Hepatotoxicity In Rats Research Articles

Nitazoxanide mitigates methotrexate hepatotoxicity in rats: role in inhibiting apoptosis and regulating endoplasmic reticulum stress

ObjectivesHepatotoxicity is a severe outcome of methotrexate (MTX) therapy, limiting its clinical use and contributing to its related morbidity and mortality. This study investigated the hepatoprotective effects of nitazoxanide (NTZ), an antiprotozoal drug, against MTX-induced hepatotoxicity and whether endoplasmic reticulum (ER) stress-modulation underlies the expected beneficial effects of NTZ.MethodsThirty-six rats were allocated to six groups, one control group and five MTX groups, where induction of hepatotoxicity was achieved via injecting MTX (20 mg/kg). Groups were assigned as MTX-vehicle, NTZ-100, and NTZ-200 groups (at 100 and 200 mg/kg/day, gavage, respectively), N-acetyl cysteine (NAC) group (500 mg/kg), and 4-phenyl butyric acid (4-PBA) group (150 mg/kg, i.p). Liver function enzymes in serum, hepatic oxidative stress, proinflammatory cytokines, apoptosis, and ER-stress biomarkers were assessed. A histopathological examination was performed.ResultsTreatment with NTZ lessened the serum liver enzymes, reduced malondialdehyde (lipid peroxidation product), enhanced antioxidant capacity, attenuated proinflammatory cytokines, and suppressed apoptosis. The protective effect of NTZ was dose-dependent, and the findings observed with the high-dose NTZ were similar to those obtained with the ER-stress inhibitor (4-PBA).ConclusionNTZ exerted a hepatoprotective effect in MTX-challenged rats that is mediated via modulation of ER stress and inhibiting apoptosis.

Avenanthramide-C ameliorate doxorubicin-induced hepatotoxicity via modulating Akt/GSK-3β and Wnt-4/β-Catenin pathways in male rats

BackgroundDoxorubicin (DOX) drugs used in cancer treatment can cause various adverse effects, including hepatotoxicity. Natural-derived constituents have shown promising effects in alleviating chemotherapy-induced toxicities. This study addressed the effect of Avenanthramides-C (AVN-C) treatment in rats with DOX-indued hepatotoxicity.MethodsAutoDock Vina was used for the molecular docking investigations. In silico toxicity prediction for AVN-C and DOX was performed using the Pro Tox-III server. Four groups of ten male Sprague-Dawley rats were created: Group 1 (Gp1) served as a negative control, Gp2 received an intraperitoneal (i.p.) injection of AVN-C (10 mg/kg), Gp3 received an i.p. dose of DOX (4 mg/kg) weekly for a month, and Gp4 received the same dose of DOX as G3 and AVN-C as G2. Histopathological, molecular, and biochemical analyses were conducted 1 month later.ResultsThe study showed that treatment with AVN-C significantly ameliorated DOX-induced hepatotoxicity in rats by restoring biochemical alterations, boosting antioxidant activity, reducing inflammation, and modulating the Akt/GSK-3β and Wnt-4/β-Catenin signaling pathways in male rats.ConclusionThis study is the first to demonstrate the therapeutic effects of AVN-C therapy on DOX-induced liver damage in male rats. Therefore, AVN-C could have a pronounced palliative effect on the hepatotoxicity caused by DOX treatment. These findings suggest that AVN-C could potentially alleviate the hepatotoxicity associated with DOX-based chemotherapy.

Preparation of gallic acid-loaded chitosan nanoparticles and their chemoprotective effects on N-ethyl-N-nitrosourea-induced hepatotoxicity and mortality in rats.

