Hepatotoxicity In Male Wistar Rats Research Articles

Protective effects of Butylated Hydroxytoluene (BHT) against sodium Arsenite (NaAsO2) - Induced hepatotoxicity in Wistar Rats

One of the major environmental contaminants that can be found on a global scale is arsenic. Sodium arsenite (NaAsO2) is one of the compounds of arsenic which is considered very toxic. Long term exposure to NaAsO2 can cause chemical complications in various organs of the body such as the liver, kidney, testes and brain tissues. Butylated hydroxytoluene (BHT) is an antioxidant that can serve as an antitoxic effect. NaAsO2. In this topic, we examined the chemo-protective effect of BHT on NaAsO2 induced hepatotoxicity in male Wistar rats. Wistar rats (n=42, +120g) were randomly grouped into seven treatment groups: of 7 animals each Control 1(corn oil); Control 2(distilled water); NaAsO2 alone (2.5mg/kg). BHT alone (25 mg/kg); BHT only (25mg/kg); BHT+ NaAsO2 (25mg/kg + 2.5/kg), and BHT+ NaAsO2 (2.5g/kg + 50 mg/kg) and treated for 14 days. Markers of liver functions, inflammation, oxidative stress and antioxidant profile of liver were assayed spectrophotometrically. Our results showed that exposure to NaAsO2 resulted in dramatic increase in the levels of AST, ALT and ALP activity Furthermore, NaAsO2 increased the concentration of oxidative stress markers such as xanthine oxidase (XO) and lipid peroxidation (MDA) and inflammatory markers such as myeloperoxidase (MPO) and nitric oxide (NO) with a concomitant decrease in antioxidant markers such as superoxide dismutase (SOD). Glutathione-S-transferase (GST), and catalase. However, the co-exposure of rats to both BHT and NaAsO2 can result in significant decrease the parameters above. In conclusion, exposure of rats to NaAsO2 causes increased inflammatory and oxidative stress signals, but these harmful effects can be ameliorated by administration of antioxidants such as BHT as confirmed by this research.

Protective role of resveratrol against VCM-induced hepatotoxicity in male wistar rats.

Background: Vancomycin is a glycopeptide antibiotic with a high risk of acute liver injury. Resveratrol is believed to protect the liver against toxicity. Aim: To investigate the ability of resveratrol to attenuate vancomycin-induced liver toxicity in rats injected with vancomycin. Method: Twenty-four adult male Wistar rats were distributed into three groups. The control group received only a vehicle, while the treated group received either vancomycin 200 (mg/kg, i. p.) only or vancomycin (200mg/kg, i. p.) with resveratrol (20mg/kg, oral gavage). All groups received their dose once daily for 7days. Hepatic damage was assessed by measuring biochemical parameter levels in serum, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH). Also, antioxidants and inflammation biomarkers such as Interleukin-6 (IL-6), malondialdehyde (MDA), nitric oxide (NO), and glutathione (GSH) were measured. Furthermore, the vancomycin-induced pathological changes in the liver were evaluated by histopathological studies. Results: In the vancomycin-treated group, hepatic serum biomarkers such as AST, ALT, ALP, IL-6, and MDA were elevated, while NO and GSH were depleted. However, resveratrol co-treatment with vancomycin prevented the elevation of AST, ALT, ALP, IL-6, and MDA and it protected the liver from NO and GSH depletion. Also, regarding vancomycin-induced degeneration of hepatocytes, resveratrol co-treatment with vancomycin prevented such degeneration and improved mononuclear cells in the liver. Conclusion: The results showed that oral administration of resveratrol has a significant hepatoprotective effect against vancomycin-induced hepatotoxicity.

