-induced depletion in hepatic redox balance as indicated in terms of SOD, GPx, GSH and lipid peroxidation. Corroborating these, the changes in the hepatic normal architecture induced by acetaminophen were also reversed by the pre-treatment with ORX. Similarly, the cisplatin administration resulted in strong myelosuppression and nephrotoxicity. In cisplatin-exposed rats, renal oxidative stress markers worsened, and serum renal function parameters were elevated. On the contrary, the pre-treatment with ORX alleviated the cisplatin-induced myelosuppression and redox imbalance in the renal tissues; further, it also restored the renal histology to near normal. Overall, O. indicum root bark extract effectively mitigated drug-induced liver and kidney damage, likely through redox balance restoration.

Alcoholic fatty liver disease (AFLD) is a leading cause of chronic liver disease worldwide, contributing to significant morbidity and mortality. Despite its growing prevalence, no FDA-approved pharmacological treatments exist, leaving lifestyle modifications as the primary intervention. AFLD pathogenesis involves a complex interplay of lipid accumulation, oxidative stress, insulin resistance, and inflammation, highlighting the need for innovative therapeutic approaches. However, sodium orthovanadate (SOV), an inorganic vanadium-based compound, is a potent inhibitor of protein tyrosine phosphatases (PTPs), including PTP1B-a key regulator of insulin signalling and metabolic homeostasis. SOV has demonstrated insulin-mimetic properties and has shown promise in preclinical models of metabolic disorders. Given the emerging role of PTP1B in hepatic insulin resistance and lipid dysregulation, we hypothesize that SOV may offer therapeutic benefits in AFLD by modulating biochemical parameters and oxidative stress in liver. In this study, we investigate the effects of SOV in two rodent models of AFLD: (1) alcohol-induced liver disease and (2) high-fat diet plus alcohol-induced liver disease. We assess Biochemical Parameters like alkaline Phosphatase (ALP), aspartate amino transferase (AST), alanine amino transferase (ALT), lactate dehydrogenase (LDH), total bilirubin, cholesterol, uric acid, triglyceride. Tissue analysis like TBARS/MDA activity, Glutathione (reduced GSH) assay, Glutathione peroxidase (GPx) activity, Superoxide Dismutase, Catalase activity, and Histopathology to determine whether SOV can mitigate AFLD progression. Our research shows that SOV has promise as a treatment for fatty liver disease brought on by alcohol. Improvements in oxidative stress control,biochemical markers most likely mediate its hepatoprotective benefits. By uncovering the therapeutic potential of SOV, this study may pave the way for novel pharmacological strategies to combat fatty liver diseases.

ABSTRACT Tartrazine, a coal tar-derived azo color, is utilized in food, drinks, cosmetics, and pharmaceuticals. Its azo group catabolizes in the gut, poisoning the liver. This study investigated the efficacy of melatonin, an endogenous antioxidant from the pineal gland against hepatotoxicity in tartrazine-intoxicated rats. Thirty-two adult male wistar albino rats were allocated into four groups: control group, melatonin group (10 mg/kg), tartrazine-treated group (7.5 mg/kg), and tartrazine + melatonin-treated group (7.5 mg/kg tartrazine + 10 mg/kg melatonin). Doses were taken daily for 4 weeks. Melatonin’s influence on hepatotoxicity was assessed by monitoring liver enzyme activity, antioxidant state, apoptotic and inflammatory markers, DNA fragmentation, histological and ultrastructural changes. Rats exposed to tartrazine exhibited elevated liver enzymes, oxidant-antioxidant imbalance, and elevated hepatic inflammatory markers (TNF-α, IL-6). Tartrazine also damaged DNA and induced histological and ultrastructural alterations in liver tissue, as shown by the comet assay. Alpha-fetoprotein (AFP) and proliferating cell nuclear antigen (PCNA) were strongly expressed in immunohistochemistry. In rats, melatonin significantly reduced all tartrazine effects. Conversely, melatonin treatment significantly alleviated all aforementioned effects induced by tartrazine in rats by decreasing liver enzymes, elevating antioxidant enzymes, and reducing hepatic inflammatory markers. Enhanced histological assessment and the ultrastructure of the liver was detected following melatonin use. The use of melatonin may safeguard against tartrazine-induced hepatic DNA damage. In conclusion, the current findings indicate that tartrazine administration has detrimental health effects and deleterious impacts on liver function and structure. Melatonin mitigated tartrazine-induced liver damage via antioxidant, anti-inflammatory, and anti-apoptotic pathways.

