Liver Toxicity In Rats Research Articles

Sophoricoside reduces inflammation in type II collagen-induced arthritis by downregulating NLRP3 signaling

Immune responses, especially NLRP3 signaling in macrophages, play critical roles in rheumatoid arthritis (RA), an autoimmune and inflammatory disease. In this study, we aimed to identify novel therapies for RA. We focused on sophoricoside (SOP), an isoflavone glycoside isolated from Sophora japonica. We predicted the targets of SOP and performed a Gene Ontology analysis to assess its effects. The results suggested that SOP is related to inflammation regulation. We verified these findings by performing in vitro experiments with M1 macrophages differentiated from human peripheral blood monocytes (THP-1 cells). Sophoricoside administration reduced inflammatory activity and NLRP3, Caspase-1, and IL-1β protein levels in macrophages. In addition, SOP and triptolide (TP) was administered intragastrically to male SD rats (n = 40) in a collagen-induced arthritis model. We observed that SOP and TP reduced the inflammatory responses and symptoms of RA. Moreover, unlike TP, SOP showed no liver or kidney toxicity in rats. In conclusion, SOP reduces inflammation in type II collagen-induced arthritis by downregulating NLRP3 signaling and has potential for future clinical applications as an ideal therapy for RA.

Inhibitory activity of nanoencapsulated quercetin against sodium arsenite-induced sub-acute liver toxicity in rats

Arsenic, a metalloid toxicant, is associated with a major global health problem as oxidative stress, a prime cause of tissue toxicity. The subject of our investigation was to assess the therapeutic efficiency of nanoencapsulated quercetin (QC) in combating sodium arsenite (NaAsO2)-inducted sub-acute hepatocellular toxicity in rat model. The rats of the hepatic damage group were injected subcutaneously (s.c.) four dosages of NaAsO2 (92.36 µM/kg b.wt.) twice a week. The rats of the polylactide nanoencapsulated QC group were injected intravenously (i.v.) four doses of nanoencapsulated QC (8.97 µmol/kg b.wt.) twice a week 2 h after the treatment (s.c.) with 92.36 µM /kg b. wt. NaAsO2 twice a week for four doses. The rats of the empty nanocasule or free QC treated group were injected i.v. four doses empty nanocapsule or free QC twice a week 2 h after the treatment (s.c.) with same doses of NaAsO2 twice a week for four doses. Arsenic deposition (580±20 µg/g protein) observed in liver tissue of rats treated with arsenite (92.36 µM/kg b.wt.), was found to reduce (120±9 µg/g protein) by the treatment of nanoencapsulated QC in rats significantly (p<0.001). The levels of antioxidant enzymes and GSSG/GSH ratio enhanced (p<0.001/0.1/0.01) by the treatment of NaAsO2 were reduced by the post treatment of nanoencapsulated QC significantly (p<0.001/0.01). The levels of ROS, lipohydroperoxide or membrane microviscosity increased or decreased (p<0.001) by the treatment of NaAsO2 were monitored to reduce or enhance significantly (p<0.001) by the treatment of nanoencapsulated QC in rat liver respectively. The blood serum biochemical levels enhanced (p<0.001) by the treatment of NaAsO2 were found to reduce significantly (p<0.001) by the treatment of nanoencapsulated QC in rats. The TGFβ1 and MMP-13 in the rat plasma augmented (p<0.001) by the treatment of NaAsO2-exposure were found to decline (p<0.001) significantly by the treatment of nanoencapsulated QC in rats. The rats in the other groups such as empty nanocapsule or free QC treated showed no or less inhibitory efficiency against NaAsO2-treatment compared to nanoencapsulated QC treated group. Application of nanoencapsulated QC may be a potent formulation to get higher inhibitory therapeutic efficiency against NaAsO2-induced sub-acute hepatocellular toxicity.