The protective effect of naringenin against pyrazinamide-induced hepatotoxicity in male Wistar rats

BackgroundPyrazinamide (PZA) is efficient antituberculosis drug. However, PZA-induced hepatotoxicity mediated by oxidative damage is documented. Naringenin (NGN) is a common flavanone with antioxidative properties. Thus, the present work aimed to elucidate the protective role of NGN against PZA-induced toxicity in rats. Eighty adult male Wister rats were randomly divided into four groups: control, PZA, NGN and NGN+PZA. Rats were orally administered 155 mgPZA/kg or 50 mgNGN/kg or NGN 1 h before PZA daily. After 1, 2, 3 and 4 weeks, blood and liver were collected for hematological, biochemical, and histopathological investigations.ResultsAdministering PZA alone caused remarkable declines in the white and red blood cell counts, hemoglobin content, packed cell volume, and serum levels of albumin, albumin/globulin ratio, high-density lipoprotein cholesterol, and hepatic activities of superoxide dismutase, and glutathione reductase and glutathione level. Serum levels of total cholesterol, low-density lipoprotein cholesterols, triglycerides, globulin, glucose, total and indirect bilirubin, malondialdehyde, and aminotransferases activities were markedly elevated. Additionally, the liver of PZA group exhibited considerable histopathological alterations. Inversely, in the NGN+PZA group, all the aforesaid disturbances in the studied parameters were ameliorated.ConclusionsThe current study revealed that NGN can be successfully utilized during treatment with PZA to prevent its side actions.

The Ameliorative Role of Eugenol against Silver Nanoparticles-Induced Hepatotoxicity in Male Wistar Rats.

Background Silver nanoparticles (AgNPs) utilization is becoming increasingly popular. The existing investigation evaluates the ameliorative impact of eugenol (Eug) against the toxic influences of AgNPs on rats' liver. Methods Sixty adult male rats were enrolled equally into control, Eug (100 mg kg−1 orally), AgNPs-low dose (1 mg kg−1 i.p), AgNPs-high dose (2 mg kg−1 i.p), Eug + AgNPs-low dose (100 mg kg−1 orally + 1 mg kg−1 i.p), and Eug + AgNPs high dose (100 mg kg−1 orally + 2 mg kg−1 i.p). All the groups were treated daily for 30 days, subsequently serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total protein, total albumin, lactate dehydrogenase (LDH), total oxidative capacity (TOC), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), total antioxidant capacity (TAC), and interleukin 6 (IL-6) levels were measured; hepatic tissues superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and glutathione peroxidase (GPx) levels were evaluated; histopathology and histomorphometry were documented in the liver of all groups; and Bcl-2, P53, Caspase-3, and TNF-α reactive proteins were also immunohistochemically detected. Results AgNPs significantly triggered oxidative stress in hepatic tissues, characterized by elevated levels of AST, ALT, ALP, LDH, TOC, MDA, TNF-α, and IL-6 correlating with considerable decline in total protein, total albumin, TAC, SOD, CAT, GSH, and GPx. These changes were paralleled with histopathological alterations remarkable by devastation of the ordinary hepatic structure, with decrease in the numbers of normal hepatocytes, elevation in the numbers of necrotic hepatocytes, periportal and centrilobular inflammatory cells, deteriorated Kupffer cells, and dilated/congested central and portal veins. Alongside, a marked diminution in Bcl-2 immunoreactivity and a significant elevation in P53, Caspase-3, and TNF-α immunoreactivities were recorded. Supplementation of AgNPs-treated animals with Eug reversed most of the biochemical, histopathological, and immunohistochemical changes. Conclusion This study proposed that Eug has an ameliorative effect against AgNPs-induced hepatotoxicity.

Effects of Aqueous Extract of Petroselinum crispum on Liver and Hematological Parameters in Carbon Tetrachloride (CCl4) - Induced Hepatotoxicity in Male Wistar Rats