N-ethyl-N-nitrosourea (ENU) as n-nitrosamine and alkylating agent, ubiquitous within living cells and in the environment can act as a full carcinogen and induce tumor formation in various tissues such as liver. In this study, gallic acid-loaded chitosan nanoparticles (GANPs) were synthesized and evaluated for their chemopreventive effect against ENU-induced hepatotoxicity and mortality in rats. Twenty-four male Wistar rats were divided into four groups including: control, ENU (single doses of 50mg/kg via intraperitoneal injection), GA + ENU and GANPs + ENU. Animals were orally pretreated with GA (50 mg/kg) and GANPs (50 mg/kg) for 30 days, and liver injuries induced by ENU on the 31st day of study. After ENU administration, weight changes and mortality were monitored during 30 days, and then the animals were sacrificed and alpha-fetoprotein (AFP) as a tumor marker, liver function tests (ALT, AST and ALP), oxidative stress markers (GSH and MDA), mitochondrial toxicity parameters, and histopathological assessment were evaluated. Except for AFP and MDA, ENU caused significant elevation of liver enzymes, mitochondrial ROS formation, collapse of mitochondrial membrane potential depletion of GSH, histopathological abnormalities and mortality in rats. Our data showed that GANPs significantly increased the survival of rats by up to 66%, delayed in death time and prevented weight changes after exposure to ENU. Moreover, GANPs restored liver enzyme levels, ROS formation, mitochondrial dysfunction, GSH levels, and histopathological abnormalities towards normal. Our findings suggest that GANPs revealed a significant protective effect against deadly toxicity induced by ENU as an alkylating full carcinogen agent in liver tissue.

Glycerophospholipid metabolic disorders and gender difference of cantharidin-induced hepatotoxicity in rats: Lipidomics and MALDI mass spectrometry imaging analysis

The hepatotoxicity mechanism of cantharidin (CTD), a major active component of Mylabris was explored based on liver lipidome alterations and spatial distributions in female and male rats using lipidomics and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). After oral CTD exposure, the livers of female rats were screened for 104 differential lipids including lysophosphatidylethanolamine(LysoPE)(20:2/0:0) and diacylglycerol(DG)(18:2/22:4), whereas the livers of male rats were screened for 76 differential lipids including fatty acid(FA)(24:6) and DG(18:0/22:4). According to the MALDI-MSI results, female rats exhibited 12 differential lipids with alteration in the abundance and spatial distribution of phosphatylcholine(PC), phosphatidylethanolamine(PE), lysophosphatidylcholine(LysoPC), and LysoPE in the liver lesion area. On the other hand, male rats exhibited 8 differential lipids with changes in the abundance and spatial distribution of PC, PE, and FA in the liver lesion area. The lipidomics- and MALDI-MSI-detected differential lipids strongly disrupted glycerophospholipid metabolism in both female and male rats. Additionally, phosphatidate phosphatase (Lipin1), choline/ethanolamine phosphotransferase 1 (CEPT1), and phosphatidylethanolamine N-methyltransferase (PEMT) were screened to distinguish CTD hepatoxicity in female and male rats. Western blotting analysis demonstrated a significant elevation in Lipin1 expression in female and male rat livers, accompanied by a decrease in PEMT expression. Furthermore, CEPT1 expression increased significantly in female rat livers and decreased significantly in male rat livers. These findings suggested that CTD could disrupt lipid metabolism in a gender-specific manner. Moreover, the combination of lipidomics and MALDI-MSI could offer valuable insights into CTD-induced hepatotoxicity in rats.

Ameliorative Effects of Pomegranate Molasses and Fig on Carbon Tetrachloride Hepatotoxicity in Rats

Ameliorative Effects of Pomegranate Molasses and Fig on Carbon Tetrachloride Hepatotoxicity in Rats

Taurocholic acid represents an earlier and more sensitive biomarker and promotes cholestatic hepatotoxicity in ANIT-treated rats.

