Hepatic Damage In Rats Research Articles

The Interaction of Apical Periodontitis, Cigarette Smoke, and Alcohol Consumption on Liver Antioxidant Status in Rats

This study aimed to investigate the impact of alcohol (A), secondhand cigarette smoking (ShS), and their combined effect on liver antioxidant activity and hepatic damage in rats with induced apical periodontitis (AP). Thirty-five female Wistar rats were randomly allocated into five groups (n = 7): (1) control (rats without ShS, alcoholic diet, or AP), (2) control-AP (induced AP only), (3) ShS-AP (ShS exposure and induced AP), (4) A-AP (alcoholic diet and induced AP), and (5) A+ShS-AP (alcoholic diet, ShS exposure, and induced AP). Alcohol was administered through semi-voluntary intake, while ShS exposure involved the daily inhalation of cigarette smoke. The experimental period lasted 8 weeks, with AP induction occurring in the 4th week following molar pulp exposure. Liver samples were collected post-euthanasia for histomorphometric and antioxidant marker analyses. All AP-induced groups exhibited increased liver sinusoidal dilation compared to the control group (p < 0.05). AP significantly reduced total antioxidant capacity (FRAP) across all groups (p < 0.05). In AP-induced groups, FRAP levels were further decreased in ShS-AP and A+ShS-AP compared to control-AP (p < 0.05). AP also led to a decrease in the glutathione defense system (p < 0.05). Rats with alcohol exposure (A-AP and A+ShS-AP) showed reduced glutathione peroxidase activity (p < 0.05). Glutathione reductase activity was comparable in the control and control-AP groups (p > 0.05), but significantly decreased in the alcohol and ShS-exposed groups (p < 0.05). Apical periodontitis can relate to morphological changes in the liver’s sinusoidal spaces and impairment of liver’s antioxidant capacity of rats, particularly when combined with chronic alcohol consumption and exposure to cigarette smoke.

Saroglitazar ameliorates 5- Fluorouracil-induced hepatorenal damage in rats

RationaleHepatotoxicity and nephrotoxicity are significant adverse effects caused in cancer patients treated with 5-Flurouracil (5-FU), a pyrimidine analogue anti-metabolite anticancer drug. The purpose of this research was to evaluate the impact of PPAR α/γ agonist (Saroglitazar; SARO) on 5-FU-induced hepatorenal damage in rats. MethodsMale rats were randomly assigned to four groups: control, 5-FU, 5-FU + SARO (2 mg/kg), and 5-FU + SARO (4 mg/kg). Rats received 75 mg/kg 5-FU intraperitoneally once weekly for three weeks. Saroglitazar (2 and 4 mg/kg/day) was orally supplied by oral syringe for three consecutive weeks. On day 22, rats were euthanized and their livers and kidneys were subjected to morphological, biochemical, histological, and immunohistochemical analysis. ResultsSaroglitazar treatment significantly decreased serum liver and kidney function biomarkers. In addition, it successfully modulated liver and kidney levels of inflammatory mediators and markers (NF-κB P65, TNF-α, cleaved caspase-1, IL-1β and p-p38 MAPK) and oxidative stress-related parameters (MDA, GSH, SOD, Keap1, Nrf-2 and HO-1) in a dose dependent manner. Furthermore, SARO could attenuate 5-FU-induced activation of cleaved caspase-3 as well as improved histopathological examination of both liver and kidney tissues. Significance: Saroglitazar may be a viable therapy option for 5-FU toxicity as it halts the interaction network of NF-kB and Nrf2 signaling pathways and apoptosis.

Thymoquinone attenuates diabetes-induced hepatic damage in rat via regulation of oxidative/nitrosative stress, apoptosis, and inflammatory cascade with molecular docking approach