In recent years, focus on plant research has increased to show the potential of some medicinal plants in discovery of novel compounds which could be used in treatment of some diseases. Petroselinum crispum is widely used traditionally as a food additive and herbal remedy for many ailments. This study is aimed to assess the effects of Petroselinum crispum on some liver enzymes and some haematological parameters in Carbon tetrachloride (CCL4) - induced hepatotoxicity in male wistar rats. A total of 25 wistar rats were used, which were divided into 5 groups of 5 rats each. Group 1: (control); Group 2: received IP injection of 120mg/kg mixture of CCL4 and olive oil (1:1), Groups 3, 4 and 5 were orally administered 250, 500 and 1000mg/kg extract + IP injection of 120mg/kg mixture of CCL4 and olive oil for 21 days respectively. On the 22nd day, the animals were sacrifice using chloroform anesthesia and the effects of the aqueous extract were assessed by quantifying liver enzymes such as serum aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP) and total serum protein (TP). The haematological parameters were assessed by analysis of parked cell volume (PCV), red blood cell count (RBC), white blood cells (WBC), haemoglobin (Hb) concentrations and platelet count (PLT) and followed by histopathological studies of the liver tissues. The three doses of the plant extract used in this study, showed some level of protective effect on CCL4-induced hepatotoxicity as evident by the significant reduction (P < 0.05) in serum levels of AST, ALT, and ALP along with the improved histopathological liver sections compared to CCL4 -treated animals. However the extract is more effective in the 500mg/kg compared to the 250mg/kg and 1000mg/kg. Also the results obtained for all the haematological parameters used in the study showed no significant difference among all the groups (P > 0.05).

Lead exposure-induced changes in hematology and biomarkers of hepatic injury: protective role of TrévoTM supplement.

Lead exposure has been linked to health challenges involving multiple organ failure. More than fifty percent of lead present in the human body is accumulated in the liver causing hepatic injury. A major mechanism of lead toxicity is oxidative stress. Trévo™ is a nutritional supplement with numerous bioactive natural products with detoxifying and antioxidant properties. This study was designed to investigate the hepatoprotective effects of Trévo™ dietary supplements against lead-hepatotoxicity in male Wistar rats. Thirty-five healthy animals were divided into five groups of seven each as follows: Group I=control; II=15 mg/kg of lead acetate (PbA); III= 2 mL/kg of Trévo™ + PbA; IV= 5 mL/kg of Trévo™ + PbA;V=5 mL/kg of Trévo™. Animals were orally treated with Trévo™ for two days before co-administration with PbA intraperitoneally for 12 consecutive days. Animals were sacrificed 24 h after the last administration and blood were collected via cardiac puncture and processed for hematological parameters and assessment of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (ALB). The liver was excised and processed for markers of oxidative stress and histopathological examination. Intraperitoneal administration of 15 mg/kg of PbA caused a significant increase in serum concentration of AST, ALT, while the concentration of ALB was significantly decreased (P<0.001). PbA caused a significant reduction in packed cell volume, hemoglobin while the total white blood cell count, neutrophils, lymphocytes, monocytes, eosinophils, and basophils were increased. Oxidative stress was significantly pronounced in the liver of rats exposed to PbA as observed in the high concentration of malonedialdehyde, decreased concentration of glutathione, the activity of catalase, superoxide dismutase, and glutathione-S-transferase. Pretreatment with Trévo™ was able to significantly prevent the anemic, oxidative damage, and hepatic injury initiated by PbA. Histological examination also corroborated the biochemical results. In conclusion, the study reveals that Trévo™ is effective in attenuating PbA-induced hepatotoxicity in male Wistar rats.

Fabrication and evaluation of mannose decorated curcumin loaded nanostructured lipid carriers for hepatocyte targeting: In vivo hepatoprotective activity in Wistar rats

Curcumin is a well-recognized antioxidant phytoactive isolated from the rhizomes of Curcuma longa. Numerous landmark investigations have proved the antioxidant and hepatoprotective potential of curcumin. The aim of present study was to target curcumin loaded nanocarriers to hepatocytes using asialoglycoprotein receptors targeting strategy. Mannose, a water-soluble carbohydrate, was hydrophobized by anchoring stearylamine with an objective to conjugate mannose on the surface of curcumin loaded nanostructured lipid carriers for targeting asialoglycoprotein receptors on hepatocytes. Mannose conjugated stearylamine was synthesized and characterized using various analytical techniques. The synthesized targeting ligand was incorporated curcumin loaded nanostructured lipid carriers and characterized by photon correlation spectroscopy. Zeta potential measurement was used to confirm the conjugation of the synthesized ligand to the surface of drug-loaded nanostructured lipid carriers. CCl4 induced hepatotoxicity in male Wistar rats was used as an experimental animal model to evaluate the hepatoprotective potential of formulated drug encapsulated nanostructured lipid carriers. The hepatoprotective potential was assessed by measuring serum liver injury markers and oxidative stress parameters in the liver post–mitochondrial supernatant. Mannose conjugated nanostructured lipid carriers showed acceptable particle size which revealed its suitability for hepatocyte targeting. In addition to this, mannose conjugated nanocarriers revealed significantly better (p ​< ​0.05) reduction of serum liver injury markers and proinflammatory cytokines compared to the unconjugated one which confirmed hepatocytes targeting potential of the synthesized ligand. Asialoglycoprotein receptors targeting could be a landmark strategy for hepatocyte targeting. Thus, the synthesized mannose anchored stearylamine could be a promising novel targeting ligand having hepatocyte targeting potential.