Bile acid homeostasis is crucial for the normal physiological functioning of the liver. Disruptions in bile acid profiles are closely linked to the occurrence of cholestatic liver injury. As part of our diagnostic and therapeutic approach, we aimed to investigate the disturbance in bile acid profiles during cholestasis and its correlation with cholestatic liver injury. Before the occurrence of liver injury, alterations in bile acid profiles were detected in both plasma and liver between 8 and 16 h, persisting up to 96 h. TCA, TCDCA, and TUDCA in the plasma, as well as TCA, TUDCA, TCDCA, TDCA, TLCA, and THDCA in the liver, emerged as early sensitive and potential markers for diagnosing ANIT-induced cholestasis at 8-16 h. The distinguishing features of ANIT-induced liver injury were as follows: T-BAs exceeding G-BAs and serum biochemical indicators surpassing free bile acids. Notably, plasma T-BAs, particularly TCA, exhibited higher sensitivity to cholestatic hepatotoxicity compared with serum enzyme activity and liver histopathology. Further investigation revealed that TCA exacerbated ANIT-induced liver injury by elevating liver function enzyme activity, inflammation, and bile duct proliferation and promoting the migration of bile duct epithelial cell. Nevertheless, no morphological changes or alterations in transaminase activity indicative of liver damage were observed in the rats treated with TCA alone. Additionally, there were no changes in bile acid profiles or inflammatory responses under physiological conditions with maintained bile acid homeostasis. In summary, our findings suggest that taurine-conjugated bile acids in both plasma and liver, particularly TCA, can serve as early and sensitive markers for predicting intrahepatic cholestatic drugs and can act as potent exacerbators of cholestatic liver injury progression. However, exogenous TCA does not induce liver injury under physiological conditions where bile acid homeostasis is maintained.

Comparative effect of olive oil and flaxseed oil on drug induced hepatotoxicity in rats.

This study investigates the hepatoprotective effects of olive oil and flaxseed oil on chemically induced hepatotoxicity in rats by evaluating key biochemical parameters, including free fatty acids, iodine value, liver enzymes (ALP, ALT, AST), cholesterol, triglycerides, and HDL levels. The results demonstrated significant improvements in these markers with the administration of olive oil and flaxseed oil, either individually or in combination. The free fatty acid percentages and iodine values were consistent with the known nutritional properties of the oils. Notably, the combination of olive oil and flaxseed oil yielded the most substantial benefits, reducing ALP (115.53 ± 0.44 U/L), ALT (50.77 ± 1.46 U/L), and AST (52.12 ± 0.36 U/L) levels while improving lipid profiles by lowering cholesterol (135.4 ± 1.43 mg/dL) and triglyceride levels (57.14 ± 2.35 mg/dL) and increasing HDL levels (49.20 ± 0.45 mg/dL). These findings suggest that olive oil and flaxseed oil, due to their antioxidant and anti-inflammatory properties, can effectively mitigate liver damage and promote lipid metabolism. The study supports the potential therapeutic application of these oils in managing liver health and preventing hepatotoxicity.

Protective effect of magnetic water against AlCl3-induced hepatotoxicity in rats

This study aimed to examine whether or not aluminum chloride (AlCl3)-induced hepatotoxicity might be mitigated using magnetic water (MW) in rats. This study involved 28 adult male rats randomly assigned into the following 4 groups (7 rats/group): normal control (Cnt), MW, AlCl3, and Al Cl3 + MW. The Cnt group orally received normal saline, the MW group drank MW ad libitum for 2 months, and the AlCl3 and AlCl3 + MW groups were orally administered AlCl3 (40 mg/kg b.w.) alone or in combination with MW for 2 months, respectively. MW reduced AlCl3 toxicity as proved at functional, molecular, and structural levels. Functionally, MW reduced serum levels of liver enzymes (ALT, AST, ALP, GGT), while increased total proteins, and albumin. MW also restored redox balance in the liver (lower MDA levels, higher activities of CAT and SOD enzymes, and upregulated expression of NrF2, HO-1, and GST genes. Molecularly, MW downregulated hepatic expression of the epigenetic (HDAC3), inflammatory (IL1β, TNFα, NFκβ), and endoplasmic reticulum stress (XBP1, BIP, CHOP) genes. Structurally, MW enhanced liver histology. With these results, we could conclude that MW has the potential to ameliorate the hepatotoxic effects of AlCl3 through targeting oxidative stress, inflammation, epigenesis, and endoplasmic reticulum stress.