Liver disease is becoming the most common cause of death all over the world. Each year 5.9 % of global death is associating with alcohol-related liver disease (ALD), The current study focuses on readily available natural resources. S.amaranthoides and P. foetida plants hydroethanolic extracts demonstrated a significant hepatoprotective potential on CCl4-induced hepatotoxic Wistar rats, Alteration of serum SGOT, SGPT and Alkaline Phosphatase concentration caused by CCl4 administration was recovered by using combined plant extracts. Treatment with 500mg/kg of both plants' hydroethanolic extracts, Sphaeranthus amaranthoides and Paerida foetida, resulted in a significant decrease in the levels of ALT, AST, ALP, total protein, total bilirubin, as well as a significant increase in the levels of MDA and GSH when compared to the disease control group. When compared to the standard group given silymarin at a dose of 10mg/kg body weight, histopathological studies revealed a good hepatoprotective effect. Combined plant extracts have shown a potential impact, may be due to presence of flavonoids and phenolic content. As both plants are edible, they are safe and effective.

Butein mitigates 5-FU-triggered hepatotoxicity via antioxidant, anti-inflammatory, and anti-apoptotic pathways

Syringic acid (SYA) is a significant phenolic compound with the potential for various biomedical uses, including uses of its hepatoprotective properties. Doxorubicin (DOX) is a drug used in the treatment of several tumors, but its side effects, particularly hepatotoxicity, limit its effectiveness. This study investigated the therapeutic effects of SYA on DOX-induced hepatic injury in rats. Molecular docking studies were performed using AutoDock Vina. Five groups of Sprague–Dawley rats (eight in each group) were studied. Gp1 was a negative control group; Gps2–5 was administered intraperitoneally (i.p.) with DOX at a dosage of 4 mg/kg once a week for a month; and Gp2 was left as a positive control group. Gps3–5 received oral SYA at doses of 25, 50, or 75 mg/kg/day, respectively, for a month. Histopathological, molecular, and biochemical analyses were conducted one month after the last SYA dosages were given. The findings demonstrated that by reversing biochemical changes and reducing oxidative stress and inflammation, SYA therapy considerably reduced DOX-induced hepatotoxicity in rats. These results implied that SYA may lessen the hepatotoxicity that DOX causes in rats.

A potent anticancer drug, doxorubicin (DOX), has substantial off-target hepatotoxicity, which limits its clinical use. The current study aimed to investigate the hepatoprotective effect of aegeline against DOX- induced hepatotoxicity in rats. Four groups of rats were randomly divided into following: Group I- Control (saline), group II - DOX, group III DOX + aegeline (5mg/kg/p.o.), and group IV DOX + aegeline (10mg/kg/p.o.). Various biochemical parameters such as alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bilirubin, oxidative stress markers such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO), inflammatory markers such as interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), nuclear factor kappa-B (NF-κB) and apoptosis markers, i.e. Bax (Bcl-2-associated X protein), B-cell lymphoma 2 (Bcl2), caspase-3 and caspase-9 were performed. Additionally, histopathology and molecular docking were performed. Administration of aegeline at both tested doses led to a significant (P < 0.05) reduction in liver enzyme levels such as ALT, ALP, and AST-in rats with DOX-induced hepatotoxicity, indicating improved liver function. Antioxidant defenses were also markedly enhanced in the aegeline-treated groups, as evidenced by increased levels of GSH, SOD, and CAT compared to the DOX-only group. In terms of inflammation, aegeline treatment significantly (P < 0.05) lowered the concentrations of key inflammatory cytokines, including IL-6, IL-1β, TNF-α, and the transcription factor NF-κB. This suggests a strong anti-inflammatory effect. Regarding apoptosis, the expression levels of pro-apoptotic markers-Caspase-3, Caspase-9, and Bax were notably decreased in the aegeline-treated rats, while levels of the anti-apoptotic protein Bcl-2 were elevated, pointing to a protective role against DOX-induced cell death. Molecular docking analysis further supported these findings, showing favorable interactions between aegeline and several target proteins. Notably, aegeline exhibited the strongest binding affinity with Bcl-2 (- 6.568kcal/mol), primarily through hydrophobic interactions, suggesting potential molecular targets contributing to its therapeutic effects. The present study accredited the hepatoprotective effect of aegeline (5 and 10mg/kg) by ameliorating Dox-induced hepatotoxicity in an experimental animal model.