Assessment of sweet whey fortified with Bifidobacteria and selenium on reduction of pesticide liver toxicity in albino rats

Deltamethrin (DLM) represents one of the most commonly used pesticides. It passes through milk, vegetables, and fruits to humans or through animals (veterinary drugs and feeding on contaminated forage) to milk; it can escape from skin to blood and be secreted in breast milk in lactating women. It is believed to have neurotoxic, nephrotoxic, and hepatotoxic properties. To investigate deltamethrin-induced hepatotoxicity, 64 rats were divided into eight groups. The control group did not receive any treatment. The groups were as follows: D 30 mg DLM/kg body weight (BW) dissolved in corn oil; B 1 mL whey (1010 cfu/mL of Bifidobacterium longum ATCC 15707); S 1 mL whey (0.5 ppm selenium); BS 1 mL whey (1010 cfu/mL of B. longum ATCC 15707 + 0.5 ppm selenium); BD 1 mL whey (1010 cfu/mL of B. longum ATCC 15707 + DLM); SD 1 mL whey (0.5 ppm selenium) + DLM; and BSD 1 mL whey (1010 cfu/mL of B. longum ATCC 15707) + 0.5 ppm selenium + DLM. Results revealed that the manipulation of Bifidobacteria with selenium triggered a significant improvement in AST (U/mL), ALT (U/mL), GSH (mg/g), TNF-α (pg/mL), NF-κB (ng/mL), and BCL2 (ng/mL) from 166.7 ± 6.42, 30.67 ± 0.55, 0.252 ± 0.005, 17.18 ± 0.42, 1.14 ± 0.10, and 1.77 ± 0.06 versus 334.9 ± 4.7, 72.83 ± 2.49, 0.108 ± 0.005, 33.57 ± 0.59, 2.58 ± 0.05, and 1.04 ± 0.04, respectively, compared to DLM group. As well as reduction in histopathological necrosis, congestion, and degradation. Whey beverages fortified with B. longum and selenium implicated a reduction in oxidative stress and histopathological degradation that accomplished DLM toxicity. The utilization of whey (a byproduct of cheese making) is considered a recycling process that supports eco-friendly practices and sustainability, thus encouraging its use as a protective tool in animal feed or manipulation by humans, especially workers in pesticide plants.

Hepatoprotective activity of aqueous <i>Curcuma longa</i> rhizome extract against carbon tetrachloride-induced liver toxicity in adult Wistar rats

Hepatoprotective activity of aqueous <i>Curcuma longa</i> rhizome extract against carbon tetrachloride-induced liver toxicity in adult Wistar rats

Hepatoprotective effects of resveratrol on α-amanitin-induced liver toxicity in rats

ObjectiveThe hepatoprotective effects of resveratrol against α-Amanitin (α-AMA)-induced liver toxicity were investigated in an experimental rat model, focusing on oxidative stress, inflammation, apoptosis, and liver function. MethodsThirty-two male Sprague-Dawley rats were divided into four groups (n = 8 per group): Control, resveratrol, α-AMA, and resveratrol+α-AMA. The resveratrol group received 20 mg/kg resveratrol orally for 7 days. The α-AMA group received 3 mg/kg α-AMA intraperitoneally on the 8th day. The resveratrol+α-AMA group received 20 mg/kg resveratrol orally (7 days) followed by 3 mg/kg α-AMA intraperitoneally on the 8th day. Liver tissues and blood samples were collected 48 h after α-amanitin administration for histopathological, immunohistochemical (NFkB, LC3B), and biochemical analyses (GSH, MDA, CAT, GPx, MPO, NOS, AST, ALT). Resultsα-AMA significantly increased AST and ALT levels, oxidative stress marker (MDA), and inflammatory marker (MPO), while reducing antioxidant levels (GSH, CAT, GPx) and NOS concentration (P < 0.001 for all parameters). Histopathological analysis showed severe liver damage with increased NFkB and LC3B expression. resveratrol treatment significantly reduced AST and ALT levels (P < 0.01 for both parameters), decreased MDA and MPO levels, and increased NOS concentration, GSH, CAT, and GPx levels (P < 0.05 for all parameters). Reduced NFkB and LC3B expression in the resveratrol+α-AMA group and showed histopathological improvements. ConclusionResveratrol demonstrated substantial hepatoprotective effects against α-AMA induced liver toxicity by reducing oxidative stress, inflammation, and apoptosis, and improving liver function. These findings suggest that resveratrol could be a potential therapeutic agent for treating liver damage caused by potent hepatotoxins like α-AMA.