Histomorphological effects of ß,Ɛ-Carotene-3,3’-diol on the liver following indomethacin-induced hepatotoxicity in adult male Wistar rats

Medicinal plants are globally used as food and in the management of different ailments based on their peculiar phytochemical contents. This study aimed to evaluate the histomorphological effects of ß,Ɛ-Carotene-3,3’-diol on the liver following indomethacin-induced hepatotoxicity in adult male Wistar rats. This is to determine the ameliorative effect of graded doses of ß,Ɛ-Carotene-3,3’-diol. A total of twenty-five adult Wistar rats were randomly divided into five groups (n=5). Liver injury was induced by oral administration of 20 mg/kg b.w of indomethacin after 24 hours fast to animals in groups B-E. Twenty four hours after the induction, animals in groups C-E were given different doses of ß,Ɛ-Carotene-3,3’-diol. At the end of the experimentation, the animals were sacrificed and the livers were collected and fixed for histopathological and histomorphological analyses. The results showed that indomethacin increased the activities of AST, ALT and ALP and also induced histopathological changes. Treatment with ß,Ɛ-Carotene-3,3’-diol was able to attenuate liver injury caused by indomethacin in a dose dependent manner as evidenced in the histoarchitectural changes. This was also corroborated by the histomorphometric analyses. In conclusion, the results suggested the positive influence of ß,Ɛ-Carotene-3,3’-diol in ameliorating liver injury caused by indomethacin and by extension, may be adopted in the management of liver related injury.

Evaluation of Gender-Specific Variation in Lead-Induced Hepatotoxicity in Wistar Rats

Evaluation of Gender-Specific Variation in Lead-Induced Hepatotoxicity in Wistar Rats

Effect of curcumin and cacao extract on interleukin-6 expression on ribociclib-induced hepatotoxicity in rats

Purpose: To assess the relationship between interleukin-6 (IL-6) expression and the protective effect of curcumin and cacao extract on hepatotoxicity caused by ribociclib. Method: Sixty adult male albino rats (9 – 10 weeks old) were utilized in this experiment. The rats were separated into six groups (n = 10 each). Group 1 (control) rats received 2 mL of normal saline daily. Group 2 rats were administered 5 mg/kg ribociclib and group 3 rats received 5 mg/kg ribociclib with a cacao dose of 200 mg/kg daily. Group 4 rats were administered 5 mg/kg ribociclib treated with curcumin (200 mg/kg) daily. Groups 5 and 6 were administered cacao and curcumin doses of 200 mg/kg daily. All rats were sacrificed and liver immunohistochemical and histological examinations were performed. Result: The findings demonstrated that ribociclib administration caused liver damage and morphological changes at a histological level in liver tissue. The immunohistochemical investigation revealed that IL-6 levels were significantly increased in group 2 and control group (p < 0.05). Furthermore, co-administration of curcumin and cacao with ribociclib suppressed the levels of IL-6 expression in the liver tissue of rats compared to control group 1. Conclusion: Co-administration of curcumin and cacao protects the liver against ribociclib-induced liver damage. It is necessary to determine the effect of long-term administration of these extracts on the functions of some organs such as the liver and kidney.

Protective effects of Khaya senegalensis stem bark extracts against acetaminophen-induced oxidative damage, dyslipidaemia, and hepatotoxicity in rats