Diabetes mellitus (DM) is a complex metabolic condition that causes organ dysfunction. The current experiment sought to determine the effect of thymoquinone (TQ) on hyperglycemia, hyperlipidemia, oxidative/nitrosative stress, inflammation, and apoptosis in diabetic rats prompted by streptozotocin (STZ) (55 mg/kg body weight i/p). The animals were allocated into control, TQ (50 mg/kg B.W. orally administered for 4 succeeding weeks), Diabetic, and Diabetic + TQ groups. This study confirmed that TQ preserves the levels of insulin, fasting blood glucose, HOMA β-cell indices, HbA1c %, body weight, and lipid profile substantially relative to the DC group. Furthermore, hepatic antioxidant (CAT, GSH, and T-SOD) values were reduced. Conversely, the enzymatic activity of liver functions (AST, ALT, ALP, cytochrome P450, and hepatic glucose-6-phosphatase), lipid peroxidation (MDA), pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6), nitric oxide (NO) and inflammatory marker (CRP) enhanced with STZ administration, which is substantially restored after TQ treatment. Relative to the diabetic rats, TQ reestablished the hepatic architectural changes and collagen fibers. Additionally, TQ downregulated the intensity of the immunohistochemical staining of pro-apoptotic marker (caspase-3), p53, and tumor necrosis factor-alpha (TNF-α) proteins in hepatic tissues. Furthermore, TQ displayed abilities to interact and inhibit the binding site of caspase-3, interleukin-6 receptor, interleukin-1 receptor type 1, TNF receptor superfamily member 1A, and TNF receptor superfamily member 1B in rats following the molecular docking modeling. All these data re-establish the liver functions, antioxidant enzymes, anti-inflammatory markers, and anti-apoptotic proteins impacts of TQ in STZ-induced DM rats. Founded on these outcomes, the experiment proposes that TQ is a novel natural supplement with various clinical applications, including managing DM, which in turn is recommended to play a pivotal role in preventing the progression of diabetes mellitus.

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.

Quercetin and hesperidin protection against hepato-renal damage occasioned by carbon tetrachloride (CCL4) in a rat model

BackgroundCurrent pharmacological research has shown that medicinal plants have notable bioactivities. For more than a millennium, traditional Chinese medicine (TCM) has prescribed CRP primarily as a qi-regulating medication for therapeutic purposes. Hence, the synergistic effect of the two medicinal plants on the hepato-renal damage in rats exposed to CCL4. Materials and MethodsFor twenty-one days, rats were gavaged with quercetin and hesperidin (2.4 and 2.4 mg/kg each) after being exposed to CCL4 (0.5 mg/kg). Samples were taken to evaluate several biochemical markers. Nitric oxide (NO), hydrogen peroxide (H2O2), and malondialdehyde (MDA) were measured. The activity of the enzymes alanine transferase (ALT) and alkaline phosphatase (ALP) were estimated to represent liver function. Catalase (CAT), Glutathione peroxidase (GPx), and Glutathione (GSH) levels were evaluated for antioxidant level, total bilirubin, total protein, urea, uric acid, and creatinine), as well as histopathology were assessed. ResultsThe concentration of total bilirubin, total protein, urea, uric acid, creatinine, increased considerably (P < 0.05) after exposure to carbon tetrachloride, with the levels of H2O2, MDA, SOD, CAT, GPX, GSH, and the activities of ALT and AST in serum, also, changes observed in histopathological findings. Upon treatment with the extracts, the levels of H2O2 and MDA was significantly (P < 0.05) reduced and modify SOD, CAT, GPX, GSH, ALT, and ALP activities in rats substantially (P < 0.05). With slid changes on histopathological effect. ConclusionQuercetin and hesperidin treatment successfully improved liver and kidney pathophysiology and reduce the level of ROS. Thus, quercetin and hesperidin can be recommended as a hepato-renal preventive agent against CCL4-induced toxicity.

Hepatoprotective effect of the ethanol extract of Detarium senegalense stem bark in albino Wistar

Aim: The hepatoprotective effect of Detarium senegalense ethanol stem bark extract was evaluated against paracetamol induced hepatic damage in albino rats. Material and methods: The ethanol stem bark extract of D. senegalense at doses of 100 mg/kg, 200 mg/kg and 400 mg/kg were orally administered once daily for 3 days.The liver function tests and biochemical investigation such as asparte transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (TB) and direct bilirubin were carried out against paracetamol induced hepatotoxicity in rats. Phytochemical investigation was performed to find active constituents of the plant extracts by the different phytochemical tests. Results: Pre-treatment with the ethanol stem bark extract significantly prevented the biochemical, histological, and changes induced by paracetamol in the liver. The extract showed significant hepatoprotective effects as evidenced by decreased serum enzyme activities such as AST, ALT,, ALP, TB and DB which was supported by histopatological assessment of the liver.The ethanol stem bark extract exhibited significant hepatoprotective activity comparable with silymarin, the standard drug as well as hepatotoxin agent, paracetamol. The phytochemical screening of the extract revealed the presence of alkaloids, saponins, tannins, flavonoids, terpenoids, steroids, cardiac glycosides, resins and balsam. Conclusion: The results of this study strongly show that ethanol stem bark extract of Detarium senegalense possess a potent hepatotoxicity activity against paracetamol induced hepatic damage in rats.