Effect of silymarin on blood coagulation profile and osmotic fragility in carbon tetrachloride induced hepatotoxicity in male Wistar rats

Reports about the impact of Carbon tetrachloride (CCl4) hepatotoxicity on coagulation profile have been inconsistent. Multiple investigators have however demonstrated the effectiveness of silymarin in the resolution of anomalies induced by CCl4, although the effect of silymarin on the impact of CCl4 hepatotoxicity, especially coagulation profile and osmotic fragility have not been investigated. The liver, the primary site for the secretion of coagulation proteins, can become impaired in CCl4 hepatotoxicity, and silymarin reportedly increases hepatic protein synthesis as part of its hepatoprotective mechanism. This study assessed the effect of silymarin on blood coagulation profile and erythrocyte osmotic fragility in CCl4 induced hepatotoxicity in rats. Twenty male Wistar rats were allocated into four groups (n = 5) at random, namely: Control, CCl4 given CCl4 (1 ml/kg) administered intraperitoneally twice a week, Silymarin (S) given silymarin (100 mg/kg/day) orally, and S+CCl4 given silymarin (100 mg/kg/day) orally and (1 ml/kg) CCl4 one hour after, intraperitoneally twice a week for a duration of four weeks. Results showed protraction of activated partial thromboplastin time and thrombin time, increased erythrocyte osmotic fragility, liver damage, dyslipidemia, oxidative stress and lipid peroxidation in rats given CCl4. Silymarin attenuated most of these effects as observed from comparison between CCl4 and S+CCl4 rats. The findings of this study suggests that pretreatment with silymarin attenuated disruption in coagulation profile and erythrocyte osmotic fragility in CCl4 induced hepatotoxicity in Wistar rats.

Potential Effects of Boldine on Oxidative Stress, Apoptosis, and Inflammatory Changes Induced by the Methylprednisolone Hepatotoxicity in Male Wistar Rats.

BackgroundSynthetic glucocorticoid therapeutic agent methylprednisolone (MPL), when used for an extended period of time at high dose, promotes the development of reactive oxygen species (ROS)-induced liver toxicity. This study investigated the role of boldine, a natural antioxidant with anti-apoptotic and anti-inflammatory properties, against MPL-induced hepatoxicity in male Wistar rats.Methods120 rats were divided into eight equal groups: G1 (control), G2, 3, and 4 (rats orally administered 5, 10, and 50 mg boldine/kg b.w./day; respectively, for 28 days), G5 (rats intramuscularly injected with 100 mg MPL/kg b.w. only on the last three days), G6, 7, and 8 (rats administered boldine + MPL). After the last MPL injection, rats were sacrificed at intervals of 1, 24, and 48 h.ResultsThere was a significant decrease in WBCs, RBCs count, and HGB levels, as well as an increase in PLT count, ALT, AST, TG, and LDL levels, and a decrease in HDL level in serum. Oxidative stress markers levels increased at all times, and gene expression of antioxidant enzymes increased at 24h. Immunohistochemical analysis revealed that cytochrome c levels significantly increased after MPL treatment. The COMET assay revealed detectable DNA lesions. There was no immune reactivity of IL-6 expressions as an inflammatory response marker.ConclusionsOral administration of boldine has a modulatory protective, antioxidant, and anti-apoptotic effect against free radicals.

Diosmin Alleviates Doxorubicin-Induced Liver Injury via Modulation of Oxidative Stress-Mediated Hepatic Inflammation and Apoptosis via NfkB and MAPK Pathway: A Preclinical Study.