Pharmacotherapeutic potential of malvidin to cure imidacloprid induced hepatotoxicity via regulating PI3K/AKT, Nrf-2/Keap-1 and NF-κB pathway

Imidacloprid (IMI) is one of the top-notch insecticides that adversely affects the body organs including the liver. Malvidin (MAL) is a natural flavonoid which exhibits a wide range of pharmacological properties. This research was designed to evaluate the protective ability of MAL to counteract IMI instigated liver toxicity in rats. Thirty-two rats were divided into four groups including control, IMI (5mg/kg), IMI (5mg/kg) + MAL (10mg/kg) and MAL (10mg/kg) alone treated group. The recommended dosages were administrated through oral gavage for 4 weeks. It was revealed that IMI intoxication disrupted the PI3K/AKT and Nrf-2/Keap-1 pathway. Furthermore, the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), heme-oxygenase-1 (OH-1) and glutathione reductase (GSR) were reduced while upregulating reactive oxygen species (ROS) and malondialdehyde (MDA) levels after IMI treatment. Moreover, IMI poisoning increased the levels of ALT (Alanine aminotransferase), AST (Aspartate transaminase), and ALP (Alkaline phosphatase) while reducing the levels of total proteins and albumin in hepatic tissues of rats. Besides, IMI administration escalated the expressions of Bcl-2-associated protein x (Bax) and cysteine–aspartic acid protease-3 (Caspase-3) while downregulating the expressions of B-cell lymphoma 2 (Bcl-2). Similarly, IMI intoxication, increased the levels of Interleukin-6 (IL-6), Nuclear factor kappa-B (NF-κB), Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and the activity of cyclooxygenase-2 (COX-2). Furthermore, IMI disrupted the normal architecture of hepatic tissues. However, MAL treatment remarkably protected the liver tissues via regulating abovementioned disruptions.

DETERMINATION OF ANTIOXIDANT ACTIVITY OF HIPPOPHAE RHAMNOIDES L. GROWING IN TURKEY AND INVESTIGATION OF ITS EFFECTS ON THE LIVER TOXICITY IN RATS

Objective: The goal of the present work was to investigate the antioxidant properties of the extracts of Hippophae rhamnoides L. and to determine their effects on liver toxicity in rats. Material and Method: Metal chelation, reducing power and DPPH radical scavenging methods were used in the antioxidant activity analysis of extracts. The total phenolic content was determined using the folin-ciocalteu reagent. Plant extracts were administered orally to the rats at doses of 500 µg/kg for 2 days. Each animal group was composed of six female Albino Wistar rats with an average weight of 250 g. Microscopic examination was carried out to observe any pathological changes in the rat livers. Result and Discussion: Water extract showed the highest radical scavenging activity (48.65%), reducing power (0.291 absorbance at 700 nm) and metal chelating (35.40%) at 1 mg/ml concentration. Histopathological studies showed that especially water extract reduced the severity of CCl4-induced intoxication. Hippophae rhamnoides L. extracts were found to have antioxidant activity, and also Hippophae rhamnoides L. water extract was shown to be particularly effective in preventing liver damage.