Liver-boosting potential: chicory compound-mediated silver nanoparticles for hepatoprotection-biochemical and histopathological insights.

Background: Liver disease is a serious health concern in today's world, posing a challenge to both healthcare providers and pharmaceutical companies. Most synthetic drugs and chemicals cause liver damage accounting for approximately 10% of acute hepatitis and 50% of acute liver failure. Purpose: The present study aimed to evaluate the hepato-protective activity of an extract of chicory formulation assisted by silver nanoparticles against carbon tetra chloride (CCl4)-induced hepatic damage in rat's liver. Methods: Rats of the Wistar strain (Rattus norvegicus) were used to test the in vivo hepato-protective efficacy at various doses. Rats were randomly divided into nine groups, each containing six rats. The groups were as follows: first group (control), second group (CCl4), third group, silymarin (20mg/kg of body weight), fourth group (CCl4+chicory) (1.75mg/kg of b. wt), fifth group (CCl4 + chicory at the dose of 2.35mg/kg), sixth group (CCl4 + chicory of 3.25mg/kg), seventh group (CCl4 +AgNPs 1.75mg/kg of b. wt.), eighth group (CCl4 + AgNPs 2.35mg/kg of body weight), and ninth group (CCl4 + AgNPs 3.25mg/kg of b. wt.). Blood samples were taken 24h after the last administration (i.e., 30th day). The blood samples were analyzed for different serum enzymes such as ALP (alkaline phosphatase), ALT (alanine transaminase), bilirubin (Blr), triglyceride, and cholesterol. Histology liver sections were performed. Results: Treatment with AgNPs and chicory extract showed significant hepato-protective activity in a dose-dependent manner. In three doses, the chicory extract at a rate of 3.25mg/kg of body weight significantly reduced elevated levels of biochemical markers in comparison to CCl4-intoxicated rats. Histology of the liver sections from CCl4-treated rats revealed inflammation of hepatocytes, necrosis, cytoplasmic degeneration, vacuolization, and a deformed central vein. The chicory formulation extract exhibited a remarkable recovery percentage in the liver architecture that was higher than the drug (i.e., silymarin). While treatment with AgNPs also repaired the degenerative changes and restored the normal form of the liver, chicory formulation extract possessed more hepato-protective potential as compared to AgNPs by regulating biochemical and histo-pathological parameters. Conclusion: This study can be used as confirmation of the hepato-protective potential of chicory compounds for possible use in the development programs of drugs to treat liver diseases.

Therapeutic benefit of melatonin in 5-fluorouracil-induced renal and hepatic injury.

Nephrotoxicity and hepatotoxicity include increased oxidative stress and apoptosis; as a result, liver and kidney damage are related to its pathogenesis. These are significant side effects caused in cancer patients treated with 5-FU. In the research, 25 rats were divided into five groups, including control, 5-FU and 5-FU + 2.5, 5 and 10 mg/kg melatonin (MEL), and the protective impact of MEL against 5-FU-induced hepatorenal damage in rats was investigated. 5-FU caused significant harm, resulting in severe renal failure and histopathological changes. It also increased BUN, creatinine and hepatic function markers levels while decreasing superoxide dismutase and glutathione peroxidase activity. Additionally, 5-FU led to a notable increase in malondialdehyde content. However, MEL co-administration to rats reversed most biochemical and histologic effects. In the control and MEL + 5-FU groups, the values were comparable. The doses of MEL treatment had a significant positive impact on 5-FU-induced oxidative stress, apoptosis, lipid peroxidation and kidney damage. Our data concluded that MEL has an ameliorative effect on hepatorenal damage caused by 5-FU.

Didymin protects against polystyrene nanoplastic-induced hepatic damage in male albino rats by modulation of Nrf-2/Keap-1 pathway.