Hepatotoxicity caused by chemotherapeutic drugs (e.g., doxorubicin) is of critical concern in cancer therapy. This study focused on investigating the modulatory effects of diosmin against doxorubicin-induced hepatotoxicity in Male Wistar rats. Male Wistar rats were randomly divided into four groups: Group I was served as control, Group II was treated with doxorubicin (20 mg/kg, intraperitoneal, i.p.), Group III was treated with a combination of doxorubicin and low-dose diosmin (100 mg/kg orally), and Group IV was treated with a combination of doxorubicin and high-dose diosmin (200 mg/kg orally) supplementation. A single dose of doxorubicin (i.p.) caused hepatic impairment, as shown by increases in the concentrations of serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Doxorubicin produced histological abnormalities in the liver. In addition, a single injection of doxorubicin increased lipid peroxidation and reduced glutathione, catalase, and superoxide dismutase (SOD) levels. Importantly, pre-treatment with diosmin restored hepatic antioxidant factors and serum enzymatic activities and reduced the inflammatory and apoptotic-mediated proteins and genes. These findings demonstrate that diosmin has a protective effect against doxorubicin-induced hepatotoxicity.

Effects of Aloysia citriodora Hydroalcoholic Extract on Ethanol-induced Hepatotoxicity in Male Wistar Rats

Background: Chronic ethanol consumption presents toxic effects on liver tissue by inducing oxidative stress and inflammation. The antioxidant and anti-inflammatory properties of lemon verbena were established. Objectives: The present study aimed to evaluate the protective effects of the hydroalcoholic extract of Aloysia citriodora (A. citriodora) on ethanol-induced hepatotoxicity in male rats by evaluating inflammatory and oxidative stress factors. Methods: The study animals were randomly divided into 7 groups, (6/group) including control, extract alone (400mg/kg), ethanol 10 mg/kg, vitamin C 500 mg/kg + ethanol 10 mg/kg, and the fifth, sixth and seventh groups respectively received an intraperitoneal injection of 100, 200, and 400 mg/kg of A. citriodora extract plus ethanol once a day for 6 weeks. Oxidative stress parameters, such as glutathione content, lipid peroxidation, protein carbonyl, and reactive oxygen species were measured. Furthermore, inflammation parameters (nitric oxide) and liver damage were evaluated by determining the levels of liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and histopathological examinations. Results: In the liver tissue of the ethanol-receiving group, a significant increase (P&lt;0.001) was observed in ALT, AST, and ALP levels and pathological changes, compared to the control group. There was also a significant increase in the levels of oxidative stress and inflammatory factors. Interestingly, A. citriodora extract could inhibit ethanol-induced liver damage by suppressing oxidative stress and inflammation. Conclusion: A. citriodora extract significantly attenuated inflammation and oxidative stress caused by ethanol. Therefore, it can be suggested as a beneficial supplement for treating ethanol-induced hepatotoxicity.

The protective potential of alpha lipoic acid on amiodarone-induced pulmonary fibrosis and hepatic injury in rats.

Amiodarone (AMD) is a widely used antiarrhythmic drug prescribed to treat cardiac tachyarrhythmias; however, AMD has been reported to provoke pulmonary fibrosis (PF) and hepatotoxicity. This study aimed to investigate the influence of alpha lipoic acid (ALA) on AMD-induced PF and hepatotoxicity in male Wistar rats. AMD administration resulted in elevated lung contents of hydroxyproline (Hyp), malondialdehyde (MDA), and increased serum levels of transforming growth factor beta-1 (TGF-β1), interferon-γ (IFN-γ), alanine amino transaminase (ALT), aspartate amino transaminase (AST), total cholesterol (TC), and glucose. On the other side, lung content of glutathione reduced (GSH) and serum levels of total anti-oxidant capacity (TAC) were significantly decreased. Histopathologically, AMD caused PF, produced a mild hepatic injury, and increased expression of alpha smooth muscle actin (α-SMA). Treatment with ALA produced a significant reversal of the oxidative stress, fibrosis, and inflammation parameters with reductions in α-SMA expressions, leading to amelioration of histopathological lesions. ALA might provide supportive therapy in AMD-receiving cardiovascular patients.