Background Free radical attacks have been implicated in the aetiology of many diseases and several plants are used traditionally for the management of many oxidative-stress related diseases. Khaya senegalensis is used traditionally for the management diseases such as diabetes and for the treatment of infections. However, mechanisms underlying actions of K. senegalensis are poorly understood. Purpose This study aimed at the preliminary determination of the phytochemical constituents and investigation of the antioxidative and hepatoprotective actions of K. senegalensis in acetaminophen-treated rats. Method Aqueous extracts of K. senegalensis were screened for the presence of key phytochemicals. Total flavonoid and phenolic contents were quantified. Wistar albino rats were pre-treated with saline (control) or graded concentrations of K. senegalensis (50 – 200mg/kgbw) for 10 days prior to acetaminophen (2g/kg body weight) administration. Serum levels of vitamin C, thiobarbituric reactive substances, catalase activities, enzyme markers of liver function were assessed. Cholesterol-phospholipid ratio in treated-rats were determined. Results K. senegalensis extract showed the presence of saponins, tannins, cardiac glycosides, alkaloids, flavonoids and phenolic compounds. Total phenolic and total flavonoid contents were determined as 57.14±0.85mgQE/g and 51.72±0.77mgGE/g. Acetaminophen (2g/kg bw) raised serum TBARS (4.7-fold, P<0.001), H2O2 levels (2.3-fold, P<0.001), AST (5.9-fold, P<0.001), ALT (6.6-fold, P<0.001) and ALP (4.2-fold, P<0.001) and reduced serum levels of vitamin C (54%, P<0.001) and catalase activity (74.6%, P<0.001). Treatment of K. senegalensis extracts inhibited effects of acetaminophen on TBARS (18.2% - 46.4%, P<0.05 – 0.001), vitamin C (1.4 – 1.8-fold, P<0.001 – 0.05), H2O2 levels (19.1 – 50.1%, P<0.001-0.05), catalase activities (1.4 – 3.1-fold, P<0.001 – 0.05), AST (27.7 – 62.8%, P<0.001 – 0.05), ALT (35.6 – 57.5%, P<0.001 – 0.05) and ALP (15.9 – 46.2%, P<0.01 – 0.05). The extract reduced cholesterol-phospholipid ratio (21 – 31%, P<0.05). Conclusion These results motivate further development of the therapeutic potential of K. senegalensis

The effect of Phyllanthus amarus leaf extract on the lipid profile of gentamicin-induced hepatotoxicity in albino rats

Phyllanthus amarus is a medicinal plant, used in traditional practice for treating diseases like hypertension, liver damage and diabetes mellitus. This study aimed to provide a potent therapeutic alternative to conventional drugs in managing liver diseases. Ethanol leaf extract of Phyllanthus amarus at 50, 100 and 200 mg/kg body weight was investigated for its acclaimed hepatoprotective activity in gentamicin-induced hepatotoxicity in albino rats. Thirty albino rats weighing 120-150 g were assigned into six groups (I-VI) of five animals each. Rats in group I (control) received distilled water orally. Rats in groups II, III, IV, V and VI were induced with 100 mg/kg of gentamicin for seven days. Groups III-V were treated with 50, 100 and 200 mg/kg body weight of the extract, respectively while group VI was treated with 200 mg/kg bw of silymarin. The lipid profile that relates to hepatotoxicity was assessed using standard methods. The significantly increased serum and liver lipid profile: cholesterol, triglyceride, Low-density lipoprotein and reduced high-density lipoprotein in the untreated animals were attenuated by the extract. Overall, the extract possesses hepatoprotective activity with 200 mg/kg body weight being the most effective dose. The coronary Heart Index (CRI) was not significantly different from the control. Therefore, the ethanol leaf extract of Phyllanthus amarus could be explored in controlling some of the metabolic dysfunctions usually associated with hepatotoxicity.

SITAGLIPTIN AMELIORATES ATORVASTATIN INDUCED HEPATOTOXICITY IN RATS

Atorvastatin (ATOR) is the most widely used statin for the treatment of hypercholesterolemia, which is the most common cause of severe liver injury. Sitagliptin is a selective dipeptidyl peptidase-4 inhibitor (DPP4-I) used clinically as oral anti-diabetic agent. This study aimed to identify the effect of sitagliptin (SITA) pretreatment against Atorvastatin (ATOR) induced hepatotoxicity in albino rats. Twenty-five rats were divided into five groups (5 rats in each); normal control, ATOR, SITA and two sitagliptin groups, which pretreated with sitagliptin 10 and 20 mg/kg/day in combination with ATOR 20mg /kg / day for eight consecutive days prior to ATOR. The results revealed that ATOR induced noticeable hepatic injury in the form of moderate Hepatoportal + sinusoidal congestion, all Zonal changes, moderate Cloudy swelling + hydropic degeneration, moderate Fatty change and mild Apoptosis. Biochemical analysis exposed a significant rise in the serum transaminases, alkaline phosphatase and lactate dehydrogenase in ATOR group. Increased Proinflammatory TNF-alpha, Oxidative stress MDA and depressed antioxidant system of GSH were evident in ATOR group. On the other hand, sitagliptin pretreatment significantly ameliorated all of the above mentioned biochemical, histopathological changes induced by ATOR. In conclusion, sitagliptin ameliorated the hepatotoxicity induced by atorvastatin. This effect was probably based through suppression of inflammatory, oxidative stress and apoptotic processes. Sitagliptin might exert beneficial effect on diabetic hepatic disorders which mandate further clinical research.