Polystyrene nanoplastics (PS-NPs) are ubiquitous environmental pollutants that can cause oxidative stress in various organs, including the liver. Didymin is a dietary flavanone that displays multiple pharmacological activities. Therefore, the present study evaluated the palliative role of didymin against PS-NPs-induced hepatic damage in rats. Albino rats (n=48) were randomly distributed into 4 groups: control, PS-NPs treated group, PS-NPs + didymin co-administered group, and didymin supplemented group. After 30 days, PS-NPs intoxication lowered the expression of Nrf-2 and anti-oxidant genes [catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GSR), glutathione-S-transferase (GST), and heme oxygenase-1 (HO-1)], whereas the expression of KEAP1 kelch like ECH associated protein 1 (Keap-1) was increased. PS-NPs exposure also reduced the activities of anti-oxidants enzymes (CAT, SOD, GPx, GSR, GST, GSH, and OH-1), while malondialdehyde (MDA) and reactive oxygen species (ROS) levels were increased. The levels of alanine transaminase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were increased in PS-NPs-exposed rats. Moreover, inflammatory indices [interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), nuclear factor-kappa B (NF-κB), and cyclooxygenase-2 (COX-2)] were increased in PS-NPs-exposed rats. Furthermore, PS-NPs intoxication increased the expressions of apoptotic markers including Bax and Caspase-3, as well as reducing Bcl-2 expression. The histopathological analysis showed significant damage in PS-NPs-treated rats. However, didymin supplementation ameliorated all the PS-NPs-induced damage in the liver of rats. Therefore, it was concluded that didymin can act as a remedy against PS-NPs-induced liver toxicity due to its anti-apoptotic, anti-oxidant, and anti-inflammatory activities.

Ameliorative and protective effect of Bergenia ciliata (Haw.) Sternb. extract against acetaminophen-induced hepato-renal damage in rats: B. ciliata and hepato-renal damage

Background: Bergenia ciliata (Haw.) Sternb. is a medicinal plant bestowed with antioxidative phytochemicals and has been traditionally associated with several medicinal and health-promoting properties and used in the management of diseases.Method: The study was undertaken to determine the potential of the extract of the rhizome of Bergenia ciliata (Haw.) Sternb. at 150 and 300 mg/kg body weight (BW) to attenuate the drug-induced oxidative damage in hepatic and renal tissues of Wistar rats. The toxicity was induced by a single oral administration of acetaminophen (APAP).Results: The oral administration of APAP significantly altered the levels of hepatic and renal damage indicators in Wistar rats. The levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-s-transferase (GST) and total thiols (TTH) decreased significantly in erythrocytes, hepatic and renal tissues. Administration of B. ciliata (150 mg/kg BW) significantly decreased the elevated hepato-renal biomarkers and malondialdehyde (MDA) levels in the tissues whereas significantly increased the levels of SOD, GST and TTH in erythrocytes and liver. The higher dose of B. ciliata (300 mg/kg BW) restored the levels of plasma hepatic and renal biomarkers as well as antioxidant parameters (SOD, GST, GPx, TTH and MDA). It also reversed the histopathological alterations in hepato-renal tissues indicating the protective potential of the extract.Conclusions: Overall, the results indicated that the B. ciliata rhizome extract attenuated the drug-induced hepato-renal toxicity in a dose-dependent manner in Wistar rats and therefore, has the potential for future therapeutic uses.

Protective effect of Ageratum conyzoides against carbon tetrachloride –induced hepatic damage in rats

The present study was conducted toexamine the Hepatoprotective activity against the carbon tetrachloride toxicity in Wister rats. The Petroleum ether, ethyl acetate and methanol extract of was prepared and evaluated for phytochemical screening. The serum level of glutamic oxaloacetate transaminase (SGOT) Glutomicpyruvate transaminase (SGPT) and bilirubin were investigated for the assessment of hepatoprotective activity of ethyl acetate of extract . Additionally, the histological changes in liver were studied. The primary phytochemical investigation of the extract of revealed the presence of Flavonoids, tannins, and carbohydrates. Pretreatment with ethyl acetate extract of showed a significant (P&amp;#60;0.05) decrease in serum SGOT, SGPT and bilirubin when compared to control group rats treated with CCl in dose dependent manner. The outcomes of histology study revealed that there was significant reversal of histological functions of liver. In conclusion, the findings of study validated that the can improve CCl–induced hepatic toxicity.