Bioactive Compounds from Mango peels (Mangifera indica .Tommy Atkins) And Demonstration of its Cytotoxicity and CCl4 Induced Hepatotoxicity in Rat

Mangifera indica (Tommy Atkins) peels, commonly known as mango, is a pharmacologically, ethnomedically, and phytochemically diverse plant. Peels is a major by-product during processing of mango fruit into pulp. In the present study, Thirteen pure bioactive compounds were isolated from methanolic peels extract. Six of them are new ellagitannins,namely,1,2,3,4,6 -Penta-O-galloyl-s-4C1-glupyranose (3); 2,3,6-Tri-O-galloyl-(α/β)-4C1-glucopyranose(4); 2,3-Di-O-galloyl-(α/β)-4C1-glucopyranose,Nilocitin(6);3,6-Di-O-galloyl-(α/β)-4C1-glucopyranose(8);1,6 -Di-O-galloyl- β-4C1-glucopyranose (9) ; 1,3-Di-O-galloyl-β-4C1- glucose (11), which were analyzed for the first time from M. indica (Tommy Atkins) peels. The ameliorative effect of the methanolic extract of M. indica (Tommy Atkins) peels towards the CCl4-induced hepatotoxicity in male Wistar rats through measuring certain biochemical parameters content in the liver were analyzed. The CCl4-treated rats showed a significant decline in the studied the serum levels of high-density lipoprotein (HDL), albumin (A) as well as the hepatic levels of glutathione (GSH) and activities of catalase (CAT), superoxide dismutase (SOD) , glutathione reductase (GR), elevation in the levels of total lipids (TL), triglycerides (TG), total cholesterol (TC), low-density lipoproteins (LDL), globulin (G), total bilirubin (TBil) , alanine and aspartate aminotransferase and alkaline phosphatase (ALAT and ASAT, ALP) and the hepatic levels of malondialdehyde (MDA). In contrast, the administration of methanol extract, notably improved all the studied parameters. This study showed that CCl4 administration to Wistar rats, at a high dose level, could induce a hepatic injury in addition to certain metabolic alterations. The work was extended to investigate tissue histopathology. Thus, results suggest that the peels extract can be a potential source of an attractive candidate for ameliorating of hepatotoxicity induced by CCl4 through scavenging free radicals, improved liver functions, and normalizing the liver histopathological architecture.

GC/MS-Based Metabolomics Profiling Approach and Determination of Ameliorative effect of Chiliadenus montanus extract towards CCl4 induced Hepatotoxicity in Albino Rats

The current study aimed to evaluate the GC/MS profiling of Chiliadenus montanus leaves extract which consists of 48 compounds, nine of them are major and represented 52.55 % from the total peak areas. The ameliorative effect towards the CCl4-induced hepatotoxicity in male Wistar rats through measuring certain biochemical parameters content in the liver were analyzed. CCl4 diluted 1:9 (v/v) in olive oil was injected intraperitoneally followed by oral administration of methanolic plant extract (200 mg/kg body weight). The CCl4-treated rats showed a significant decline in the studied hematological parameters, the serum levels of high-density lipoprotein (HDL), albumin (A) as well as the hepatic levels of glutathione (GSH) and activities of catalase (CAT), superoxide dismutase (SOD) , glutathione reductase (GR), elevation in the levels of total lipids (TL), triglycerides (TG), total cholesterol (TC), low-density lipoproteins (LDL), globulin (G), total bilirubin (TBil) , alanine and aspartate aminotransferase and alkaline phosphatase (ALAT and ASAT, ALP) and the hepatic levels of malondialdehyde (MDA). In contrast, the administration of methanol extract, notably improved all the studied parameters. This study showed that CCl4 administration to Wistar rats, at a high dose level, could induce a hepatic injury in addition to certain hematologic and metabolic alterations. The work was extended to examine tissue histopathology. In conclusion, C. montanus leaves methanol extract, resulted in an attractive candidate for ameliorating of hepatotoxicity induced by CCl4 through scavenging free radicals, improved liver functions, and normalizing the liver histopathological architecture. Yet, the treatment with methanol extract could ameliorate these alterations via their antioxidative effect. Further studies are required in order to identify the molecules responsible of the pharmacological activities.