The Potential Effects of Cake Fortified with Date Seeds against Aflatoxin B1-Induced Liver Toxicity in Rats

The Potential Effects of Cake Fortified with Date Seeds against Aflatoxin B1-Induced Liver Toxicity in Rats

Therapeutic potential of salvigenin to combat atrazine induced liver toxicity in rats via regulating Nrf-2/Keap-1 and NF-κB pathway

Atrazine (ATR) is the second most extensively used herbicide which adversely affects the body organs including liver. Salvigenin (SGN) is a flavonoid which demonstrates a wide range of biological and pharmacological abilities. This study was planned to assess the protective ability of SGN to avert ATR induced liver damage in rats. Thirty-two rats (Rattus norvegicus) were divided into four groups including control, ATR (5 mg/kg), ATR (5 mg/kg) + SGN (10 mg/kg) and SGN (10 mg/kg) alone supplemented group. ATR exposure reduced the expression of Nrf-2 while instigating an upregulation in Keap-1 expression. Furthermore, the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), heme‑oxygenase-1 (HO-1) and glutathione reductase (GSR) contents were decreased while increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels after ATR treatment. Moreover, ATR poisoning increased the levels of ALT, AST, and ALP while reducing the levels of total proteins, and albumin in hepatic tissues of rats. Besides, ATR administration escalated the expressions of Bax and Caspase-3 while inducing a downregulation in the expressions of Bcl-2. Similarly, ATR intoxication increased the levels of Interleukin-6 (IL-6), Nuclear factor kappa-B (NF-κB), Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and the activity of cyclooxygenase-2 (COX-2). Furthermore, ATR disrupted the normal histology of hepatic tissues. However, SGN treatment remarkably protected the liver tissues via regulating antioxidant, anti, inflammatory, anti-apoptotic as well as histology parameters. Therefore, it is concluded that SGN can be used as therapeutic agent to combat ATR-induced hepatotoxicity.

Protective effects of cupressuflavone against doxorubicin-induced hepatic damage in rats

Doxorubicin (DOX) is a potent chemotherapeutic agent that is used in various sorts of malignancies. However, its uses are restricted owing to its deleterious effects on different organs including the liver. Cupressuflavone (CUP) is a plant-based flavonoid which is well known for its biological as well pharmacological potential. Our investigation aimed to evaluate the ameliorative potential of CUP against DOX provoked liver toxicity in rats. Twenty-four albino rats (Rattus norvegicus) were distributed into four distinct groups such as control, DOX (3 mg/kg), co- administrated DOX (3 mg/kg) + CUP (40 mg/kg) and CUP (40 mg/kg) only. DOX exposure reduced catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), Glutathione reductase (GSR), glutathione-S-transferase (GST) activities and glutathione (GSH) content while escalating the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Besides, the levels of ALT, AST and ALP were increased in response to DOX exposure. Furthermore, administration of DOX upregulated the levels of Interleukin-6 (IL-6), Nuclear factor kappa-B (NF-κB), Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and the activity of cyclooxygenase-2 (COX-2). The treatment of DOX reduced the levels of Bcl-2 while escalating the levels of Caspase-3, Caspase-9 and Bax. Similarly, DOX intoxication instigated various histopathological disruptions in hepatic tissues of rats. However, supplementation of CUP notably (p < 0.05) restored abovementioned hepatic dysregulations owing to its anti-oxidative, anti-inflammatory as well as anti-apoptotic potential. Our results manifested that CUP could be used as hepatoprotective agent againt DOX induced liver damage in rats.

Biochemical, morphological and molecular assessments of n butanol fraction of Phoenix dactylifera L. following exposure to inorganic mercury on the liver of Wistar rats