Background: The global rise in liver diseases associated with environmental toxins and lifestyle factors has intensified interest in functional foods with hepatoprotective properties. Moringa oleifera, a multipurpose, edible plant with established nutritional value, represents a promising candidate as a functional food due to its bioactive compound profile and traditional medicinal applications. Objective: This investigation evaluated the antioxidant and hepatoprotective properties of methanol extract from Moringa oleifera leaves (MOEXT) against carbon tetrachloride (CCl₄)-induced liver damage in experimental rats, with a specific focus on its potential as a functional food ingredient for liver health. Methods: We assessed MOEXT's antioxidant capacity through DPPH scavenging, ABTS neutralization, and ferric reduction assays. Safety evaluation followed OECD protocol 423. Hepatoprotective evaluation utilized the CCl₄ liver damage model in Wistar rats, with assessment of liver biomarkers, oxidative stress indicators, and tissue morphology. Functional food applications were evaluated based on bioactive compound stability and efficacy. Results: MOEXT exhibited concentration-dependent antioxidant properties with IC₅₀ values of 28.4 ± 2.1 μg/mL (DPPH) and 31.7 ± 1.8 μg/mL (ABTS). Safety studies indicated LD₅₀ exceeding 5000 mg/kg, supporting its food safety profile. MOEXT significantly (p &lt; 0.001) prevented CCl₄-induced increases in liver enzymes (AST, ALT, ALP) and bilirubin concentrations. The extract enhanced antioxidant enzyme function (SOD, CAT, GPx) and decreased lipid peroxidation markers. Microscopic examination confirmed protective effects on liver structure, demonstrating the potential for incorporating M. oleifera into functional food products. Conclusion: MOEXT demonstrates significant antioxidant and hepatoprotective activities, supporting its development as a functional food ingredient for liver health maintenance. These findings provide scientific validation for incorporating M. oleifera into nutraceutical and functional food products targeting hepatic wellness. Keywords: Moringa oleifera, functional foods, nutraceuticals, liver protection, antioxidant activity, bioactive compounds, agricultural biotechnology

Background/Objectives: Thiamethoxam (TMX) is one of the most extensively utilized insecticides of the neonicotinoid family; however, its application is associated with notable toxic effects on multiple organs of mammals. Our purpose was to explore the potential hepatoprotective effect of taurine (TAU) and/or gallic acid (GA) against TMX-induced liver damage, with an emphasis on their role in regulating SIRT-1/PGC-1α, NF-κB/iNOS, and p53/Bax/caspase-3 pathways. Methods: Rats were assigned to seven groups (n = 6) and gavaged daily for 28 days with saline (control group), TAU at 50 mg/kg, GA at 20 mg/kg, TMX at 78.15 mg/kg, TMX + TAU, TMX + GA, and TMX + TAU + GA. Results: The findings revealed that TAU and/or GA attenuated TMX-induced liver injury, as demonstrated by the restoration of hepatic performance hallmarks and histological structure. TAU and GA mitigated TMX-mediated oxidative stress and boosted the antioxidant defense mechanism by upregulating the transcription levels of SIRT-1, PGC-1α, Nrf2, and HO-1. Moreover, TAU and GA suppressed TMX-associated inflammatory response by increasing IL-10 concentration and lowering the levels of NF-κB, IL-1β, and iNOS; the mRNA levels of NLRP3; and TNF-α immunoexpression. Both compounds, individually or concurrently, exerted an anti-apoptotic effect in TMX-treated rats, evidenced by increased Bcl-2 expression and reduced p53 mRNA level, Bax expression, and caspase-3 concentration. Conclusions: TAU and/or GA may be regarded as promising remedies that can alleviate TMX-induced hepatotoxicity by activating SIRT-1/PGC-1α signaling and abolishing inflammation and apoptosis.