Phenolic Content, Antioxidant and Hepatoprotective Activities of Sabah Hoya coronaria Blume

A common challenge that regularly results from oxidative stress is hepatic damage. This condition is characterised by a gradual progression from steatosis to chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The study proposed to assess the antioxidant activity and efficacy of Hoya coronaria aqueous extract in preventing CCl4-induced hepatic damage in rats. The DPPH technique was used in the study to assess the extract's antioxidant properties. The rats received dosages of 125 and 250 mg/kg body weight of H. coronaria extract for 14 days, followed by CCl4 exposure. After two weeks, the rats were euthanised for analysis. The results indicated that the extract showed significant antioxidant potential and decreased the impact of CCl4 on hepatic damage markers such as serum aspartate transaminase and alanine transaminase. Moreover, it increased hepatic reduced glutathione and various antioxidant enzymes while reducing malondialdehyde formation induced by CCl4. Additionally, the histopathological analysis demonstrated that H. coronaria extract protected the liver against fatty degeneration and necrosis induced by CCl4 toxicity. These outcomes suggest that H. coronaria extract could be used to prevent ROS-related hepatic damage.

Curative effects of kaempferide on cadmium-instigated hepatotoxicity in male albino rats

Cadmium (Cd) is an environmental and industrial toxicant that possess the ability to cause severe health issues to humans and animals. The flavonol, kaempferide (KF), exhibits multiple pharmacological potentials. Therefore, this investigation was designed to estimate the mitigative effect of KF against Cd instigated hepatic damage in rats. 24 albino rats (male) were kept in 4 different groups. The group-1 was designed as untreated/control group, group-2 was orally provided with Cd (5 mg/kg), group-3 was orally co-administrated with Cd (5 mg/kg) along with KF (20 mg/kg) and group-4 was supplemented with KF (20 mg/kg) during 30 days of trial. Cd administration significantly escalated ALT, ALP as well as AST levels. A substantial decline in SOD, GST, POD, CAT, GSR activities and GSH content was observed due to Cd exposure along with an elevation in TBARS and H2O2 levels. Moreover, Cd administration elevated NF-kB, IL-6, TNF-α as well as IL-1β levels in addition to the activity of COX-2. Furthermore, the levels of Bax, Caspase-9 as well as Caspase-3 were escalated, besides the level of Bcl-2 was decreased after Cd exposure. A significant increase in histopathological damages after Cd administration is a clear indication of liver damage. However, co-treatment of KF with Cd potential recovered all the damages and significantly reduced the biochemical and histological variations in rat liver. Overall results indicated that KF has efficient anti-oxidant properties, which mitigated Cd instigated hepatic damage in rats.

The Potential Effects of Quercetin-Loaded Nanoliposomes on Amoxicillin/Clavulanate-Induced Hepatic Damage: Targeting the SIRT1/Nrf2/NF-κB Signaling Pathway and Microbiota Modulation.

Amoxicillin/clavulanate (Co-Amox), a commonly used antibiotic for the treatment of bacterial infections, has been associated with drug-induced liver damage. Quercetin (QR), a naturally occurring flavonoid with pleiotropic biological activities, has poor water solubility and low bioavailability. The objective of this work was to produce a more bioavailable formulation of QR (liposomes) and to determine the effect of its intraperitoneal pretreatment on the amelioration of Co-Amox-induced liver damage in male rats. Four groups of rats were defined: control, QR liposomes (QR-lipo), Co-Amox, and Co-Amox and QR-lipo. Liver injury severity in rats was evaluated for all groups through measurement of serum liver enzymes, liver antioxidant status, proinflammatory mediators, and microbiota modulation. The results revealed that QR-lipo reduced the severity of Co-Amox-induced hepatic damage in rats, as indicated by a reduction in serum liver enzymes and total liver antioxidant capacity. In addition, QR-lipo upregulated antioxidant transcription factors SIRT1 and Nrf2 and downregulated liver proinflammatory signatures, including IL-6, IL-1β, TNF-α, NF-κB, and iNOS, with upregulation in the anti-inflammatory one, IL10. QR-lipo also prevented Co-Amox-induced gut dysbiosis by favoring the colonization of Lactobacillus, Bifidobacterium, and Bacteroides over Clostridium and Enterobacteriaceae. These results suggested that QR-lipo ameliorates Co-Amox-induced liver damage by targeting SIRT1/Nrf2/NF-κB and modulating the microbiota.