BackgroundMercury chloride (HgCl2) damages tissues it comes in contact with in sufficient concentration. This study evaluated the protective effects of n-butanol fraction of Phoenix dactylifera (BFPD) on mercury-triggered liver toxicity in Wistar rats. 25 male rats were divided into 5 groups of 5 rats each. Group I was administered 2 ml/kg of distilled water; group II was administered 5 mg/kg of HgCl2; group III was administered 500 mg/kg of BFPD + 5 mg/kg of HgCl2; group IV was administered 1000 mg/kg of BFPD + 5 mg/kg of HgCl2, while group V was administered 100 mg/kg of silymarin + 5 mg/kg of HgCl2. orally for 2 weeks. The rats were euthanized and liver tissue blood samples were collected for histological, histochemical, stereological, immunohistochemical, molecular, and biochemical studies.ResultsThe results revealed that HgCl2 induced oxidative stress in the rats evident by histoarchitectural distortions and altered levels of liver enzymes, proteins, and oxidative stress biomarkers when compared to the control. However, BFPD treatment restored these changes. Glutathione peroxidase levels decreased (p < 0.05) in the HgCl2−treated group when compared to the control and BFPD-treated groups. HgCl2 group revealed reduced reactivity with histochemical and immunohistochemical stains (Masson’s Trichrome and B cell Lymphoma 2) when compared to the control, with a significant decrease in quantified liver Bcl-2 stain intensity when compared to the silymarin-treated group. BFPD administration revealed normal staining intensity comparable to the control. HgCl2 administration revealed a remarked decrease in the number of hepatocytes when compared to the control, BFPD, and silymarin groups. BFPD preserved (p < 0.05) the stereological features when compared to the HgCl2-treated group. GPx activity in the liver decreased (p < 0.05) with HgCl2 administration when compared to the control and silymarin-treated groups. BFPD attenuated GPx gene activity to levels similar to the control indicating some level of amelioration against HgCl2-induced toxicity.ConclusionsThe ability of BFPD to mitigate HgCl2 triggered liver alterations could be attributed to the antioxidant property of its flavonoid content. Therefore, BFPD may be a potential candidate for treating and managing liver-induced mercury intoxication.

Hepato-protective Effect of Costus afer (Okpete) Juice Extract on Alcohol-induced Liver Toxicity in Adult Female Wistar Rats

Background: The oral intake of alcohol has become a widespread concern due to its high risk to body health. Therefore, our purpose in this study was to reveal the antioxidant efficacies of natural Costus's afer stem juice extract on hepatotoxicity induced by ethanol in adult female wistar rats. Methods: We examined the impacts of liver toxicity, were the experimental animals were given 1ml of 10% ethanol daily for 21 days, thereafter, C. afer was administered to evaluate its ameliorative effect in the female albino wistar rats orally treated with C. afer juice extract (200 and 400 mg/kg) for 7days. The rats were divided into four (4) groups; Group A served as the control group, which was given rat chow and water only. Groups B, C and D were given 1ml of 10% ethanol. Afterwards, groups C and D were treated with 200 and 400 mg/kg using 1ml and 2ml of the juice extract of C. afer, respectively. A liver function test and histological analysis were carried out. Results: The results showed that treatment with C. afer after the oral consumption of ethanol caused elevation in serum liver function parameters (alanine transferases, aspartate transaminase, and alkaline phosphate), which is significant compared to the control group. There was also a slight restoration in histopathological changes in the liver, as revealed by decreased areas of inflammation. Conclusion: The therapeutic efficiency of C. afer juice extract could be due to traces of anti-inflammatory properties and the ROS-scavenging agent. Our findings prove that the elevation of liver function markers by C. afer enables hepatic tissue to suppress inflammatory and oxidative mechanisms, resulting in enhanced liver structure and function. Therefore, C. afer extract is a protective and therapeutic supplement against toxic agents.

Metabolic profiling of Verbena bonariensis L. extract by LC/MS and evaluation of the hepatoprotective potential with isoniazid- and rifampicin-induced hepatotoxicity in rats.

The study explored the hepatoprotective activity and metabolic profile of Verbena bonariensis L. methanol extract (VBM) and fractions using isoniazid as well as rifampicin-triggered liver toxicity in Wistar albino rats. Metabolite profiling of VBM using HPLC-PDA-ESI-MS identified 12 compounds, mainly iridoids, phenylpropanoids, and flavonoids, where verbascoside represents the major compound. Different biochemical parameters such as aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP), bilirubin, and total protein levels were used to assess liver functions. All the evaluated samples exhibited hepatoprotective potential, but VBM exhibited maximum activity and a notable decline in ALP (p < 0.05, significant), even better than the standard drug (silymarin). VBM significantly reduced the elevated ALT, AST, ALP, and total bilirubin. It also triggered a significant elevation in total proteins compared with diseased animals. This was further consolidated by histopathological studies. Verbena bonariensis L. could serve as a potent hepatoprotective agent and may alleviate liver ailments.