Ameliorating and anti-inflammatory role of Balanites aegyptiaca aqueous extract on Doxorubicin-induced hepatotoxicity in male Wistar rats

Background and objective Doxorubicin (Doxo) is an antibiotic that used in cancer treatment, with many complications like hepatotoxicity. The objective of this study was to explore the ameliorative effect of Balanites aegyptiaca aqueous extract (BAE) against Doxo-induced hepatotoxicity in male rats. Materials and methods Adult male Wistar rats (140–160 g) were randomly divided into six groups (10 animals each) as follows: group I, normal rats act as a control group; group II, rats ingested with BAE (200 mg/kg) for 4 weeks; group III, rats intoxicated (intraperitoneal) with Doxo (0.5 mg/kg) for 4 weeks; group IV, rats ingested with BAE in combination with Doxo injection for 4 weeks; group V, rats ingested with BAE for 4 weeks before Doxo injection for another 4 weeks; and group VI, rats ingested with BAE for 4 weeks after Doxo injection. Results The results revealed all BAE regimens succeeded to decrease the hepatotoxicity induced by Doxo. This was evidenced by the significant reduction of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, urea, creatinine, tumor necrosis factor alpha, and interleukin-1beta levels, as well as hepatic malondialdehyde and nitric oxide levels. Moreover, a marked increase was observed in serum protein and albumin levels, as well as hepatic-reduced glutathione, superoxide dismutase, and catalase values. The obvious histopathological regenerations came in line with both serum and tissue biochemical findings. The Doxo-BAE combined regimen exhibited the highest potential of amelioration. Conclusion As a promising supplement, BAE exhibited hepatoprotective potential against Doxo-induced hepatic injuries; this could be mechanized through its antioxidant and radical scavenging exhibition of its bioactive constituents.

Naringin and Hesperidin Counteract Diclofenac-Induced Hepatotoxicity in Male Wistar Rats via Their Antioxidant, Anti-Inflammatory, and Antiapoptotic Activities.

This study is aimed at evaluating the preventive effect and at suggesting the mode of actions of naringin and hesperidin and their combination in diclofenac-induced hepatotoxicity. Male Wistar rats, intraperitoneally injected with diclofenac sodium (3 mg/kg b.wt/day), were orally treated with naringin (20 mg/kg b.wt/day) and hesperidin (20 mg/kg b.wt/day) and their combination for 4 weeks. The administrations of naringin and hesperidin to diclofenac-injected rats led to a significant decrease in the elevated serum ALT, AST, LDH, ALP, GGT, total bilirubin, TNF-α, and IL-17 levels as well as liver lipid peroxidation and liver p53 and caspase-3 mRNA expressions. In contrast, serum IL-4 level, liver GSH content, and liver GPx and SOD activities increased. In association, diclofenac-induced deleterious histological alterations including hydropic degeneration, cytoplasmic vacuolization, apoptosis, and focal hepatic necrosis of hepatocytes associated with inflammatory cells' infiltration were remarkably improved by treatments with naringin and hesperidin. In conclusion, naringin, hesperidin, and their combination, which was the most potent, counteract diclofenac-induced liver injury via antioxidant, anti-inflammatory, and antiapoptotic actions. Thus, this study recommends the use of naringin and hesperidin or their combination to resolve the side effects of drugs like diclofenac on the liver.

Attenuation of Carbon Tetrachloride – Induced Hepatoxicity by Dacryodes edulis Seeds Ethanolic Extract in Male Wistar Rats