Dose-Dependent Effect of Hydrogen Sulfide in Cyclophosphamide-Induced Hepatotoxicity in Rats.

Cyclophosphamide is a commonly used anticancer and immunosuppressive agent; however, hepatotoxicity is one of its severe toxicities. Hydrogen sulfide is a gaseous signaling molecule that plays crucial regulatory roles in various physiological functions. This study aimed to evaluate the hepatoprotective effect of hydrogen sulfide against cyclo phosp hamid e-ind uced hepatic damage in rats. Hepatotoxicity was induced by the single intraperitoneal administration of cyclophosphamide (200 mg/kg). Sprague-Dawley rats were treated by hydrogen sulfide donor, sodium hydrosulfide (25, 50, and 100 μmol/kg, intraperitoneal) 7 days before and 7 days after the administration of a single intraperitoneal injection of cyclophosphamide (200 mg/kg). Cyclo phosp hamide-ind uced hepatotoxicity was evaluated by serum and tissue biochemical and histopathological assessments. The levels of hydrogen sulfide, nitric oxide, cyclic guanosine monophosphate, interleukin 6, and interleukin 10 in liver homogenates were also determined by ELISA. One-way analysis of variance and Kruskal-Wallis tests were used as statistical analyses. Cyclophosphamide increased liver function enzymes (alanine aminotransferase and aspartate aminotransferase), immunoreactivity to caspase-3 and Apaf-1, and proinflammatory cytokines. Cyclophosphamide also induced histopathological alterations including pycnotic nucleus with eosinophilic cytoplasm, increased sinusoidal dilatation, congestion, and edema. Hydrogen sulfide cotreatment significantly reduced cyclo phosp hamid e-ind uced inflammation, histological alterations, and apoptosis in the liver. 50 mg/kg sodium hydrosulfide was more effective against cyclo phosp hamid e-ind uced hepatotoxicity. In conclusion, hydrogen sulfide with its anti-inflammatory and anti-apoptotic effects seems to be beneficial as an adjunct to cyclophosphamide treatment to reduce cyclo phosp hamid e-ind uced hepatotoxicity and thereby can be suggested as a promising agent to increase the therapeutic efficacy of cyclophosphamide.

Combined cerium and zinc oxide nanoparticles induced hepato-renal damage in rats through oxidative stress mediated inflammation

The toxicity profiles of nanoparticles (NPs) used in appliances nowadays remains unknown. In this study, we investigated the toxicological consequences of exposure to cerium oxide (CeO2) and zinc oxide (ZnO) nanoparticles given singly or in combination on the integrity of liver and kidney of male Wistar rats. Twenty (20) rats were allotted into four groups and treated as: Control (normal saline), CeO2NPs (50 μg/kg), ZnONPs (80 μg/kg) and [CeO2NPs (50 μg/kg) + ZnONPs (80 μg/kg)]. The nanoparticles were given to the animals through the intraperitoneal route, three times per week for four repeated weeks. Results revealed that CeO2 and ZnO NPs (singly) increased serum AST and ALT by 29% & 57%; 41% & 18%, and co-administration by 53% and 23%, respectively. CeO2 and ZnO NPs increased hepatic and renal malondialdehyde (MDA) by 33% and 30%; 38% and 67%, respectively, while co-administration increased hepatic and renal MDA by 43% and 40%, respectively. The combined NPs increased hepatic NO by 28%. Also, CeO2 and ZnO NPs, and combined increased BAX, interleukin-1β and TNF-α by 45, 38, 52%; 47, 23, 82% and 41, 83, 70%, respectively. Histology revealed hepatic necrosis and renal haemorrhagic parenchymal in NPs-treated rats. Summarily, CeO2 and ZnO NPs produced oxidative injury and induced inflammatory process in the liver and kidney of experimental animals.