Effects of Buccholzia coriacea (wonderful kola) on hepatoprotective, nephrotective and oxidative stress of aluminium chloride induced wistar rats

Buchholzia coriacea seeds has been reported to have various medicinal properties. This study evaluates the effect of the aqueous extract of Buchholzia coriacea seed (wonderful kola), on Aluminium chloride induced liver toxicity in adult male Wistar rats. 24 rats weighing between 150 g - 210 g were divided into five groups. Group A- (the control group) received water and animal chow. Group B received 200mg/kg of AlCl3 only, Group C received aluminum chloride and vitamin C for 14 days. Group D received 250 mg/kg body weight body weight (Low Dose) of aqueous extract Buchholzia coriacea and (200 mg/kg) AlCl3. Group E received 1000mg/kg body weight (High Dose) of aqueous extract of Buchholziacoriacea and (250mg/kg) AlCl3. The animals were sacrificed, the liver and kidney was excised and processed for routine paraffin sections at 5micromes thick. Sections were stained with Haematoxylin and Eosin to demonstrate histoarchitecture. Biochemical analysis was also carried out to determine the effects on liver and kidney antioxidant enzymes. Histological assessment showed narrowed central vein, degeneration of hepatocytes and distortion of sinusoids in the AlCl3 alone treated groups. The histoarchitecture of the liver in the other groups showed improvement especially in Group E (High Dose of B. coriacea) and Group C (vitamin C and aluminum chloride only). The biochemical analysis on the other hand showed significantly reduced activities in GSH, SOD, CAT and significantly increased level of MDA in the AlCl3 only group. In the other groups, MDA levels reduced, GSH, SOD and CAT also increased enzymatic activities following the administration of B. coriacea. The study concludes that Buchholziacoriacea seed extract plays a role in protecting liver and kidney from AlCl3 toxicity.

Protective effects of jervine purified from Veratrum album on paracetamol-induced liver toxicity in rats

Purpose: Since paracetamol toxicity is a very common type of poisoning, we planned to investigate whether Jervine has an effect on paracetamol toxicity by utilizing its anti-inflammatory effect.&#x0D; Materials and Methods: In our study, 42 Sprague Dawley rats of 8 weeks of age were used. Seven groups were formed with 6 animals in each group. At the 24th hour of the study, all groups underwent laparotomy under anesthesia, and liver dissection was performed. Hematoxylin and Eosin (H&amp;E) staining was performed to evaluate liver histopathology. SOD, CAT, GSH, and MDA levels were analyzed biochemically.&#x0D; Results: Histopathological, while liver tissues were normal in the control group, we observed degeneration areas, inflammation, and hemorrhage in the paracetamol group. Jervine reduced the severity of paracetamol toxicity and prevented liver damage. Jervine significantly increased SOD levels. Paracetamol administration significantly decreased CAT levels. Paracetamol significantly decreased GSH levels compared to the control group. &#x0D; Conclusion: Jervine reduced the adverse effects of paracetamol toxicity on liver tissue, such as degeneration, inflammation, and hemorrhage. Jervine increased antioxidant activity and reduced the harmful effects of NAPQI, the toxic metabolite of paracetamol, on liver tissue.