Hepatoprotective effects of ethanol extract of mobe leaves/eeml (artocarpus lacucha buch-ham.) against carbon tetrachloride induced hepatotoxicity in rats

This study evaluates the protective effects of ethanol extract of mobe leaves (Artocarpus lacucha Buch-Ham.) on ALT, AST, and bilirubin levels in rats induced with carbon tetrachloride (CCl4) on Liver. The ethanol extract was prepared by maceration using 96% ethanol. Results showed that administering 400 mg/kg BW of the extract significantly reduced total bilirubin, ALT, and AST levels in CCl4-induced rats. Phytochemical screening revealed bioactive compounds like flavonoids, alkaloids, tannins, saponins, triterpenoids, and glycosides, which are potential antioxidants and hepatoprotective agents. The study concludes that mobe leaf extract has potential as a therapeutic agent to protect the liver from toxic damage. The significant contribution of this research is providing a scientific basis for using mobe leaf extract as a natural hepatoprotective agent, highlighting its potential for safe and effective herbal medicine. Further research and clinical trials are recommended.

Quercetin and Coenzyme Q10: A Comparison study of their Hepatoprotective Effects in Paracetamol-Induced Hepatotoxic Rats

Quercetin and Coenzyme Q10: A Comparison study of their Hepatoprotective Effects in Paracetamol-Induced Hepatotoxic Rats

Assessment of the Ameliorative Potential of Water-Based Leaf Extracts from Talinum triangulare, Vernonia amygdalina, and Ocimum gratissimum on Liver Damage Caused by Dichlorvos in male wistar Rats

The increasing human exposure to dichlorvos (DDVP) and its toxicity is a growing public health concern. This work was aimed at studying the therapeutic effect of Vernonia amygdalina, Ocimum gratissimum, Talinum triangulare extracts against DDVP induced hepatotoxicity in rats. Total of 50 male adult rats of average weight 272g were placed in ten groups (n=5) and orally administered normal saline (normal control), 8.0mg/kg body weight DDVP (positive control), 8.0mg/kg body weight DDVP + 200mg/kg and 400mg/kg body weight of the plant extracts and 20 mg/kg body weight and 40 mg/kg bodyweight of vitamin C for 28 days. DDVP significantly (P<0.05) increased Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP) and Gamma glutamyl transferase (GGT) when compared with normal control. Treatment with aqueous leaf extracts of Vernonia amygdalina, Ocimum gratissimum, Talinum triangulare significantly reversed the distortions in the values of biochemical parameters when compared with positive control. Photomicrographs obtained from histological examination of liver tissues corroborate these findings. Aqueous leaf extracts of Vernonia amygdalina, Ocimum gratissimum, Talinum triangulare may have therapeutic potentials to DDVP induced hepatotoxicity in rats.

Biochemical Studies on Efficiency of Natural Gum in Chronic Kidney Failure and Liver Cirrhosis in Rats