Hepatoprotective activity of Averrhoa bilimbi leaf extract against Alcohol-induced liver damage in wistar rats

Averrhoa bilimbi is one of the India’s most legendary and sacred trees which belongs to the family Oxalidaceae.The aim of the current study is to examine the hepatoprotective effect of ethanolic leaf extracts of Averrhoa bilimbi against alcohol-induced hepatic damage in albino rats.The degree of protection was determined by evaluating biochemical parameters such as serum Alanine transaminase, Aspartate transaminase,Serum alkaline phosphatase, and total Bilirubin.The study reveals,when compared to the positive control, the leaf extract at dose levels of 100, 200, and 400mg/kg bodyweight p.o. showed a significant (P&lt;0.05) reduction in liver enzyme levels. The histopathological examination of liver sections were supported by these biochemical parameters. The phytochemical analysis of the extract shows the presence of phytosterols and flavonoids, which might be responsible for the hepatoprotective activity.Therefore it could be concluded that Averrhoa bilimbi leaves extract possess potent hepatoprotective activity against alcohol induced hepatic damage in rats.

Luteolin Mitigates Diabetic Dyslipidemia in Rats by Modulating ACAT-2, PPARα, SREBP-2 Proteins, and Oxidative Stress.

Diabetic dyslipidemia is a crucial link between type-2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular diseases (ASCVD). Natural biologically active substances have been advocated as complementary remedies for ASCVD and T2DM. Luteolin, a flavonoid, exhibits antioxidant, hypolipidemic, and antiatherogenic effects. Hence, we aimed to determine influence of luteolin on lipid homeostasis and hepatic damage in rats with T2DM induced by high-fat-diet (HFD) and streptozotocin (STZ). After being fed HFD for 10days, male Wistar rats received 40mg/kg STZ intraperitoneal injection on 11th day. Seventy-two hours later, hyperglycemic rats (fasting glucose > 200mg/dL) were randomized into groups, and oral hydroxy-propyl-cellulose, atorvastatin (5mg/kg), or luteolin (50mg/kg or 100mg/kg) administered daily, while continuing HFD for 28days. Luteolin significantly ameliorated dyslipidemia levels and concomitantly improved atherogenic index of plasma in a dose-dependent manner. Increased levels of malondialdehyde and diminished levels of superoxide dismutase, catalase, and glutathione in HFD-STZ-diabetic rats were significantly regulated by luteolin. Luteolin significantly intensified PPARα expression while decreasing expression of acyl-coenzyme A:cholesterol acyltransferase-2 (ACAT-2) and sterol regulatory element binding protein-2 (SREBP-2) proteins. Moreover, luteolin effectively alleviated hepatic impairment in HFD-STZ-diabetic rats to near-normal control levels. The findings of the present study expound mechanisms by which luteolin mitigated diabetic dyslipidemia and alleviated hepatic impairment in HFD-STZ-diabetic rats by amelioration of oxidative stress, modulation of PPARα expression, and downregulation of ACAT-2 and SREBP-2. In conclusion, our results imply that luteolin may be efficacious in management of dyslipidemia in T2DM, and future research may be essential to substantiate our findings.

Protective Effect of Herbal Medicinal Plant Extract against Carbon Tetrachloride Induced Liver Injury in Rat

Adiantum capillus (AC) Linn (Family: Adiantaceae) commonly known as “Hansraj” It is used in common cold, cough, pyrexia inflammation, acts as purgative. It improves digestion and renal function. This study was performed to investigate the hepato-defensive potential of Adiantum capillus in contradiction of carbon tetrachloride tempted hepatic damage in rats. The rodents were dosed with Acetonic extract (AEAC, 500mg/kg) extract of Adiantum capillus against Carbon Tetrachloride induced hepatic damage. Results shows thst Carbon Tetrachloride elevated the level of hepatic markers like SOPT, SGPT, bilirubin and ALP as well as altered the antioxidant enzymes. The level of hepatic biomarkers, as well as antioxidant enzyme, were recovered after the administration of at 500mg/kg, p.o., which was further confirmed by the histopathological. From above results it was concluded that The Acetonic extract (500 mg/kg, bw) extract of Adiantum capillus (ACE) recover the biochemical as well as antioxidant parameters, which were affected by Carbon Tetrachloride. The histopathological analysis supports the outcomes of antioxidants parameters.&#x0D; Key Words: Adiantum capillus, , , x, ,

Abstract 1212: Protocatechuic acid Abrogates Adriamycin-induced reproductive toxicities and hepatic damage in rats

Abstract 1212: Protocatechuic acid Abrogates Adriamycin-induced reproductive toxicities and hepatic damage in rats