Effect of Ethanolic Stem Extract of Nelsonia Canescens on Selected Biochemical Parameters in Male Wistar Rats Induced with Sodium Arsenite

Medicinal plants are those that have curative qualities or have positive pharmacological effects on the human body. The effect of ethanolic stem extracts from Nelsonia canescens was studied in relation to Sodium arsenite-induced toxicity in wistar rats. Fresh stem extract of Nelsonia canescens were obtained behind rice mill area, Wukari, Taraba state and was shade dried at room temperature and was homogenized into powder and measured at 300g into 100ml of absolute ethanol for 72 hours. 15 healthy male rats of 70g to 90g weight were obtained from animal house Makurdi, Benue state. Animals from Group 1 were used as control. 5mg/kg body weight of Sodium arsenite was administered to Group 2 animals while animals in Groups 3, 4 and 5 were administered with Nelsonia canescens ethanolic stem extracts 50 mg/kg, 100mg/kg and 200 mg/kg as well. At the end of 3 weeks the animals were sacrificed and serum sample were collected and analysed using standard methods. The results indicate that, when compared to those who received Sodium arsenite, those who received ethanol stem extracts of Nelsonia canescens showed a comparatively considerable liver protection against Sodium arsenite -induced damage. The levels of biochemical parameters: Albumin, Total protein, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), Total bilirubin, Urea, Creatinine of rats administered with Sodium arsenite only was also observed. The Nelsonia canescens extract’s activity at 200mg/kg bw (higher dose) give a reasonable decrease in the amount of these liver enzymes. Deducing from study results, it indicates that Nelsonia canescens leaf extracts could be an effective agent in Sodium arsenite mediated liver toxicity in adult wistar rats and drug development.

Grape seed extract prevents chlorpyrifos-induced toxicity in rat liver through the modulation of phase I detoxification pathway.

Chlorpyrifos (CPF) poisoning is a public health problem for which there is not currently any effective prophylaxis. In this study, we investigated the protective effect of grape seed extract (GSE) against CPF-induced hepatotoxicity. Rats were daily treated either with CPF (2mg/kg) or CPF and GSE (20mg/kg) for 1week, sacrificed, and their livers dissected for biochemical, molecular, and histopathological analyses. CPF generated liver dysfunction by altering carbohydrate, lipid, amino acid, ammonia and urea metabolism, and provoked mitochondrial impairment through disturbing tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), and mitochondrial viability. CPF also induced cholinergic excitotoxicity along with oxidative stress and histopathological alterations. Interestingly, treatment with GSE prevented all the detrimental effects of CPF through the regulation of cytochrome P450 (CYP450) gene expression. Molecular docking analysis indicated that GSE-containing polyphenols acted as epigenetic modulators through inhibiting DNA (cytosine-5)-methyltransferase 1 (DNMT1), thus favoring the CYP2C6 detoxification pathway. Thereby, GSE might be a promising strategy in the protection of the liver against CPF toxicity.

The Protective Effect of Roflumilast Against Acute Hepatotoxicity Caused by Methotrexate in Wistar Rats: In vivo Evaluation.

Methotrexate (MTX) is one of the most widely used drugs in cancer chemotherapy and treating rheumatoid arthritis. The hepatotoxicity of MTX is one of its major side effects. Roflumilast (ROF) has been recognized to have antioxidant and anti-inflammatory activity in in-vivo and in-vitro models. The present study aimed to explore the potential protective effects of roflumilast against MTX-induced liver toxicity in male Wistar rats. High dose of 5 mg/kg for 4 consecutive days subcutaneous (S.C) injection of methotrexate for induction of acute liver injury. A total of 24 Wistar rats, rats were used in four different groups. The NS injections were given S.C to the control group once a day for 4 consecutive days. SC injections of MTX (5 mg/kg) were given to the MTX group daily for four days. At 5 mg/kg once daily for four days, the roflumilast group was given daily oral roflumilast. An injection of MTX and oral roflumilast were given to the MTX + roflumilast group once daily for four consecutive days. Administration of high dose MTX (5 mg/kg) today 4 produced a significant decrease in hepatic glutathione (GSH) levels and a significant increase in ALT and AST liver enzymes, hepatic malondialdehyde (MDA), tumor suppressor protein (p53), interleukin 6, interleukin 1 levels compared to the control group. Treatment with roflumilast for 4 days significantly attenuated unfavorable changes in these parameters. According to histopathological findings, Roflumilast significantly reduced MTX-induced inflammation and degeneration in the liver. In conclusion, the findings indicate that roflumilast may have a potential therapeutic benefit in treating rats with MTX-induced liver toxicity by mitigating its effects. The aim of this study is to investigate the potential protective effects of roflumilast against MTX-induced liver toxicity in Wistar rats.