Dacryodes edulis (African pear) seed has a long history of use in ethnomedicine. However, there is a paucity of information on its ameliorative potential on hepatic damage. In the present study, the potentials of D. edulis ethanolic seed extract (DET) in attenuating carbon tetrachloride (CCl4)-induced hepatotoxicity in male Wistar rats was assessed. Ninety male Wistar rats were divided into 3 groups (n = 10) designated: control, CCl4, and DET, respectively. Animals in the control group were administered 2 mL/kg body weight corn oil, while those assigned to CCl4 and DET groups were administered i.p. 30% CCl4 in corn oil (1:1 v/v) at 2 mL/kg. Treatment was administered once every 24 h consecutively for 72 h. Thereafter, control and CCl4 groups were treated once daily with 1 mL distilled water by gavage, while DET rats were treated once daily with 1500 mg/kg DET by gavage. At every 7 days interval and for 28 consecutive days, animals were starved overnight, weighed, and six rats from each group were sacrificed under anesthesia to collect blood and liver samples. After 28 days, remarkable improvements in feed intake, body weight, serum levels of hepatic function indicators, and hepatic histology were observed in DET rats compared to CCl4 rats. These results suggest a possible ameliorative potential of D. edulis ethanolic seed extract against CCl4-induced hepatic injury.

Effects of Carica papaya Seeds on Acetaminophen-Induced Hepatotoxicity in Male Wistar Rats

Effects of Carica papaya Seeds on Acetaminophen-Induced Hepatotoxicity in Male Wistar Rats

RETRACTED ARTICLE: Determination of histopathological and biomedical parameters in protective effects of Petroselinum crispum on hepatotoxicity induced by dichlorvos in male Wistar rats

Dichlorvos (Dich), an organophosphate substance, is widely used as an insecticide with various side effects on humans. Petroselinum crispum with antioxidant properties (PC) has many therapeutic benefits. This study examines the detoxification feature of PC on Dich-induced hepatotoxicity in male Wistar rats. Sixty-four male Wistar rats were grouped into eight including sham (normal saline), Dich (4 mg/kg/day), PC 1, 2, 3 (100, 150, 200 mg/kg/day, respectively) and Dich+PC 1, 2, 3 (100, 150, 200 mg/kg/day, respectively). All treatments were applied intraperitoneally (i.p) at 10 A.M. daily for 4 weeks. A day after the last treatment, the animals were sacrificed by cervical dislocation. The histopathological changes and apoptosis processes were assessed by light and fluorescent microscopy methods. The serum levels of hepatic enzymes, nitrite oxide (NO), and total antioxidant capacity (TAC) were evaluated. Dich significantly increased NO level, hepatic enzymes activity, apoptosis, mean diameter of hepatocytes (DH), and central hepatic vein diameter (CHVD) and also decreased TAC, mean weight of liver, and a total weight of rats compared to the sham group (P < 0.01). In all doses of PC and Dich+PC groups, a significant decrease was detected in values of apoptosis, hepatic enzymes activity, NO level, mean DH, and CHVD while an increase in TAC level, means of liver weight, and a total weight of rats was observed compared to the Dich group (P < 0.01). PC by antioxidant property can recover the catastrophic liver changes induced by Dich administration.

Antioxidant and Hepatoprotective Effect of Cajanus cajan in N-Nitrosodiethylamine-Induced Liver Damage

N-Nitrosodiethylamine (NDEA) is a nitrosamine derivative with carcinogenic and mutagenic properties which can be found in tobacco smoke, meat and various food products. This study examined the antioxidant and hepatoprotective potential of Cajanus cajan (C. cajan) with respect to hepatotoxicity in male Wistar rats. Administration of NDEA induced hepatotoxicity at 200 mg/kg while C. cajan was administered (200, 400 and 800 mg/kg) for 28 days. NDEA-induced hepatotoxicity significantly (p ≤ 0.05) increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and malondialdehyde (MDA) and significantly (p ≤ 0.05) decreased reduced glutathione (GSH), albumin (ALB), glutathione S-transferase (GST), catalase (CAT) and superoxide dismutase (SOD). C. cajan-treated groups were seen to have significantly (p ≤ 0.05) decreased ALT and AST and significantly (p &lt; 0.05) increased ALB, GST, GSH, SOD and CAT. The NDEA-treated group also showed a marginal increase in body weight and a significant (p ≤ 0.05) increase in liver weight. The C. cajan treated groups showed a significant (p ≤ 0.05) increase and decrease respectively in body and liver weights. Histopathological changes also substantiated NDEA-induced hepatotoxicity and the hepatoprotective effect of C. cajan on the liver. The results indicate that C. cajan has the potential to ameliorate NDEA-induced hepatotoxicity.