It is well-established that apoptosis, oxidative stress, and inflammation are associated with several disorders, including chronic renal disease and hepatic disease. Oxidative stress (OS) is a major cause of death from end-stage renal disease which also contributes to atherosclerosis and cardiac issues. The present study aimed to assess the efficacy of Gum Arabic (GA) in mitigating renal damage and hepatotoxicity in rats induced by Chloropyrifos-methyl (CPM). A total of 42 male Wistar rats were divided into seven groups, with four groups (group 2 [IC], group 5 [GA1+IC]a, group 6 [GA2+IC], and group 7 [GA1+IC]b treated with CPM for eight weeks to induce hepatic and renal damage. Two models of GA administration, including the standard oral model in drinking water (15% w/v) and the oral model by gavage at a dose of 1 g/kg body weight were administered. Physiological parameters of kidney and liver functions, including urea, creatinine, AST, and ALT along with anti-oxidant factors (Melaodialdehyde, superoxide dismutase, reduced glutathione, and catalase) were measured in plasma, and homogenates of renal and hepatic tissues on day 57 of the experiment. In addition, histopathological examination was conducted on liver and kidney tissues using hematoxylin and eosin stain to evaluate the efficacy of GA on damaged tissues. Gum Arabic was found to significantly reduce CPM toxic effects in the liver and kidney in groups treated with CPM as liver and kidney parameters were reduced to normal levels. Furthermore, GA reduced histological indicators of inflammation, fibrosis, and apoptosis, as well as renal morphological damage. Additionally, it reduced OS in liver and kidney homogenates. In conclusion, GA effectively reduced the damage that CPM inflicted on liver and kidney tissue by stabilizing physiological parameters to normal levels and repairing cellular structures damaged by OS. Keywords: Antioxidant, Anti-inflammatory, Gum Arabic, Kidney, Liver, Oxidative stress

The protective effects of esculetin against Doxorubicin‐Induced hepatotoxicity in rats: Insights into the modulation of Caspase, FOXOs, and heat shock protein pathways

AbstractDoxorubicin (DOX) is an anthracycline antibiotic widely employed to treat carcinoma. Nevertheless, severe cardiotoxic side effects restrict its clinical use. Esculetin, a natural flavonoid, is found abundantly in plants. This study evaluated the protective effects of esculetin against DOX‐induced hepatotoxicity in rat livers. Forty‐eight rats were randomly divided into six groups with eight rats in each group: control (I), DOX (II), esculetin (III, 50 mg/kg), esculetin (IV, 100 mg/kg), DOX+esculetin 50 (V, DOX+esculetin 50 mg/kg), and DOX+esculetin 100 (VI, DOX+esculetin 100 mg/kg). The administration of esculetin effectively mitigated alterations in the measured biochemical parameters induced by DOX. Gene expression analyses demonstrated that esculetin treatment significantly reduced the DOX‐induced expression of Foxo1, Hspa1a, Hsp4a, Hsp5a, Casp3, and Casp9 while increasing the DOX‐induced expression of Foxo3. These findings suggest that esculetin, with its antioxidant and anti‐inflammatory effects, might be a therapeutic option for protecting against DOX‐induced hepatotoxicity.

An Assessment of Hepato-protective Activity of Hygrophila auriculata Root Extract against Hepatic Injured Rodent Model

Liver is a crucial organ that is susceptible to several hepatotoxins causing hepato-toxicities. These days, medicinal plants have been considered to be more promising compared with the conventionally utilized medications for hepatic treatments. In light of the dire circumstances affecting worldwide currently, Hygrophila auriculata is a vital plant with an abundance of health advantages and hepatoprotective properties. In this experiment, carbon tetrachloride (CCl4) was utilized to cause hepatotoxicity in rats and this plant's anti-hepatotoxic activity was evaluated through assessing the outcomes of several parameters (Liver functioning tests, kidney functioning tests and lipid profiles). Subsequent research revealed that the plant may, to varying degrees and in a dependent way, successfully restore the disrupted pathological state to healthy status. To interpret statistical analysis, the "One-way Anova test" was conducted using the SPSS 16 software. In the case of SGPT, the medium and high dose produced statistically significant (p<0.05) outcomes as compared to the negative control group and for SGOT decrease in all three groups were non-significant (p>0.05). Then for creatinine levels, the outcome for medium, and high dosages were statistically significant (p<0.05) whereas in case of urea level only the high dose imparted significant (p<0.05) decrease. However, none of the dosages for total cholesterol and triglyceride level produced statistically significant (p<0.05) effects. Only in the medium and high doses, HDL levels improved statistically significantly (p<0.05) whereas only the high dosages reduced reduce the LDL quantity in the blood significantly (p<0.05). As a result, Hygrophila auriculata is thought to possess a significant capacity for liver protection and may serve as a more secure and effective substitute for the commercially available synthetic medication, silymarin. To sum up, additional research is required in the future before this appealing plant could get utilized in the arena of hepatotoxic treatments.