Assessment of Liver Toxicity in Wistar Rats after Chronic Exposure to Phosphate-Processing Wastewaters from Gafsa-Metlaoui Laundry in Tunisia

In the mining basin of the Gafsa region in southwestern Tunisia, environmental exposure to randomly discharged phosphate-processing wastewaters (PPWW) presents a serious threat to health and the surrounding ecosystems. Thus, the contaminated areas are in continuous deterioration over time. There is a paucity of information on the deleterious effects of this kind of effluent. In the current work, the PPWW characterization showed the presence of high contents of Pb (0.90 ± 0.02 mg/L), Cd (0.35 ± 0.27 mg/L), Cr (0.43 ± 0.1 mg/L) and Fe (215.1 ± 2.41 mg/L), exceeding the permissible limits. To assess the chronic toxicity of the effluent in mammalians, two doses of PPWW (50% and 100%) were administered by gavage to Wistar rats for 28 consecutive days. The results revealed that the two PPWW concentrations significantly increased the plasma biochemical markers (bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH)), compared to untreated animals. Moreover, PPWW treatment severely altered the lipid profile by increasing the contents of triglycerides, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-cholesterol) by 143%, 114%, and 91%, respectively, and significantly reduced the high-density lipoprotein cholesterol (HDL-cholesterol) level by 46%, compared to the control animals. In addition to the significant decrease in activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the liver of intoxicated rats, the malondialdehyde (MDA) level was remarkably altered. All of these were associated with deep histopathological damages, materialized by dilatation of sinusoids, congestion of the centrilobular vein, and inflammatory cell infiltration. These disturbances were accompanied by metal detection in the liver and blood. Additionally, DNA fragmentation detected in hepatic tissues highlighted the genotoxic effects of PPWW. All of the aforementioned effects occurred in a PPWW dose-dependent manner. These findings evidenced, for the first time, the in vivo-deleterious impacts of this type of effluent on mammalians inhabiting the mining basin area and therefore showed the real threats to which humans, as consumers, could be exposed. Accordingly, there is a dire need to pay special attention to PPWW before being discharged into environmental ecosystems without any prior treatments.

Liver toxicity in rats after subchronic exposure to HTP aerosol and cigarette smoke.

Heated tobacco product (HTP) considered to be a novel tobacco product which was reported safer than traditional cigarettes evidenced by lower potential harmful components released. Liver is an important detoxification organ of the body, the chemical components in aerosols are metabolized in the liver after absorbed, so it is necessary to explore the effect of HTP on the liver. The potential effect of HTP and cigarette smoke (CS) on SD rats was explored according to OECD 413 subchronic inhalation. The rats were randomly divided into Sham (air), different dosage of HTP groups (HTP_10, 23 and 50μg nicotine/L aerosol) and Cig_23 (23μg nicotine/L aerosol) group. After exposure, the clinical pathology, inflammation and oxidative stress were measured. The clinical pathology results showed that both HTP_50 and Cig_23 led to abnormality of ALT for male rats. CS and HTP exposure reduced the expression of IL-1β, IL-6 and TNF-α and mitochondrial medicated oxidative stress. In addition, the ATP production was reduced in Cig_23 group. Although inflammation and oxidative stress were displayed, no apoptosis were observed by TUNEL assay and these existed obvious pathological changes only in HTP_50 group, while in CS group with equivalent nicotine, hepatocytes swelling were observed in liver. CS exposure induced liver damage through mitochondrial mediated oxidative stress and inflammation, which was also observed in high concentration of HTP exposure group. For the same equivalent nicotine, HTP may show lower toxic effect on liver than CS.